Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent

Masayoshi Arai, Mari Sobou, Catherine Vilchéze, Anthony Baughn, Hiroyuki Hashizume, Patamaporn Pruksakorn, Shunsuke Ishida, Makoto Matsumoto, William R. Jacobs, Motomasa Kobayashi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

In the course of our search for anti-microbial agents against dormant Mycobacterium tuberculosis, halicyclamine A was re-discovered as a lead for anti-tuberculosis agent from a marine sponge of Haliclona sp. on the guidance of the constructed bioassay. Halicyclamine A showed growth inhibition against Mycobacterium smegmatis, Mycobacterium bovis BCG, and M. tuberculosis H37Ra with MICs in the range of 1.0-5.0 μg/ml under both aerobic condition and hypoxic condition inducing dormant state. The growth-inhibitory activity of halicyclamine A was bactericidal, and halicyclamine A did not exhibit cross-resistance with the currently used anti-tuberculosis drugs of isoniazid, ethambutol, rifampicin, and streptomycin. Halicyclamine A has been isolated originally as one of the active constituents inhibiting inosine 5′-monophosphate dehydrogenase (IMPDH). Then, in order to elucidate action-mechanism of halicyclamine A, we prepared IMPDH over-expressing strains of M. smegmatis. However, IMPDH was not target for halicyclamine A, because halicyclamine A showed same MIC value against the wild-type M. smegmatis and IMPDH over-expressing strains.

Original languageEnglish (US)
Pages (from-to)6732-6736
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number14
DOIs
StatePublished - Jul 15 2008

Fingerprint

Alkaloids
Tuberculosis
IMP Dehydrogenase
Mycobacterium smegmatis
Mycobacterium bovis
Mycobacterium tuberculosis
Haliclona
Ethambutol
Lead
halicyclamine A
Bioassay
Isoniazid
Porifera
Streptomycin
Rifampin
Growth
Anti-Infective Agents
Biological Assay
Pharmaceutical Preparations

Keywords

  • Anti-Mycobacterium tuberculosis
  • Dormant
  • Halicyclamine
  • Hypoxia
  • Marine sponge

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent. / Arai, Masayoshi; Sobou, Mari; Vilchéze, Catherine; Baughn, Anthony; Hashizume, Hiroyuki; Pruksakorn, Patamaporn; Ishida, Shunsuke; Matsumoto, Makoto; Jacobs, William R.; Kobayashi, Motomasa.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 14, 15.07.2008, p. 6732-6736.

Research output: Contribution to journalArticle

Arai, M, Sobou, M, Vilchéze, C, Baughn, A, Hashizume, H, Pruksakorn, P, Ishida, S, Matsumoto, M, Jacobs, WR & Kobayashi, M 2008, 'Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent', Bioorganic and Medicinal Chemistry, vol. 16, no. 14, pp. 6732-6736. https://doi.org/10.1016/j.bmc.2008.05.061
Arai, Masayoshi ; Sobou, Mari ; Vilchéze, Catherine ; Baughn, Anthony ; Hashizume, Hiroyuki ; Pruksakorn, Patamaporn ; Ishida, Shunsuke ; Matsumoto, Makoto ; Jacobs, William R. ; Kobayashi, Motomasa. / Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 14. pp. 6732-6736.
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