Please use this identifier to cite or link to this item: https://idr.l2.nitk.ac.in/jspui/handle/123456789/13347
Full metadata record
DC FieldValueLanguage
dc.contributor.authorReddyrajula, R.-
dc.contributor.authorUdayakumar, D.-
dc.date.accessioned2020-03-31T08:45:39Z-
dc.date.available2020-03-31T08:45:39Z-
dc.date.issued2020-
dc.identifier.citationBioorganic and Medicinal Chemistry Letters, 2020, Vol.30, 2, pp.-en_US
dc.identifier.urihttps://idr.nitk.ac.in/jspui/handle/123456789/13347-
dc.description.abstractTuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyrazinamide structure using bioisosterism and rational approaches by incorporating the 1,2,3-triazole moiety. Three sets of pyrazine-1,2,3-triazoles (3a-o, 5a-o and 9a-l) are designed, synthesized and evaluated for their in vitro inhibitory potency against mycobacterium tuberculosis H37Rv. The pyrazine-1,2,3-triazoles synthesized through the bioisosteric modification displayed improved activity as compared to rationally modified pyrazine-1,2,3-triazoles. Among 42 title compounds, seven derivatives demonstrated significant anti-tubercular activity with the MIC of 1.56 ?g/mL, which are two-fold more potent than the parent compound pyrazinamide. Further, the synthesized pyrazinamide analogs demonstrated moderate inhibition activity against several bacterial strains and possessed an acceptable in vitro cytotoxicity profile as well. Additionally, the activity profile of pyrazine-1,2,3-triazoles was validated by performing the molecular docking studies against the Inh A enzyme. Furthermore, in silico ADME prediction revealed good oral bioavailability for the potent molecules. 2019 Elsevier Ltden_US
dc.titleThe bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazolesen_US
dc.typeArticleen_US
Appears in Collections:1. Journal Articles

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.