01775nas a2200277   4500008004100000245014700041210006900188260000800257300001200265490000800277520079400285100002201079700002601101700002001127700002401147700002201171700002301193700002001216700002101236700001701257700001901274700002401293700003001317700002201347856012801369       2019                        eng d00aSynthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis0 aSynthesis and biological evaluation of 245trisubstituted thiazol  cSEP  a315-3280 v1783 a<p>The dormant and resistant form of Mycobacterium tuberculosis presents a challenge in developing new anti-tubercular drugs. Herein, we report the synthesis and evaluation of trisubstituted thiazoles as antituberculosis agents. The SAR study has identified a requirement of hydrophobic substituent at C2, ester functionality at C4, and various groups with hydrogen bond acceptor character at C5 of thiazole scaffold. This has led to the identification of 13h and 13p as lead compounds. These compounds inhibited the dormant Mycobacterium tuberculosis H37Ra strain and M. tuberculosis H37Rv selectively. Importantly, 13h and 13p were non-toxic to CHO cells. The 13p showed activity against multidrug-resistant tuberculosis isolates. (C) 2019 Elsevier Masson SAS. All rights reserved.</p>
1 aKarale, Uttam, B.1 aKrishna, Vagolu, Siva1 aKrishna, Vamshi1 aChoudhari, Amit, S.1 aShukla, Manjulika1 aGaikwad, Vikas, R.1 aMahizhaveni, B.1 aChopra, Sidharth1 aMisra, Sunil1 aSarkar, Dhiman1 aSriram, Dharmarajan1 aDusthackeer, V., N. Azger1 aRode, Haridas, B.  uhttps://library.ncl.res.in/content/synthesis-and-biological-evaluation-245-trisubstituted-thiazoles-antituberculosis-agents01673nas a2200181   4500008004100000022001400041245006700055210006500122260000900187300001600196490000700212520109500219100002201314700002001336700002101356700002101377856009301398       2020                        eng d  a0022-262300aTeixobactin: a paving stone toward a new class of antibiotics?0 aTeixobactin a paving stone toward a new class of antibiotics  cNOV   a12171-121950 v633 a<p>Antimicrobial resistance is a serious threat to human health worldwide, prompting research efforts on a massive scale in search of novel antibiotics to fill an urgent need for a remedy. Teixobactin, a macrocyclic depsipeptide natural product, isolated from uncultured bacteria (Elef theria terrae), displayed potent activity against several Gram-positive pathogenic bacteria. The distinct pharmacological profile and interesting structural features of teixobactin with nonstandard amino acid (three Damino acids and L-allo-enduracididine) residues attracted several research groups to work on this target molecule in search of novel antibiotics with new mechanism. Herein, we present a comprehensive and critical perspective on immense possibilities offered by teixobactin in the domain of drug discovery. Efforts made by various research groups since its isolation are discussed, highlighting the molecule's considerable potential with special emphasis on replacement of amino acids. Critical analysis of synthetic efforts, SAR studies, and the way forward are provided hereunder.</p>
1 aGunjal, Vidya, B.1 aThakare, Ritesh1 aChopra, Sidharth1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/teixobactin-paving-stone-toward-new-class-antibiotics02084nas a2200289   4500008004100000022001400041245009100055210006900146260000800215300001600223490000700239520114900246100001701395700001901412700003301431700002201464700001901486700001601505700002501521700001701546700002101563700002301584700002601607700001601633700002501649856012001674       2025                        eng d  a0022-262300aMycobacteria-specific prodrug to overcome phenotypic AMR in mycobacterium tuberculosis0 aMycobacteriaspecific prodrug to overcome phenotypic AMR in mycob  cDEC  a24935-249520 v683 a<p>
	Most front-line tuberculosis (TB) drugs are ineffective against hypoxic nonreplicating Mycobacterium tuberculosis (Mtb), largely due to poor permeability, leading to reduced drug accumulation and target engagement. To overcome this phenotypic antimicrobial resistance (AMR), we developed nitroheteroaryl prodrugs for Moxifloxacin (MXF), a front-line TB drug. These prodrugs are activated by bacterial nitroreductases (NTR), which are overexpressed in hypoxic Mtb. NTR-mediated electron transfer and protonation facilitate rapid cleavage of the protective group, releasing active MXF. The lead prodrug exhibited comparable efficacy to MXF in replicating Mtb and significantly enhanced lethality in nonreplicating Mtb. Drug accumulation studies confirmed a modest but significant increase in MXF levels in nonreplicating Mtb treated with the prodrug, suggesting improved permeability. A mathematical model integrating growth and drug-killing kinetics further elucidated how permeability differences impact lethality. Together, these findings highlight enzyme-activated prodrugs as a promising strategy to address phenotypic AMR in Mtb</p>
1 aKumar, Anand1 aBirua, Shalini1 aMallojjala, Sharath, Chandra1 aMukherjee, Piyali1 aSingh, Samsher1 aKaul, Grace1 aRamachandran, Aparna1 aAkhir, Abdul1 aChopra, Sidharth1 aGadgil, Chetan, J.1 aHirschi, Jennifer, S.1 aSingh, Amit1 aChakrapani, Harinath  uhttps://library.ncl.res.in/content/mycobacteria-specific-prodrug-overcome-phenotypic-amr-mycobacterium-tuberculosis