title: Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study.
abstract: A series of novel pyrazole linked triazolo-pyrimidine hybrids were synthesized and evaluated for their anti-tuberculosis activity against M.tb H37Rv strain. Some of the screened entities rendered promising anti-tb activity (MIC: 0.39μg/mL) and were found non toxic against Vero cells (IC50: ⩾20μg/mL). Further, the docking study against wild type InhA enzyme of Mycobacterium tuberculosis using Glide reproduced the most active inhibitors (J21 and J27) with lowest binding energies and highest Glide XP scores demonstrating efficient binding to the active pocket. Additionally, the enzyme inhibition assay and ADME prediction of the active proved to be an attest to the possibility of developing compound J27 as a potent anti-tubercular lead.
authors.affiliation: Chemistry Department, V. P. & R. P. T. P. Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India. Electronic address: jaiminbhatt1488@gmail.com.
authors.forename: Jaimin D
authors.initials: JD
authors.lastname: Bhatt
authors.affiliation: Department of Biochemistry, Shree Alpesh N. Patel P. G. Institute, Affiliated to Sardar Patel University, Anand 388001, Gujarat, India.
authors.forename: Chaitanya J
authors.initials: CJ
authors.lastname: Chudasama
authors.affiliation: Chemistry Department, V. P. & R. P. T. P. Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India. Electronic address: drkdpatel64@yahoo.co.in.
authors.forename: Kanuprasad D
authors.initials: KD
authors.lastname: Patel
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002522:Chlorocebus aethiops; D006801:Humans; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D014230:Triazoles; C031280:pyrazole; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium
keywords: ADME; Diaryl pyrazole aldehydes; Enzyme inhibition assay; Glide; Triazolopyrimidine