Nishanth.R, Kaushik Chanda
Department of chemistry, Vellore Institute of Technology, India.
Title: An Expeditious Green Synthetic Design to Access Low Molecular Weight Novel Hybrid Bifunctional Molecules as Anti-Microbials
Biography
Biography: Nishanth.R, Kaushik Chanda
Abstract
Antibiotic resistance is a threatening issue being faced by the world today.It is an intrinsic part of bacterial evolution whose genetic basis arise via, chromosomal mutation of bacteria or by the acquisition of resistance genes from other bacteria by horizontal gene transfer [HGT] and by production of β-lactamase. To some extent, bifunctional and hybrid antimicrobials are considered to be the successful outcome of research towards bacterial resistance.MCB-3861 is one such example of fluoroquinolone-oxazolidinone hybrid anti-microbial with a 4-hydroxy piperidinyl linker. It shows resistance against several clinically relevant gram-positive pathogens, including Vancomycin-Resistant Enterococci (VRE), E. faecalis S. pneumonia. Considering an amide in a general view resonance on nitrogen atom attains planar structure with sp2 hybridization which gives best overlap of orbitals with the adjacent carbonyl carbon atom making it less electrophilic and less reactive. Contrarily extensive literature survey on SAR of the lactam containing antimicrobials reveals that, 4-5 ring system in penicillin prevents nitrogen atom in lactam ring from attaining sp2 hybridization. In addition actual ideal bond angle (109.5°) of the sp3 hybridized carbon atom in lactam ring is constricted to 90° leading to angle strain making it susceptible to degradation by βlactamase. From our preliminary work, we found that imidazo [1,2-a]pyridine/pyrimidine/pyrazine derivatives with methyl and methoxy substitutions would be active against gram positive and gram negative bacteria. In this context we underpinned a design to synthesize hybrid antimicrobials by inception of thiazetidine/oxazetidine and thiazolidine/oxazolidine moieties to methyl or methoxy substituted imidazo/ thiazo pyridine/ pyrimidine/pyrazine derivatives which could make a way in discovery of novel hybrid antimicrobials.