SYNTHESIS, IN-VITRO ANTIMICROBIAL EVALUATION AND MOLECULAR DOCKING STUDIES OF SOME NOVEL ACETOPHENONES SUBSTITUTED QUINOXALINE THIOSEMICARBAZIDE DERIVATIVESAbstract
In the present research worked aims to increase the antimicrobial activity of quinoxaline thiosemicarbazide derivatives by substitution of some acetophenones and their antimicrobial evaluation against various antimicrobial strains with molecular docking studies. Lead molecule (1E, 4E)-1-(7-chloro-3-isopropylquinoxalin-2(1H)-ylidene) thiosemicarbazide was synthesized and condensed with various substituted acetophenones to synthesize derivatives. All derivatives were characterized by IR., NMR & Mass spectroscopy. The synthesized derivatives were evaluated in-vitro for antibacterial and antifungal activities against various strains using the agar dilution method. Molecular docking studies of the derivatives (Va – Vg) were performed against E. coli DNA gyrase B and Topoisomerase IV to find out essential binding sites against target protein PDB: 1AJ6 and 1S14, respectively. Among all these compounds,Vf and Vg were found to exhibit more potent activity against Gram –Ve, Gram +Ve bacterial and fungal strains at MIC 0.19 µg/ml, 0.39µg/ml, and 0.78 µg/ml, respectively. The docking studies of all the compounds exhibit potent binding energy, but the compound Vg exhibit interactive binding energy -8.1 and -7.5 kcal/mol to the active pockets of E.coli DNA gyrase B and Topoisomerase IV against target protein PDB: 1AJ6 and 1S14, respectively. The compound Vg interacting with various active sites of amino acids of DNA gyrase B like ASN 46, ILE 94, ILE 78, PRO 79, ARG 76, THR 165, ASP 73 & VAL 71, and Topoisomerase IV like ASP 1133, ASP 1070, ARG 1159, ARG 1072, THR 1161 & HIST 1051.In terms of structure-activity relationship study, it is revealed that the activity profile against bacterial and fungal strains was altered by the formation of acetophenones substituted (1E, 4E)-1-(7-chloro-3-isopro-pylquinoxalin-2(1H)-ylidene) thiosemicarbazide derivatives.