title: Design, synthesis and inhibition activity of a novel cyclic enediyne amino acid conjugates against MPtpA.
abstract: In course of studies towards the discovery of selective inhibitors of MPtpA, a novel cyclic endiyne malonamic acid has been designed and synthesized. The synthesis involves a crucial intramolecular Knoevenagel reaction. The compound displayed a reversible non-competitive inhibition against MPtpA with inhibition constant K(i) of 22.5 μM. The enediyne acts as a recognition framework in inducing the inhibition and not as a reactive functional moiety. This was confirmed by comparing the inhibiting activity with that of the corresponding saturated cyclic non-enediyne analogue.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur, India.
authors.forename: Koushik
authors.initials: K
authors.lastname: Chandra
authors.forename: Debajyoti
authors.initials: D
authors.lastname: Dutta
authors.forename: Analava
authors.initials: A
authors.lastname: Mitra
authors.forename: Amit K
authors.initials: AK
authors.lastname: Das
authors.forename: Amit
authors.initials: A
authors.lastname: Basak
mesh_terms: D000598:Amino Acids, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003500:Cyclization; D015195:Drug Design; D053281:Enediynes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000598:Amino Acids, Cyclic; D001426:Bacterial Proteins; D053281:Enediynes; D004791:Enzyme Inhibitors; D008314:Malonates; C414465:MptpA protein, Mycobacterium tuberculosis; C013098:malonamic acid; D017027:Protein Tyrosine Phosphatases