Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9

Search results for: isatin and adamantane

9 Schiff Bases of Isatin and Admantane-1-Carbohydrazide: Synthesis, Characterization, and Anticonvulsant Activity

Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed


Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18–23). Then, their anticonvulsant activity was evaluated using a pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18–23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy, with compound 23 being the best. Interestingly, most of the synthesized molecules showed a reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.

Keywords: isatin and adamantane, anticonvulsant activity, PTZ-induced seizure, molecular docking

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8 A DFT-Based QSARs Study of Kovats Retention Indices of Adamantane Derivatives

Authors: Z. Bayat


A quantitative structure–property relationship (QSPR) study was performed to develop models those relate the structures of 65 Kovats retention index (RI) of adamantane derivatives. Molecular descriptors derived solely from 3D structures of the molecular compounds. The usefulness of the quantum chemical descriptors, calculated at the level of the DFT theories using 6-311+G** basis set for QSAR study of adamantane derivatives was examined. The use of descriptors calculated only from molecular structure eliminates the need to experimental determination of properties for use in the correlation and allows for the estimation of RI for molecules not yet synthesized. The prediction results are in good agreement with the experimental value. A multi-parametric equation containing maximum Four descriptors at B3LYP/6-31+G** method with good statistical qualities (R2train=0.913, Ftrain=97.67, R2test=0.770, Ftest=3.21, Q2LOO=0.895, R2adj=0.904, Q2LGO=0.844) was obtained by Multiple Linear Regression using stepwise method.

Keywords: DFT, adamantane, QSAR, Kovat

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7 An Organocatalytic Construction of Vicinal Tetrasubstituted Stereocenters via Mannich Reaction of 2-Substituted Benzofuran-3-One with Isatin-Derived Ketimine

Authors: Koilpitchai Sivamuthuraman, Venkitasamy Kesavan


3-substituted 3-amino-2-oxindole skeleton bearing adjacent tetrasubstituted stereogenic centers is of great importance because of these heterocyclic motifs possess a wide range of pharmacological activity. The catalytic asymmetric construction of multi functionalised heterocyclic compound with adjacent tetrasubstituted stereocenters is one of the most difficult tasks in organic synthesis. To date, the most straightforward methodologies have been developed for synthesis of chiral 3-substituted 3-amino-2-oxindoles through the addition of carbon nucleophiles to isatin-derived ketimines. However, only a few successful examples have been described for the assembly of vicinal tetrasubstituted stereocenters using isatin derived ketimines as electrophiles. On the other hand, 2,2-Disubstituted benzofuran-3(2H)-ones and related frameworks are characteristic of a quaternary stereogenic center at C2 position present in quite a number of natural products and bioactive Molecules.Despite the intensive efforts devoted for the construction of 2,2-Disubstituted Benzofuran-3[2H]-one, there are only a few asymmetric methods such as organocatalytic Michael addition and enantioselective halogenations were reported till now. Due to the biological importance of oxindole and benzofuran-3-one, it is proposed here with the synthesis of hybrid molecule containing tetrasubstituted stereo centers through asymmetric organocatalysis. The addition of 2-substituted Benzofuran-3-one(1a) to isatin-derived ketimines(2a) using a bifunctional organocatalyst(catalyst IV or V), leading to chiral heterocyclic compounds containing both 3-amino 2-oxindole and benzofurn-3-one bearing vicinal quaternary stereocenters with good yields and excellent enantioselectivity. The present study extends the scope of the catalytic asymmetric Mannich reaction with isatin-derived ketimines, providing a new class of amino oxindole derivatives having benzofuran-3-one.

Keywords: asymmetric synthesis, benzofuran-3-one, isatin-derived ketimines, quaternary stereocenters

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6 Exploring the Bifunctional Organocatalysts for Asymmetric Synthesis of 3-Substituted-3-Aminooxindoles

Authors: Jasneet Kaur, Swapandeep Singh Chimni


The unfavorable use of metal-based catalysts that are often extortionate and toxic can be overcome by using small organic molecules known as organocatalysts. A variety of small organic molecules, including Brønsted/Lewis bases and acids, based on sulfonic acids, phosphoric acids, amines, phosphines or carbenes, Cinchona alkaloids, have been used as organocatalysts. One of the key reasons for using organocatalysis is their ability to be effectively removed from the final product in comparison to the metallic counterparts, which are exceedingly difficult to remove. The present investigation seeks to explore the catalytic nature of Cinchona alkaloids as an organocatalyst for enantioselective synthesis of 3-substituted-3-aminooxindole, which is known to exhibit a variety of biological activities and pharmacological activities. In this context, an organocatalytic asymmetric route for the synthesis of 3-aminooxindoles via reaction of isatin imine with α-acetoxy-β-ketoesters has been developed. The bifunctional Cinchona derived thiourea catalyzed the reaction of α-acetoxy-β-ketoesters derivatives with isatin imine to afford 3-substituted-aminooxindole derivatives in up to 93% yield, 95% enantiomeric excess and >20:1 diastereomeric ratio. The reaction was performed at room temperature for two hours using 10 mol% of catalyst, in the presence of 4Å molecular sieves in tetrahydrofuran as a solvent at ambient temperature. After the completion of the reaction, the pure product could be easily separated by using column chromatography using hexane and ethyl acetate as solvents. In conclusion, the catalytic potential of Cinchona derived chiral thiourea-tertiary amine catalyst was explored for an organocatalytic enantioselective Mannich reaction of β-ketoester derivatives with various isatin imine derivatives under mild conditions.

Keywords: asymmetric synthesis, aminooxindoles, enantioselective, isatin imine

Procedia PDF Downloads 38
5 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Authors: Harish Rajak, Kamlesh Raghuwanshi


Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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4 Synthesis and Analgesic activity of 2-(p-Substituted phenyl)-3-[4-(N-Substituted amino) methyl-2-oxo indoilin-3-ylidene]benzenesulfonyl Quinazolin-4(3H)-One Derivatives

Authors: N. Gopal, K. Jaasminerjiit, L. Z. Xiang


Quinazoline-4(3H)-one ring system has been consistently regarded as promising privileged structural icon owing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occurring alkaloids. The literature reveals that 2nd & 3rd positions of the quinazolin-4(3H)-one pharmacophore are the target for substitution with other moieties. On the other hand, sulphanilamide derivatives and isatin moiety also displayed valuable biological activities. Hence, it was thought worthwhile to study the effects of three pharmacophoric moieties like quinazolinone, sulphanilamide and isatin in a single molecule for the better analgesic activity with lower toxicity. Series of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives have been synthesised from the intermediate Schiff base of 2-(4’-substitutedphenyl)-3-[(N-2-oxoindolin-3-ylidene)-4”-sulphonamidophenyl]-quinazolin-4(3H)-one derivatives, which was prepared from reacting 2-(substituted phenyl)-4H-benzo[d][1,3]-oxazin-4-one with sulphanilamide. The required benzoxazinone derivatives were prepared by reacting anthranilic acid with benzoyl chloride. All the compounds structure was characterised by using H1 NMR, IR and Mass spectroscopy. The intermediate Schiff base and final Mannich base compounds were evaluated for their analgesic activity by acetic acid-induced writhing method at the dose of 25mg/kg, 50 mg/kg, and 100 mg/kg (bw) and Diclofenac (25mg/kg of body weight) will be used as the reference drugs. From the results of the study, it has been observed that final Mannich base showed a better analgesic activity when compared to the parent Schiff bases, it was found that compound substituted with N-methyl piperazine at 1st position of the indole nucleus of the final quinazolinone derivatives (GA4B1) i.e. 2-(4’-methoxy phenyl)-3-[4-(N-(1-N-methyl piperazine amine) methyl-2-oxo indoilin-3-ylidene] benzenesulfonyl quinazolin-4(3H)-one increases the analgesic activity and among the synthesised compounds, GA4B1 exhibited quite superior analgesic activity. The remaining Schiff bases and Mannich base derivatives exhibited moderate analgesic activity. All the compounds showed a dose dependent activity. None of the synthesised compound showed ulcer index whereas the standard drug, diclofenac [25 mg/kg (bw)] showed significantly higher gross ulcer index values.

Keywords: analgesic activity, isatin, mannich base, quinazolin-4(3H)-one

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3 Preparation and Properties of Self-Healing Polyurethanes Utilizing the Host-Guest Interaction between Cyclodextrin and Adamantane Moieties

Authors: Kaito Sugane, Mitsuhiro Shibata


Self-healing polymers have attracted attention because their physical damage and cracks can be effectively repaired, thereby extending the lifetime of the materials. Self-healing polymers using host-guest interaction have the advantage that they are quickly repaired under mild temperature conditions when compared with self-healing polymer using dynamic covalent bonds such as Diels-Alder (DA)/retro-DA and disulfide metathesis reactions. Especially, it is known that hydrogels utilizing the host-guest interaction between cyclodextrin and various guest molecules are repeatedly self-repaired at room temperature. However, most of the works deal with hydrogels, and little attention has been paid for thermosetting resins as polyurethane, epoxy and unsaturated polyester resins. In this study, polyetherurethane networks (PUN-CD-Ads) incorporating cyclodextrin and adamantane moieties were prepared by the crosslinking reactions of β-cyclodextrin (CD), 1-adamantanol (AdOH), glycerol ethoxylate (GCE) and hexamethylene diisocyanate (HDI), and thermal, mechanical and self-healing properties of the polymer network films were investigated. Our attention was focused on the influences of molar ratio of CD/AdOH, GCE/CD and OH/NCO on the properties. The FT-IR, and gel fraction analysis revealed that the urethanization reaction smoothly progress to form polyurethane networks. When two cut pieces of the films were contacted at the cross-section at room temperature for 30 seconds, the two pieces adhered to produce a self-healed film. Especially, the PUN-CD-Ad prepared at GCE/CD = 5/1, CD/AdOH = 1/1, and OH/NCO = 1/1 film exhibited the highest healing efficiency for tensile strength. Most of the PUN-CD-Ads were successfully self-healed at room temperature.

Keywords: host-guest interaction, network polymer, polyurethane, self-healing

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2 Synthesis and Pharmacological Activity of Some Oxyindole Derivatives

Authors: Vivek Singh Bhadauria, Abhishek Pandey


Indole-2,3-diones are known for their various biological activities. By suitable control of a substituent, different novel indole-2,3-diones were synthesized. In this present study, various Schiff and Mannich bases were synthesized and characterized, and evaluated their for different pharmacological activities. The compounds were prepared by reacting indole-2,3-dione with benzyl chloride and 4-substituted thiosemicarbazides. All the synthesized compounds were characterized by the TLC, MP, Elemental analysis, FTIR, 1H-NMR and Mass spectroscopy. The compounds have been evaluated for their anticancer, antituberculosis, anticonvulsant, antiinflammatory as well as anti-SARS activity and the results are presented. Some of compounds possessed different pharmacological activity at a concentration of 200 mg/kg body weight and even at lower concentration.

Keywords: indoles, isatin, NMR, biological activities

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1 The Use of Actoprotectors by Professional Athletes

Authors: Kalin Ivanov, Stanislava Ivanova


Actoprotectors are substances with hight performance enchasing potential and hight antioxidant activity. Most of these drugs have been developed in USSR for military medicine purposes. Based on their chemical composition actoprotectors could be classified into three categories: benzimidazole derivatives (ethomersol, bemitil); adamantane derivatives (bromantane), other chemical classes. First data for intake of actoprotectors from professional athletes is from 1980. The daily intake of actoprotectors demonstrate many benefits for athletes like: positive effect on the efficiency of physical work, antihypoxic effects, antioxidant effects, nootropic effects, rapid recovery. Since 1997, bromantane is considered as doping. This is a result of Summer Olympic Games in Athlanta (1996) when several Russian athletes tested positive for bramantane. Even the drug is safe for athletes health its use is considered as violation of anti- doping rules. More than 37 years bemetil has been used by professional athletes with no risk but currently it is included in WADA monitoring programme for 2018. Current perspectives are that most used actoprotectors would be considered as doping. Many clinical studies have confirmed that intake of bemitil and bromantan demonstrate positive influence on the physical work capacity but data for other actoprotectors like chlodantane, ademol, ethomersol is limited.

Keywords: actoprotector, sport, doping, bemitil

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