Anupam G. Banerjee

Design, synthesis, and anticonvulsant screening of some substituted piperazine and aniline derivatives of 5-phenyl-oxazolidin-2,4-diones and 5,5-diphenylimidazolidin-2,4 diones

Substituted piperazine and aniline derivatives of oxazolidin-2,4-diones and imidazolidin-2,4-diones were synthesized by N3 alkylation and screened for their anticonvulsant activity by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test. Among all the synthesized derivatives, compounds 4b, 6c, 6d, 10b, 11a, 11b, and 11d were found to exhibit maximum seizure protection in MES test and were devoid of any neurotoxic effects. Furthermore, the functional activity of these compounds were evaluated in vivo for 5-HT1A receptor affinity by using rectal body temperature and lower lip retraction in rats, while head twitch response in mice was performed for the determination of probable affinity toward 5-HT2A receptor. The results of these tests demonstrated that compounds 4b, 6c, 6d, 10b, 11a, 11b, and 11d exhibited 5-HT1A (pre- and postsynaptic) agonist/antagonist features whereas compounds 11a and 11b exhibited antagonist action for 5-HT2A receptor. From the in vivo studies it was observed that a majority of aniline derivatives (6c, 6d, 11a, 11b, 11d) were found to be more active as compared to their bulky piperazine congeners (4b, 10b). Thus, the overall reduction in the bulkiness of the derivatives without compromising the lipophilicity is well appreciated for providing insights into the structural requirements necessary for development of new effective molecules having anticonvulsant effect.

Design, synthesis, evaluation and molecular modelling studies of some novel 5,6-diphenyl-1,2,4-triazin-3(2H)-ones bearing five-member heterocyclic moieties as potential COX-2 inhibitors: A hybrid pharmacophore approach

A series of novel hybrids comprising of 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole tethered to 5,6-diphenyl-1,2,4-triazin-3(2H)-one were designed, synthesised and evaluated as COX-2 inhibitors for the treatment of inflammation. The synthesised hybrids were characterised using FT-IR, 1H NMR, 13C NMR, elemental (C,H,N) analyses and assessed for their anti-inflammatory potential by in vitro albumin denaturation assay. Compounds exhibiting activity comparable to indomethacin and celecoxib were further evaluated for in vivo anti-inflammatory activity. Oral administration of promising compounds 3c-3e and 4c-4e did not evoke significant gastric, hepatic and renal toxicity in rats. These potential compounds exhibited reduced malondialdehyde (MDA) content on the gastric mucosa suggesting their protective effects by inhibition of lipid peroxidation. Based on the outcome of in vitro COX assay, compounds 3c-3e and 4c-4e (IC50 0.60-1.11μM) elicited an interesting profile as competitive selective COX-2 inhibitors. Further, selected compounds 3e and 4c were found devoid of cardiotoxicity post evaluation on myocardial infarcted rats. The in silico binding mode of the potential compounds into the COX-2 active site through docking and molecular dynamics exemplified their consensual interaction and subsequent COX-2 inhibition with significant implications for structure-based drug design.

Green route synthesis of 4-thiazolidinone analogs of isonicotinic acid hydrazide

Abstract The broad and potent activity of 4-thiazolidinones has established it as one of the biologically important scaffolds. The synthesis of N-(2-aryl-4-oxothiazolidin-3-yl)isonicotinamide by a novel method of stirring and sonication is described. The conventional method for synthesis of 4-thiazolidinones involves use of a Dean-Stark water separator for the removal of water from the reaction with long reaction times (12–48 h), and the stirring procedure also involves the use of DCC (dicyclohexylcarbodiimide) as a dehydrating agent. We report the synthesis of 4-thiazolidinone analogs of isonicotinic acid hydrazide by novel, green route methods of sonication and stirring using molecular sieves. Results indicate that high yields and shorter reaction times can be achieved by employing novel green route methods of synthesis.

Eco-friendly synthesis of 2-azetidinone analogs of isonicotinic acid hydrazide

Abstract 2-Azetidinones possess broad and potent activity due to presence of β-lactam ring and has been established as one of the biologically important scaffolds. The synthesis of N-(4-aryl-2-oxoazetidinone)-isonicotinamide by novel methods of stirring and sonication are described. The conventional method for synthesis of 2-azetidinones involves use of Dean–Stark water separator for the removal of water from the reaction with long reaction time (12–16 h reflux) at a very low temperature (−70 to −90°C). The microwave method reported requires inert atmosphere of nitrogen gas for the synthesis of 2-azetidinones. We report herein the synthesis of 2-azetidinone analogs of isonicotinic acid hydrazide by novel green route methods of sonication and stirring using molecular sieves. Results indicate that higher yields and shorter reaction times can be achieved by employing novel green route methods of synthesis.

Design, Synthesis and Pharmacological Evaluation of N3 Aryl/ Heteroaryl Substituted 2-((Benzyloxy and Phenylthio) Methyl) 6,7- dimethoxyquinazolin-4(3H)-ones as Potential Anticonvulsant Agents

Novel N3 aryl/heteroaryl substituted 2-((benzyloxy and phenylthio) methyl) 6,7-dimethoxyquinazolin-4(3H)- ones (8a-8l) were synthesized and evaluated for their anticonvulsant activity using various models of epilepsy, such as maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and intracerebroventricular AMPA (α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid)-induced seizures in mice. The rotarod test has been used to determine the acute neurotoxicity. Further, the serum enzymatic activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed along with histopathological examination of liver. Among all the derivatives, compound 8f displayed significant activity profile based on the overall magnitude of activity and minimum neurotoxicity.