title: Potential inhibitors for isocitrate lyase of Mycobacterium tuberculosis and non-M. tuberculosis: a summary.
abstract: Isocitrate lyase (ICL) is the first enzyme involved in glyoxylate cycle. Many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (TCA cycle), especially Mycobacterium tuberculosis (MTB). In fact, ICL is a potential drug target for MTB in dormancy. With the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and HIV-coinfection, the pace of drug discovery has to be increased. There are many approaches to discovering potential inhibitor for MTB ICL and we hereby review the updated list of them. The potential inhibitors can be either a natural compound or synthetic compound. Moreover, these compounds are not necessary to be discovered only from MTB ICL, as it can also be discovered by a non-MTB ICL. Our review is categorized into four sections, namely, (a) MTB ICL with natural compounds; (b) MTB ICL with synthetic compounds; (c) non-MTB ICL with natural compounds; and (d) non-MTB ICL with synthetic compounds. Each of the approaches is capable of overcoming different challenges of inhibitor discovery. We hope that this paper will benefit the discovery of better inhibitor for ICL.
authors: Institute For Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
authors: Yie-Vern
authors: YV
authors: Lee
authors: Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia ; Natural Product and Drug Discovery Centre, Malaysian Institutes of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Block 5-A, Halaman Bukit Gambir, 11700 Penang, Malaysia.
authors: Habibah A
authors: HA
authors: Wahab
authors: Institute For Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia ; ADAPT Research Cluster, Centre for Research Initiatives, Clinical & Health Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors: Yee Siew
authors: 0000-0001-5067-2073
authors: YS
authors: Choong
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002952:Citric Acid Cycle; D004791:Enzyme Inhibitors; D007522:Isocitrate Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009170:Nontuberculous Mycobacteria / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007522:Isocitrate Lyase
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