Synthesis and Evaluation Of Antibacterial Indole Heterocyclic Derivatives and Its Probe SAR

Abstract

Gram-negative infections are running out of drugs to cure as they are resisting almost all available drugs. The unending rise of antimicrobial resistance among Gram-negative bacteria is a serious threat to every individual of this planet. Unavailability of novel antibiotics for the treatment of Gram-negative infections exacerbates the condition, suggesting necessity of new drugs. Rapid appearance of resistance affected badly the improvement of available drugs. As a result, the LpxC (UDP-3-O-acyl-N-acetylglucosamine deacetylase), a crucial zinc-dependent metalloamidase enzyme catalyzing the first committed step of lipid A biosynthesis, has never been utilized by current drugs. Hence, LpxC has appeared as a novel and promising drug target for development of potent Gram-negative agents. newlineIn Chapter I, I survey the clinically dominant multi-drug resistance Gram-negative bacteria, the threats of antimicrobial resistance, several features of LpxC enzyme which make it a promising drug target, the history of development of LpxC inhibitors and highlight the design of indole containing heterocyclic compound, based on general structural motif of L-161,240, as novel antibacterial agent. newlineIn Chapter II, I survey the various biological activities of indole-2-carboxamides; discuss synthesis, characterization and antimicrobial evaluation of novel indole-2-carboxamides. Indole-2-carboxamides composed of cycloaliphatic amines show improved antibacterial activity than that of aromatic amines. None of the prepared compounds show considerable antifungal activity indicating potency of 5-arylindole-2-carboxamides towards bacterial strains than fungi. newlineIn Chapter III, I survey the various biological activities of 5-substitutedindole-2-carboxamides; discuss synthesis, characterization, antimicrobial evaluation and SAR study of novel 5-substitutedindole-2-carboxamides. Many compounds showed excellent antibacterial activity (i.e. 14i, 14j, 14k against K. pneumoniae, 11a, 11b, 11c, 14i, 14k against E. coli, 11a, 11c, 11g, 11h, 14i, 14k against