Search results for: anticancer drugs

Authors: Soujanya Pasumarthi

Abstract:

Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

Procedia PDF Downloads 410

Authors: M. A. Sohaly, M. A. Elfouly

Abstract:

Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

Procedia PDF Downloads 99

Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

Abstract:

Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

Procedia PDF Downloads 450

Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

Abstract:

In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

Procedia PDF Downloads 150

Authors: Stanely Nsubuga

Abstract:

Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

Procedia PDF Downloads 98

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

Procedia PDF Downloads 26

Authors: Monika Szpringer, Aneta Pawlinska

Abstract:

Adverse childhood experiences are linked to various types of health and adapt problems at different stages of life. They include various types of abuse, neglect, and dysfunctional environment. They have an unfavorable impact on the development of a child and his future functioning in society. Adolescents who were exposed to bad treatment may suffer from health problems during adulthood, like chronic diseases, psychological disorders, drug addiction, and suicide attempts. Objective: The aim of the project is to assess the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs. Material And Methods: The research was carried out in the period from March to December 2018 in Mazowieckie, Świętokrzyskie, Łódzkie, and Lubelskie Voivodship. The group consisted of 600 people aged 16-18 (M=16,58; SD=0, 78), men (63,2%) aged 16-18 (M=16,60;SD= 0,78) and women (35,5%) aged 16-18 (M16,55;SD=0,79). Participants included residents from Youth Educational Centers and Youth Sociotherapy Centers. Each participant filled in Author's Questionnaire, Adverse Childhood Questionnaire, then Courtland Emotional Control Scale-CECS and Generalized Self Efficacy Scale-GSES. Results and conclusions: The most common adverse experiences, according to teenagers, were family abuse, divorce/separation/parent's death, overuse of alcohol or drugs by an inmate, and emotional neglect. Adolescents who suffered from five to twelve adverse experiences had a higher level of depression's control. Adverse childhood experiences have an importance for the level of anger and depression's control among teenagers taking drugs. The greatest importance of the level of anger's control has emotional neglect. A higher level of emotional neglect is linked to a lower ability to control anger. The greatest importance of the level of depression's control has physical abuse and emotional neglect. The higher physical abuse during childhood, and the higher frequency of emotional neglect, the bigger the depression's control. The sense of efficacy in the group of people who suffered from one to four adverse experiences is close to the sense of efficacy that suffered people from five to twelve adverse experiences. The most important factor lowering the sense of one's efficacy was the intensification of sexual abuse. It was confirmed that the intensification and frequency of adverse childhood experiences were higher among women than men. Women also characterized lower anger control and greater depression's control. The authors’ own analyses confirmed the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs.

Keywords: adolescences, adverse childhood experiences, coping with emotions, drugs

Procedia PDF Downloads 73

Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

Abstract:

Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

Procedia PDF Downloads 295

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

Abstract:

In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

Procedia PDF Downloads 273

Authors: Huafeng Wei

Abstract:

Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

Procedia PDF Downloads 150

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

Procedia PDF Downloads 25

Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

Abstract:

One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

Procedia PDF Downloads 63

Authors: Hassan M. Albishri, Fatimah Al-Shehri, Deia Abd El-Hady

Abstract:

Among the analytical techniques, reverse phase liquid chromatography (RPLC) is currently used in pharmaceutical industry. Ecofriendly analytical chemistry offers the advantages of decreasing the environmental impact with the advantage of increasing operator safety which constituted a topic of industrial interest. Recently, ionic liquids have been successfully used to reduce or eliminate the conventional organic toxic solvents. In the current work, a simple and ecofriendly ionic liquid modified RPLC (IL-RPLC) method has been firstly developed and compared with RPLC under acidic and neutral mobile phase conditions for simultaneous determination of atorvastatin-calcium, rosuvastatin and simvastatin. Several chromatographic effective parameters have been changed in a systematic way. Adequate results have been achieved by mixing ILs with ethanol as a mobile phase under neutral conditions at 1 mL/min flow rate on C18 column. The developed IL-RPLC method has been validated for the quantitative determination of drugs in pharmaceutical formulations. The method showed excellent linearity for analytes in a wide range of concentrations with acceptable precise and accurate data. The current IL-RPLC technique could have vast applications particularly under neutral conditions for simple and greener (bio)analytical applications of pharmaceuticals.

Keywords: ionic liquid, RPLC, anti-hyperlipidemic drugs, ecofriendly

Procedia PDF Downloads 226

Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

Abstract:

Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

Procedia PDF Downloads 66

Authors: Farhad Fakoursevom

Abstract:

Heart disease is one of the diseases which is found in abundance today. Various types of surgeries, such as bypasses, angiography, angioplasty, etc., are used to treat patients. People may receive such surgeries, some of which are invasive and some non-invasive, throughout their lives. People might cope with pre-surgery anxiety and stress, which can disrupt their normal life and even reduce the effects of the surgery, so the desired result can not be achieved in surgery. Considering this issue, the present study aimed to do a comparative assessment of people who received sedatives before surgery and people who did not receive sedatives. In terms of the purpose, this is an applied research and descriptive survey in terms of method. The statistical population included patients who underwent surgeries in the specialist heart hospitals of Mashhad, Iran; 60 people were considered as a statistical population, 30 of them received sedatives before surgery, and 30 others had not received sedatives before surgery. Valid and up-to-date articles were systematically used to collect theoretical bases, and a researcher-made questionnaire was used to examine the level of stress and anxiety of people. The questionnaire content validity was assessed by a panel of experts in psychology and medicine. The construct validity was tested using the software. Cronbach's alpha and composite reliability were used for reliability, which shows the appropriate reliability of the questionnaire. SPSS software was used to compare the research results between two groups, and the research findings showed that there is no significant association between the people who received sedatives and those who did not receive sedatives in terms of the amount of stress and anxiety. The longer the time of taking the drugs before the surgery, the more the mental peace of the patients will be. According to the results, it can be said that if we don't need to have an emergency operation and need more time, we have to use sedative drugs with different doses compared to the severity of the surgery, and also in case of a medical emergency such as heart surgery due to a stroke, we have to take advantage of psychological services during and before the operation and sedative drugs so that the patients can control their stress and anxiety and achieve better outcomes.

Keywords: sedative drugs, stress, anxiety, surgery

Procedia PDF Downloads 74

Authors: Jin Boo Jeong

Abstract:

In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

Procedia PDF Downloads 287

Authors: Husham Bayazed

Abstract:

A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

Procedia PDF Downloads 31

Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Alireza Mahmoudi Nasab, Tim Bakker

Abstract:

Introduction: Mycobacterium tuberculosis (MTB) is the most intelligent bacterium that existed in the world to our best knowledge. This bacterium can cause tuberculosis (TB) which is responsible for its spread speed and murder of millions of people around the world. MTB has the practical function to escape from anti-tuberculosis drugs (AT), for this purpose, it handles some mutations in the main genes and creates new patterns for inhibited genes. Method and materials: Researchers have their best tries to safely isolate MTB from the sputum specimens of 35 patients in some hospitals in the Tehran province and detect MTB by culture on Löwenstein-Jensen (LJ) medium and microscopic examination. DNA was extracted from the established bacterial colony by enzymatic extraction method. It was amplified by the polymerase chain reaction (PCR) method, reverse hybridization, and evaluation for detection of resistance genes; generally, researchers apply GenoType MTBDRplus assay. Results: Investigations of results declare us that 21 of the isolated specimens (about 60%) have mutation in rpoB gene, which resisted to rifampicin (most prevalence), and 8 of them (about 22.8%) have mutation in katG or inhA genes which resisted to isoniazid. Also, 4 of them (about 11.4%) don't have any mutation, and 2 of them (about 5.7%) have mutation in every three genes, which makes them resistant to the two drugs mentioned above. Conclusion: Rifampicin and isoniazid are two essential AT that using in the first line of treatment. Resistance in rpoB, and katG, and inhA genes related to mentioned drugs lead to ineffective treatment.

Keywords: mycobacterium tuberculosis, tuberculosis, drug resistance, isoniazid, rifampicin

Procedia PDF Downloads 58

Authors: Rosa L. Figueroa, Joselyn A. Hernández

Abstract:

During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

Procedia PDF Downloads 204

Authors: Mayank, Navneet Kaur, Narinder Singh

Abstract:

The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

Procedia PDF Downloads 93

Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama

Abstract:

Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.

Keywords: algae, analgesic drug, daphnia magna, toxicity

Procedia PDF Downloads 45

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

Abstract:

Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

Procedia PDF Downloads 148

Authors: S. Abd Rahim, F. A. Rahman, E. M. Nasir, N. A. Ramle

Abstract:

Co-crystal is believed to improve the solubility and dissolution rates and thus, enhanced the bioavailability of poor water soluble drugs particularly during the oral route of administration. With the existing of poorly soluble drugs in pharmaceutical industry, the screening of co-crystal formation using carbamazepine (CBZ) as a model drug compound with dicarboxylic acids co-crystal formers (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has been studied. The co-crystal formations were studied by varying the mol ratio values of CCF to CBZ to access the effect of CCF concentration on the formation of the co-crystal. Solvent evaporation, slurry, and cooling crystallisations which representing the solution based method co-crystal screening were used. The product crystal from the screening was characterized using X-ray powder diffraction (XRPD). The XRPD pattern profile analysis has shown that the CBZ co-crystals with FA and SA were successfully formed for all ratios studied. The findings revealed that CBZ-FA co-crystal were formed in two different polymorphs. It was found that CBZ-FA form A and form B were formed from evaporation and slurry crystallisation methods respectively. On the other hand, in cooling crystallisation method, CBZ-FA form A was formed at lower mol ratio of CCF to CBZ and vice versa. This study disclosed that different methods and mol ratios during the co-crystal screening can affect the outcome of co-crystal produced such as polymorphic forms of co-crystal and thereof. Thus, it was suggested that careful attentions is needed during the screening since the co-crystal formation is currently one of the promising approach to be considered in research and development for pharmaceutical industry to improve the poorly soluble drugs.

Keywords: co-crystal, dicarboxylic acid, carbamazepine, industry

Procedia PDF Downloads 329

Authors: Amir Saber Gharamaleki, Beitollah Alipour, Zeinab Faghfoori, Ahmad YariKhosroushahi

Abstract:

Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.

Keywords: anticancer, anti-proliferative, apoptosis, cytotoxicity, yeast

Procedia PDF Downloads 299

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

Procedia PDF Downloads 428

Authors: Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe

Abstract:

Helix aspersa, 'the garden snail' is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species in the west of Algeria. It is commonly used in zootherapy to purify blood and to treat cardiovascular diseases and liver problems. The aim of our study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa prepared by the traditional method on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). The cytotoxic effect of H. aspersa extract against Hs578T cells was evaluated by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)) while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. The level of TNFα has also measured in cell medium by ELISA method. The results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can reduce DPPH radical and ferric ion. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that TNFα induced necrosis is the main form of cell death induced by the extract. In conclusion, the present study may open new perspectives in the search for new natural anticancer drugs.

Keywords: breast cancer, Helix aspersa, Hs578t cell line, necrosis

Procedia PDF Downloads 388

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

Abstract:

Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

Procedia PDF Downloads 104

Authors: Itti Bist, Snehasis Bhakta, Di Jiang, Tia E. Keyes, Aaron Martin, Robert J. Forster, James F. Rusling

Abstract:

DNA damage from metabolites of lipophilic drugs and pollutants, generated by enzymes, represents a major toxicity pathway in humans. These metabolites can react with DNA to form either 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is the oxidative product of DNA or covalent DNA adducts, both of which are genotoxic and hence considered important biomarkers to detect cancer in humans. Therefore, detecting reactions of metabolites with DNA is an effective approach for the safety assessment of new chemicals and drugs. Here we describe a novel electrochemiluminescent (ECL) sensor array which can detect DNA oxidation and chemical DNA damage in a single array, facilitating a more accurate diagnostic tool for genotoxicity screening. Layer-by-layer assembly of DNA and enzyme are assembled on the pyrolytic graphite array which is housed in a microfluidic device for sequential detection of two type of the DNA damages. Multiple enzyme reactions are run on test compounds using the array, generating toxic metabolites in situ. These metabolites react with DNA in the films to cause DNA oxidation and chemical DNA damage which are detected by ECL generating osmium compound and ruthenium polymer, respectively. The method is further validated by the formation of 8-oxodG and DNA adduct using similar films of DNA/enzyme on magnetic bead biocolloid reactors, hydrolyzing the DNA, and analyzing by liquid chromatography-mass spectrometry (LC-MS). Hence, this combined DNA/enzyme array/LC-MS approach can efficiently explore metabolic genotoxic pathways for drugs and environmental chemicals.

Keywords: biosensor, electrochemiluminescence, DNA damage, microfluidic array

Procedia PDF Downloads 335

Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: curcumin, solubility, supersaturation, precipitation inhibitor

Procedia PDF Downloads 326

Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

Abstract:

1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

Procedia PDF Downloads 406