Search results for: Sudipto Chakraborty

Authors: Ronit Chakraborty

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Kolkata, formerly known as Calcutta, is the capital of West Bengal state and the former capital of India (1722-1911) of British India. Located at the heart of Hugli river (one of the main channels of Ganges river), the city is the heart of the state, which forms a base for commerce, transport and manufacture. The large and vibrant city thrives amidst the economic, social and political issues arising from the pages of history to the contemporary times. The unique nature, grandeurs, public debates on tea-stalls and obviously the charismatic scenic beauty and heritage keep the city to be criticized in all horizons, across the world. Movies in India are a big source of knowledge, which can be used as a powerful tool for political mobilization and to indirectly communicate with voters since cinema can be used as a tool of propaganda as it has a wide range of public interests. History proves the fact that films produced in India have been apt enough in making public interests be deeply portrayed through their content in a versatile manner. Such is the portrayal of India’s first capital, Kolkata and its ultimate truth being organizingly laid over by the trilogy of two international fame directors-Mrinal Sen and Satyajit Ray, through their ‘magnum opus- the ‘Kolkata trilogy’. Mrinal Sen’s Interview(1971), Calcutta 71(1972), Padatik(The Guerilla Fighter)(1973) and Satyajit Ray’s Pratidwandi (The Adversary)(1970), Seemabaddha(Company Limited)(1971), Jana Aranya(1976). These films picturized the contemporary Kolkata trends, issues and crises arising amidst the political set-up both by the positive and negative variables attributing to the day-to-day happenings of the city. The movies have been set amidst the turmoil that the nation was going through during Indira Gandhi’s declaration of Emergency, resulting from the general sense of disillusionment that prevailed during that time. Ray wasn't affiliated to any political party and his films largely contributed towards the contemporary conditions prevailing in the society. Mrinal Sen, being a Marxist was in constant search of the bitter truth that the society had to offer through his lens under the prevailing darkness through his trilogy. The research paper attempts to widely view and draw a comparative study of the overall description of the city of Kolkata as portrayed by Sen and Ray in their respective trilogies. By the usage of the visual content analysis method, the researcher has explored the six movies; both the trilogies of Mrinal Sen and Satyajit Ray and tried to analyse the differences as well as the similarities pertaining to understand India’s first capital city Kolkata in various dimensions along with its circumference.

Keywords: Kolkata, trilogy, Satyajit Ray, Mrinal Sen, films, comparative study

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Authors: B. D. Patni, Ashwani Jain, Arindom Chakraborty

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The world’s highest mountain range has been forming since the collision of Indian Plate with Asian Plate 40-50 million years ago. The Indian subcontinent has been deeper and deeper in to the rest of Asia resulting upliftment of Himalaya & Tibetan Plateau. The complex domain has become a major challenge for construction of hydro electric projects. The Himalayas are geologically complex & seismically active. Shifting of Indian Plate northwardly and increasing the amount of stresses in the fragile domain which leads to deformation in the form of several fold, faults and upliftment. It is difficult to undergo extensive geological investigation to ascertain the geological problems to be encountered during construction. Inaccessibility of the terrain, high rock cover, unpredictable ground water condition etc. are the main constraints. The hydroelectric projects located in Himalayas have faced many geological and geo-hydrological problems while construction of surface and subsurface works. Based on the experience, efforts have been made to identify the expected geological problems during and after construction of the projects. These have been classified into surface and subsurface problems which include existence of inhomogeneous deep overburden in the river bed or buried valley, abrupt change in bed rock profile, Occurrences of fault zones/shear zones/fractured rock in dam foundation and slope instability in the abutments. The tunneling difficulties are many such as squeezing ground condition, popping, rock bursting, high temperature gradient, heavy ingress of water, existence of shear seams/shear zones and emission of obnoxious gases. However, these problems were mitigated by adopting suitable remedial measures as per site requirement. The support system includes shotcrete, wire mesh, rock bolts, steel ribs, fore-poling, pre-grouting, pipe-roofing, MAI anchors, toe wall, retaining walls, reinforced concrete dowels, drainage drifts, anchorage cum drainage shafts, soil nails, concrete cladding and shear keys. Controlled drilling & blasting, heading & benching, proper drainage network and ventilation system are other remedial measures adopted to overcome such adverse situations. The paper highlights the geological uncertainties and its remedial measures in Himalaya, based on the analysis and evaluation of 20 hydroelectric projects during construction.

Keywords: geological problems, shear seams, slope, drilling & blasting, shear zones

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Authors: Manali Chakraborty

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In the developing countries the most prevalent pathological state is malnutrition and under nutrition due to deficiency of essential nutrients. This condition is more seen between the woman population, especially in the adolescent girls. It is causing childhood deaths along with others cognitive, degenerative diseases. Born of low weight babies and stillbirth are also major problems associated with the malnutrition. Along with the increased level of population, people not only should concern about their quantity of food but also for the quality of the food to be healthy. Lethargy, depression caused due to iron deficiency often quoted as normal or unimportant issues. Children of malnourished women are more likely associated with cognitive impairment, immune dysfunction leading to a higher risk of being attacked by diseases. Malnourishment also affects the productivity of women. Low social status, lack of proper nutritional education is an important cause of this nutrient deficiency among women. Iron deficiency and anemia are mostly famous nutritional deficiencies among women worldwide. Mostly women from below poverty lined area are anemic due to less consumption of iron-rich foods or having foods that might inhibit the iron absorption. Growing females like adolescents or lactating females need more iron supply. Less supplement causes iron deficiency. Though malaria also might cause anemia, it is more likely endemic one in some specific areas. Folate deficiency in females also may cause neurological defects in the infants. Other Vitamin B, A deficiencies along with low iodine level is also noted in malnourished women. According to tradition, still in some areas in developing countries females have their food at the end. According to some survey and collected data, these females are often into the risk zone of being malnourished. Regularly they have the very lesser amount, or food sometimes may start to lose its nutrients. Women are the one who maintains the responsibility to cook foods in the home. Lack of proper nutritional education and proper food preparation not only make those foods lose the nutrients leading to impairment in proper nutrient intake of the family members but also impairing own nutritional status. Formulation and development of food products from iron or other nutrient affluent sources viz., traditional herbs can be helpful in the prevention of such malnutrition condition in females. Keeping low cost and smooth maintenance of the food product development from the natural sources like pulses, cereals or other vegetation also can be beneficial to sustain socio-economic condition. Consumption of such kind of foodstuff is much healthier rather than taking continuous supplements like capsules. Utilization of proper scientific and cost-effective techniques for this food product development and their distribution among rural women population might be an enormous initiative.

Keywords: anemia, food supplements, malnutrition, rural places, women population

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Authors: Devendra Kumar Pandey, Debabrata Chakraborty

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The advancement in various concrete ingredients like plasticizers, additives and fibers, etc. has enabled concrete technologists to develop many viable varieties of special concretes in recent decades. Such various varieties of concrete have significant enhancement in green as well as hardened properties of concrete. A prudent selection of appropriate type of concrete can resolve many design and application issues in construction projects. This paper focuses on usage of self-compacting concrete, high early strength concrete, structural lightweight concrete, fiber reinforced concrete, high performance concrete and ultra-high strength concrete in the structures. The modified properties of strength at various ages, flowability, porosity, equilibrium density, flexural strength, elasticity, permeability etc. need to be carefully studied and incorporated into the design of the structures. The paper demonstrates various mixture combinations and the concrete properties that can be leveraged. The selection of such products based on the end use of structures has been proposed in order to efficiently utilize the modified characteristics of these concrete varieties. The study involves mapping the characteristics with benefits and savings for the structure from design perspective. Self-compacting concrete in the structure is characterized by high shuttering loads, better finish, and feasibility of closer reinforcement spacing. The structural design procedures can be modified to specify higher formwork strength, height of vertical members, cover reduction and increased ductility. The transverse reinforcement can be spaced at closer intervals compared to regular structural concrete. It allows structural lightweight concrete structures to be designed for reduced dead load, increased insulation properties. Member dimensions and steel requirement can be reduced proportionate to about 25 to 35 percent reduction in the dead load due to self-weight of concrete. Steel fiber reinforced concrete can be used to design grade slabs without primary reinforcement because of 70 to 100 percent higher tensile strength. The design procedures incorporate reduction in thickness and joint spacing. High performance concrete employs increase in the life of the structures by improvement in paste characteristics and durability by incorporating supplementary cementitious materials. Often, these are also designed for slower heat generation in the initial phase of hydration. The structural designer can incorporate the slow development of strength in the design and specify 56 or 90 days strength requirement. For designing high rise building structures, creep and elasticity properties of such concrete also need to be considered. Lastly, certain structures require a performance under loading conditions much earlier than final maturity of concrete. High early strength concrete has been designed to cater to a variety of usages at various ages as early as 8 to 12 hours. Therefore, an understanding of concrete performance specifications for special concrete is a definite door towards a superior structural design approach.

Keywords: high performance concrete, special concrete, structural design, structural lightweight concrete

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Sukalyan Chakraborty

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Arsenic contamination in groundwater has been a matter of serious concern worldwide. Globally, arsenic contaminated water has caused serious chronic human diseases and in the last few decades the transfer of arsenic to human beings via food chain has gained much attention because food represents a further potential exposure pathway to arsenic in instances where crops are irrigated with high arsenic groundwater, grown in contaminated fields or cooked with arsenic laden water. In the present study, the groundwater of Sahibganj district of Jharkhand has been analysed to find the degree of contamination and its probable associated risk due to direct consumption or irrigation. The present study area comprising of three blocks, namely Sahibganj, Rajmahal and Udhwa in Sahibganj district of Jharkhand state, India, situated in the western bank of river Ganga has been investigated for arsenic contamination in groundwater, soil and crops predominantly growing in the region. Associated physicochemical parameters of groundwater including pH, temperature, electrical conductivity (EC), total dissolved solids (TDS), dissolved oxygen (DO), oxidation reduction potential (ORP), ammonium, nitrate and chloride were assessed to understand the mobilisation mechanism and chances of arsenic exposure from soil to crops and further into the food chain. Results suggested the groundwater to be dominantly Ca-HCO3- type with low redox potential and high total dissolved solids load. Major cations followed the order of Ca ˃ Na ˃ Mg ˃ K. The concentration of major anions was found in the order of HCO3− > Cl− > SO42− > NO3− > PO43− varied between 0.009 to 0.20 mg L-1. Fe concentrations of the groundwater samples were below WHO permissible limit varying between 54 to 344 µg L-1. Phosphate concentration was high and showed a significant positive correlation with arsenic. As concentrations ranged from 7 to 115 µg L-1 in premonsoon, between 2 and 98 µg L-1 in monsoon and 1 to 133µg L-1 in postmonsoon season. Arsenic concentration was found to be much higher than the WHO or BIS permissible limit in majority of the villages in the study area. Arsenic was also seen to be positively correlated with iron and phosphate. PCA results demonstrated the role of both geological condition and anthropogenic inputs to influence the water quality. Arsenic was also found to increase with depth up to 100 m from the surface. Calculation of carcinogenic and non-carcinogenic effects of the arsenic concentration in the communities exposed to the groundwater for drinking and other purpose indicated high risk with an average of more than 1 in a 1000 population. Health risk analysis revealed high to very high carcinogenic and non-carcinogenic risk for adults and children in the communities dependent on groundwater of the study area. Observation suggested the groundwater to be considerably polluted with arsenic and posing significant health risk for the exposed communities. The mobilisation mechanism of arsenic also could be identified from the results suggesting reductive dissolution of Fe oxyhydroxides due to high phosphate concentration from agricultural input arsenic release from the sediments along river Ganges.

Keywords: arsenic, physicochemical parameters, mobilisation, health effects

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Authors: Kaomud Tyagi, Rajasree Chakraborty, Shantanu Kundu, Devkant Singha, Kailash Chandra, Vikas Kumar

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The melon thrips, Thrips palmi is a serious pest of a wide range of agriculture crops and also act as vectors for plant viruses (genus Tospovirus, family Bunyaviridae). More molecular data on this species is required to understand the cryptic speciation and evolutionary affiliations. Mitochondrial genomes have been widely used in phylogenetic and evolutionary studies in insect. So far, mitogenomes of five thrips species (Anaphothrips obscurus, Frankliniella intonsa, Frankliniella occidentalis, Scirtothrips dorsalis and Thrips imaginis) is available in the GenBank database. In this study, we sequenced the first complete mitogenome T. palmi and compared it with available thrips mitogenomes. We assembled the mitogenome from the whole genome sequencing data generated using Illumina Hiseq2500. Annotation was performed using MITOS web-server to estimate the location of protein coding genes (PCGs), transfer RNA (tRNAs), ribosomal RNAs (rRNAs) and their secondary structures. The boundaries of PCGs and rRNAs was confirmed manually in NCBI. Phylogenetic analyses were performed using the 13 PCGs data using maximum likelihood (ML) in PAUP, and Bayesian inference (BI) in MrBayes 3.2. The complete mitogenome of T. palmi was 15,333 base pairs (bp), which was greater than the genomes of A. obscurus (14,890bp), F. intonsa (15,215 bp), F. occidentalis (14,889 bp) and S. dorsalis South Asia strain (SA1) (14,283 bp), but smaller than the genomes of T. imaginis (15,407 bp) and S. dorsalis East Asia strain (EA1) (15,343bp). Like in other thrips species, the mitochondrial genome of T. palmi was represented by 37 genes, including 13 PCGs, large and small ribosomal RNA (rrnL and rrnS) genes, 22 transfer RNA (tRNAs) genes (with one extra gene for trn-Serine) and two A+T-rich control regions (CR1 and CR2). Thirty one genes were observed on heavy (H) strand and six genes on the light (L) strand. The six tRNA genes (trnG,trnK, trnY, trnW, trnF, and trnH) were found to be conserved in all thrips species mitogenomes in their locations relative to a protein-coding or rRNA gene upstream or downstream. The gene arrangements of T. palmi is very close to T. imaginis except the rearrangements in tRNAs genes: trnR (arginine), and trnE (glutamic acid) were found to be located between cox3 and CR2 in T. imaginis which were translocated between atp6 and CR1 in T. palmi; trnL1 (Leucine) and trnS1(Serine) were located between atp6 and CR1 in T. imaginis which were translocated between cox3 and CR2 in T. palmi. The location of CR1 upstream of nad5 gene was suggested to be ancestral condition of the thrips species in subfamily Thripinae, was also observed in T. palmi. Both the Maximum likelihood (ML) and Bayesian Inference (BI) phylogenetic trees generated resulted in similar topologies. The T. palmi was clustered with T. imaginis. We concluded that more molecular data on the diverse thrips species from different hierarchical level is needed, to understand the phylogenetic and evolutionary relationships among them.

Keywords: thrips, comparative mitogenomics, gene rearrangements, phylogenetic analysis

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: Mandeep Singh Azad.Dibyendu Chakraborty, Vikas Vohra

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Introduction: Poonch is one of the remotest districts of the Jammu and Kashmir (UT) and situated on international borders. This native poultry population in these areas is quite hardy and thrives well in adverse climatic conditions. Till date, no local breed from this area (Jammu Province) has been characterized thus present study was undertaken with the main objectives of molecular characterization of ChB6 gene in local native chicken of Poonch region located at international borders between India and Pakistan. The chicken B-cell marker (ChB6) gene has been proposed as a candidate gene in regulating B-cell development. Material and Method: RNA was isolated by Blood RNA Purification Kit (HiPura) and Trizol method from whole blood samples. Positive PCR products with size 1110 bp were selected for further purification, sequencing and analysis. The amplified PCR product was sequenced by Sangers dideoxy chain termination method. The obtained sequence of ChB6 gene of Poonchi chicken were compared by MEGAX software. BioEdit software was used to construct phylogenic tree, and Neighbor Joining method was used to infer evolutionary history. In order to compute evolutionary distance Maximum Composite Likelihood method was used. Results: The positively amplified samples of ChB6 genes were then subjected to Sanger sequencing with “Primer Walking. The sequences were then analyzed using MEGA X and BioEdit software. The sequence results were compared with other reported sequence from different breed of chicken and with other species obtained from the NCBI (National Center for Biotechnology Information). ClustalW method using MEGA X software was used for multiple sequence alignment. The sequence results of ChB6 gene of Poonchi chicken was compared with Centrocercus urophasianus, G. gallus mRNA for B6.1 protein, G. gallus mRNA for B6.2, G. gallus mRNA for B6.3, Gallus gallus B6.1, Halichoeres bivittatus, Miniopterus fuliginosus Ferringtonia patagonica, Tympanuchus phasianellus. The genetic distances were 0.2720, 0.0000, 0.0245, 0.0212, 0.0147, 1.6461, 2.2394, 2.0070 and 0.2363 for ChB6 gene of Poonchi chicken sequence with other sequences in the present study respectively. Sequencing results showed variations between different species. It was observed that AT content were higher then GC content for ChB6 gene. The lower AT content suggests less thermostable. It was observed that there was no sequence difference within the Poonchi population for ChB6 gene. The high homology within chicken population indicates the conservation of ChB6 gene. The maximum difference was observed with Miniopterus fuliginosus (Eastern bent-wing bat) followed by Ferringtonia patagonica and Halichoeres bivittatus. Conclusion: Genetic variation is the essential component for genetic improvement. The results of immune related gene Chb6 shows between population genetic variability. Therefore, further association studies of this gene with some prevalent diseases in large population would be helpful to identify disease resistant/ susceptible genotypes in the indigenous chicken population.

Keywords: ChB6, sequencing, ClustalW, genetic distance, poonchi chicken, SNP

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Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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