title: Anti-tuberculosis constituents from the stem bark of Micromelum hirsutum.
abstract: Anti-TB bioassay-directed fractionation led to the isolation of six carbazole alkaloids, as well as the gamma-lactone derivative of oleic acid, from the CH (2)Cl (2) extract of the stem bark of Micromelum hirsutum. The carbazoles include the new micromeline ( 2) and five known alkaloids: lansine ( 3), 3-methylcarbazole ( 4), methyl carbazole-3-carboxylate ( 5), 3-formylcarbazole ( 6), and 3-formyl-6-methoxycarbazole ( 7). Compound 1 was identified as the lactone derivative of oleic acid, (-)- Z-9-octadecene-4-olide, for which the trivial name micromolide ( 1) is suggested. It showed potent in vitro anti-TB activity against H37R v (MIC: 1.5 microg/mL), a selectivity index (SI) of 63, and exhibited activity against the Erdman strain of M. tuberculosis in a J774 mouse macrophage model (EC (90) : 5.6 microg/mL). Thus, 1 appears worthy of further evaluation as a potential new anti-TB agent. Isolates 2, 3, 6 and 7 had anti-TB MIC values between 14.3 and 42.3 microg/mL, while compounds 4 and 5 were considered inactive (MIC > 128 microg/mL). Structure elucidation and identification were based on spectroscopic analysis, including MS, 1D/2D NMR, and a full (1)H spin system analysis of 1.
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences, M/C 781, Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, the University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, USA.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Ma
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Case
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Ghee Teng
authors.initials: GT
authors.lastname: Tan
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Hung
authors.forename: Nguyen Manh
authors.initials: NM
authors.lastname: Cuong
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Djaja Djendoel
authors.initials: DD
authors.lastname: Soejarto
authors.forename: Harry H
authors.initials: HH
authors.lastname: Fong
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D027821:Rutaceae
chemical_list: D000995:Antitubercular Agents; D010936:Plant Extracts