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 1.0-5.0microg/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.
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Authors | Masayoshi Arai, Mari Sobou, Catherine Vilchéze, Anthony Baughn, Hiroyuki Hashizume, Patamaporn Pruksakorn, Shunsuke Ishida, Makoto Matsumoto, William R Jacobs Jr, Motomasa Kobayashi |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 16
Issue 14
Pg. 6732-6
(Jul 15 2008)
ISSN: 1464-3391 [Electronic] England |
PMID | 18556206
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Alkaloids
- Anti-Bacterial Agents
- Antitubercular Agents
- Biological Products
- Bridged Bicyclo Compounds
- Piperidines
- halicyclamine A
- IMP Dehydrogenase
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Topics |
- Alkaloids
- Animals
- Anti-Bacterial Agents
- Antitubercular Agents
(pharmacology)
- Biological Products
- Bridged Bicyclo Compounds
(pharmacology)
- IMP Dehydrogenase
(antagonists & inhibitors)
- Microbial Sensitivity Tests
- Mycobacterium
(drug effects)
- Mycobacterium bovis
(drug effects)
- Mycobacterium smegmatis
(drug effects)
- Mycobacterium tuberculosis
(drug effects)
- Piperidines
(pharmacology)
- Porifera
- Species Specificity
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