Planta Med 2005; 71(3): 261-267
DOI: 10.1055/s-2005-837826
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Anti-Tuberculosis Constituents from the Stem Bark of Micromelum hirsutum

Cuiying Ma1 , Ryan J. Case2 , Yuehong Wang2 , Hong-Jie Zhang1 , Ghee Teng Tan1 , Nguyen Van Hung3 , Nguyen Manh Cuong4 , Scott G. Franzblau2 , Djaja Djendoel Soejarto1 , Harry H. S. Fong1 , Guido F. Pauli1 , 2
  • 1Program for Collaborative Research in the Pharmaceutical Sciences, M/C 781, Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, the University of Illinois at Chicago, Chicago, Illinois, USA
  • 2Institute for Tuberculosis Research, M/C 964, College of Pharmacy, the University of Illinois at Chicago, Chicago, Illinois, USA
  • 3Institute of Chemistry, Vietnamese Academy of Science and Technology, Hanoi, Vietnam
  • 4Cuc Phuong National Park, Nho Quan District, Ninh Binh Province, Vietnam
Further Information

Publication History

Received: June 24, 2004

Accepted: October 14, 2004

Publication Date:
15 March 2005 (online)

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.

References

Guido F. Pauli, PhD, PharmD

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

Illinois 60612

USA

Phone: +1-312-355-1949

Fax: 1-312-3555-2693

Email: gfp@uic.edu