02186nas a2200241   4500008004100000022001400041245017800055210006900233260000800302300001100310490000800321520130800329653003101637653001201668653002101680653001701701100001701718700002101735700001901756700002601775700001901801856012401820       2026                        eng d  a0045-206800aElucidating the potential of novel class biphenyl-phenyl acetate, IDD-AN-A1, an inhibitor targeting Isocitrate Lyase in Mycobacterium tuberculosis: a target to lead approach0 aElucidating the potential of novel class biphenylphenyl acetate   cMAR  a1095570 v1703 a<p>
	Isocitrate lyase (ICL), a pivotal enzyme of the glyoxylate shunt pathway in Mycobacterium tuberculosis (Mtb), represents an attractive target for the development of new anti-tuberculosis (TB) therapeutics. In this study, we identified 2-methoxy-4-((nitrosooxy)methyl)phenyl 2-(2-fluoro-[1,1 `-biphenyl]-4-yl)propanoate (IDDAN-A1) as a potent inhibitor of Mtb ICL. The compound exhibited strong activity against Mtb, with a minimum inhibitory concentration of 6.25 mu g/mL, and demonstrated potent inhibition in enzyme-based assays targeting ICL. Molecular docking studies further supported Mtb ICL as the potential molecular target of this compound. Cytotoxicity and hemolytic assays revealed a favorable safety profile for the compound with selectivity index &gt;10. In combination studies, it exhibited additive and synergistic activity with the frontline drug Rifampicin and Delamanid respectively. Additionally, ex vivo assays simulating the intracellular environment of the pathogen demonstrated strong inhibitory potency. In vitro inhibition studies further confirmed the bacteriostatic nature of the compound across different concentrations. Collectively, these findings demonstrate that this molecule possesses promising anti-tuberculosis activity by targeting the ICL enzyme in Mtb.</p>
10aAnti-tuberculosis activity10aEx vivo10aIsocitrate lyase10atuberculosis1 aNegi, Anjali1 aPerveen, Summaya1 aKour, Harpreet1 aSawant, Sanghapal, D.1 aSharma, Rashmi  uhttps://library.ncl.res.in/content/elucidating-potential-novel-class-biphenyl-phenyl-acetate-idd-a1-inhibitor-targeting