Dr. Tanay Kesharwani

Antimicrobial Resistance (AMR) is the next impending health crisis knocking at our doors and the biggest challenge in fighting AMR infections is the scarcity of novel and effective antibiotics. The objective of this study is to evaluate novel class of compounds called benzothiophenes for their potential antimicrobial activity. Previous studies have indicated great promise of benzothiophene derivatives as an important biological core structure. Benzo[b]thiophene core structure is present in several FDA-approved drugs, such as raloxifene, zileuton, and sertaconazole. In this study, the novel benzothiophene derivatives were synthesized using common organic synthesis methods such as Sonogashira coupling and electrophilic cyclization reactions. Proton nuclear magnetic resonance (1H-NMR), carbon nuclear magnetic resonance (13C-NMR), gas chromatography-mass spectroscopy (GC-MS), and high-performance liquid chromatography (HPLC) were used to determine compound identity and purity. The compounds were tested against gram positive bacteria (S. aureus, M. luteus, and E. faecalis), gram-negative bacteria (E. coli, and P. aeruginosa) and fungi such as C. albicans and C. tropicalis, via a broth microdilution susceptibility assay in a 96-well plate. Briefly, varying concentrations of the compound were incubated with the cells. After incubation, the plates were read using a plate reader to determine the absorbance and minimum inhibitory concentration (MIC) values. The low MIC values for the benzo[b]thiophene derivative compounds signify a promising antimicrobial activity. Further biological studies were performed to determine the toxicity of the compounds to human cell lines. Preliminary results showed that addition of some groups increased the antibacterial activity of the benzo[b]thiophene derivatives while addition of other groups decreased the activity of the compounds. In conclusion, this project will help to identify more potent benzo[b]thiophene derivatives with broader efficacy against both bacteria and fungi. This research accomplishes crucial steps toward developing potent benzo[b]thiophenes as a possible clinical candidate as an antimicrobial drug.