Vasantha Kumar

Novel benzimidazole–oxadiazole hybrid molecules as promising antimicrobial agents

In the present study, we describe the design and expeditious synthesis of novel 2-aryl-5-(3-aryl-[1,2,4]-oxadiazol-5-yl)-1-methyl-1H-benzo[d]imidazole hybrid molecules as promising antimicrobial agents. The core moiety 2-aryl-ethyl-1H-benzo[d]imidazole-5-carboxylate was efficiently synthesized by a rapid ‘one pot’ nitro reductive cyclization reaction using sodium dithionite as reagent. All the compounds were screened for their antimicrobial activities and the active compounds were screened for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain by the Microplate Alamar Blue Assay method. Compounds 8k, 8n, 8p and 8r exhibited potent anti-tubercular activity with MIC of 1.6 μg mL−1, which is two times more potent than the standard drugs pyrazinamide and ciprofloxacin and fourfold superior to streptomycin and isoniazid. Further, potent compounds were tested for their preliminary toxicity by hemolytic assay, where the compounds remain nontoxic even at higher concentration and showed good selectivity index. The investigation of cytotoxicity against normal embryonic kidney cell line HEK 293 by MTT assay showed IC50 value of more than 355 μg mL−1 for all the tested potent compounds. From the screening study, 8k, 8n, 8p and 8r emerged as strong candidates with potent antimicrobial activities and good ADME parameters. Attempts were also made to establish the structural activity relationships among the tested compounds.

Synthesis of Some Novel 1,2-Disubstituted Benzimidazole-5-carboxylates via One-Pot Method Using Sodium Dithionite and Its Effect on N-Debenzylation

Abstract A series a novel of 1,2-disubstituted benzimidazole-5-carboxylates were prepared by the one-pot nitroreductive cyclization route using sodium dithionite, and its effect on N-debenzylation has been described. Different ethyl 4-(alkyl/arylamino)-3-nitrobenzoates were reacted with various aromatic/heteroaromatic aldehydes in dimethyl sulfoxide to yield the target benzimidazoles in good yield and purity. Wide varieties of aldehydes used for the cyclization were found to be susceptible under the reaction conditions. This method afforded the products within a very short reaction time and isolation was an easy workup procedure. Debenzylation resulting in the cleavage of the N-benzyl group was observed under experimental conditions with sodium dithionite without the aid of any cocatalyst and the presence of ethanol increased the extent of debenzylation. GRAPHICAL ABSTRACT

SYNTHESIS AND BIOLOGICAL EVALUATION OF N-(SUBSTITUTED PHENYL)-2-(5H-[1,2,4]TRIAZINO[5,6-b]INDOL-3-YLSULFANYL)ACETAMIDES AS ANTIMICROBIAL, ANTIDEPRESSANT AND ANTICONVULSANT AGENTS.

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

Biological evaluation and in silico molecular docking study of a new series of thiazol-2-yl-hydrazone conglomerates

A new series of hybridized thiazol-2-yl-hydrazone derivatives having diverse substituents were designed, synthesized, and screened for their anti-inflammatory property by a carrageenan-induced paw edema method. The compounds 11a, 11b, 11c, 11d, 11e, 11g, 11m and 11p revealed significant inhibition when compared to Diclofenac sodium. Subsequently, two highly potent compounds (11d and 11e) were evaluated for their cytotoxic effect on the tumor cell line. The binding interactions of thiazol-2-yl-hydrazones with the cyclooxygenase-2 (COX-2) protein (PDB: 3LN1) displayed effective interactions with Arg-120, Tyr-385 and Tyr-355 amino acids, the main criteria of the COX-2 inhibitor. In addition, all the compounds showed moderate to good in vitro antibacterial activity. Most active benzyloxy derivatives were also tested to understand the radical scavenging efficacy by the 2,2-diphenyl-1-picrylhydrazyl method.Graphical Abstract