Anti-tuberculosis constituents from the stem bark of Micromelum hirsutum

Planta Med. 2005 Mar;71(3):261-7. doi: 10.1055/s-2005-837826.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Humans
  • Macrophages / microbiology
  • Mice
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / pathogenicity
  • Phytotherapy*
  • Plant Bark
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rutaceae*

Substances

  • Antitubercular Agents
  • Plant Extracts