title: Hybrid triazoles: Design and synthesis as potential dual inhibitor of growth and efflux inhibition in tuberculosis.
abstract: Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (EI) have been tested with encouraging results as an adjuvant therapy for treatment of tuberculosis (TB). Although, EI have emerged as innovative approach of treatment for multi drug resistant (MDR) & extensively drug resistant tuberculosis (XDR-TB), toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known EI and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known EI. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of TB initially against Mycobacterium smegmatis mc(2)155. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 144, 145, 154 and 163 were then tested for their GEI action against Mycobacterium tuberculosis (Mtb). Synthesized compounds were also tested for their synergistic action with first line and second line anti-TB drugs and ethidium bromide (EtBr). We arrived at compound 135 as most potent dual inhibitor of tuberculosis.
authors.affiliation: Department of Chemistry, Vinayakrao Patil Mahavidyalaya, Vaijapur, 423701 Dist Aurangabad, Maharashtra, India.
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Dixit
authors.affiliation: Department of Microbiology, Dr. Babasaheb Ambedkar Marathwada University, Sub-Center, Osmanabad, 413501, Dist. Osmanabad, Maharashtra, India.
authors.forename: Prashant P
authors.initials: PP
authors.lastname: Dixit
authors.affiliation: Department of Chemistry, Vinayakrao Patil Mahavidyalaya, Vaijapur, 423701 Dist Aurangabad, Maharashtra, India. Electronic address: snthore@rediffmail.com.
authors.forename: Shivajirao N
authors.initials: SN
authors.lastname: Thore
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002478:Cells, Cultured; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D014230:Triazoles
keywords: Dual inhibition; PDST145; Resistance; Triazole; Tuberculosis