Anti-Tuberculosis Constituents from the Stem Bark of Micromelum hirsutum

Cuiying Ma, Ryan J. Case, Yuehong Wang, Hong Jie Zhang, Ghee Teng Tan, Nguyen Van Hung, Nguyen Manh Cuong, Scott G. Franzblau, Djaja Djendoel Soejarto, Harry H.S. Fong, Guido F. Pauli*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

86 Citations (Scopus)

Abstract

Anti-TB bioassay-directed fractionation led to the isolation of six carbazole alkaloids, as well as the γ-lactone derivative of oleic acid, from the CH2Cl2 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 H37Rv (MIC: 1.5 μg/mL), a selectivity index (SI) of 63, and exhibited activity against the Erdman strain of M. tuberculosis in a J774 mouse macrophage model (EC90: 5.6 μg/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 μg/mL, while compounds 4 and 5 were considered inactive (MIC > 128 μg/mL). Structure elucidation and identification were based on spectroscopic analysis, including MS, 1D/2D NMR, and a full 1H spin system analysis of 1.

Original languageEnglish
Pages (from-to)261-267
Number of pages7
JournalPlanta Medica
Volume71
Issue number3
DOIs
Publication statusPublished - Mar 2005

Scopus Subject Areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

User-Defined Keywords

  • (-)-Z-9-octadecene-4-olide
  • Anti-TB activity
  • Carbazole alkaloids
  • Micromeline
  • Micromelum hirsutum
  • Micromolide
  • Rutaceae

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