Synthesis and evaluation of triazole congeners of nitro-benzothiazinones potentially active against drug resistant Mycobacterium tuberculosis demonstrating bactericidal efficacy

Abstract

With growing concerns of target residue mutation hovering over established anti-TB pharmacophores, it is imperative to have reserve chemotypes at our disposal to curb unrestrained spread of tuberculosis. In this...

Bioevaluation of quinoline‐4‐carbonyl derivatives of piperazinyl‐benzothiazinones as promising antimycobacterial agents

“…Synthesis of key intermediates 5a–e was carried out by employing a previously reported modified literature procedure. [ 40,53 ] Briefly, nitration of appropriate 2‐chlorobenzoic acid 1a–e with a nitrating mixture of concentrated nitric acid and sulfuric acid led to nitro‐substituted benzoic acid 2a–e . The formed benzoic acid product was activated to acyl chloride derivative by refluxing with thionyl chloride in chloroform before being treated with aqueous ammonia under cooling conditions to yield corresponding benzamide derivative 3a–e .…”

“…Although essential for better penetration and potency, the aliphatic side chain contributes to the low aqueous solubility of BTZs that subsequently leads to poor bioavailability. To ameliorate these limitations, recently varied C6 substituted analogs of BTZs with C2 side chain bearing five‐membered heterocyclics like oxadiazole and triazole linked through N ‐methyl amino, [ 39 ] amino/mercapto linker [ 40 ] has shown great promise. The factors like low solubility, and predisposition to target residue mutation leading to drug resistance, limits late‐stage clinical development of BTZ's.…”

Synthesis, in-silico based virtual screening,anti-cancer potential of novel1,2,3-triazole-thiadiazole hybrid derivatives as Aurora kinase A (ARK-A) and Extracellular regulated kinase 2 (ERK2) dual inhibitors

“…Triazoles ve-membered nitrogen heterocycles having three nitrogen and two carbon atoms in a ring.Triazoles are found to be effective bioisosteres of amides in bioactive molecules with diverse and important biological properties. [4][5][6][7] 1,2,3-Triazole systems the ability of hydrogen bond formation, dipoledipole and π stacking interactions, stable to reduction and oxidation. 8 1,2,3-triazoles are present in many of the drugs like theTazobactum,Carboxyamidotriazole and Ru namide etc.The triazoles arereported to have the anticancer 9,10 , antitubercular 11 , antifungal 12,13 antibacterial 14,15 , antiviral 16,17 and antiobesity 18,19 and anti-diabetic 20 properties.…”