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

doi:10.1016/j.bmc.2008.05.061

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

Microbiology

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

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 language	English (US)
Pages (from-to)	6732-6736
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2008.05.061
State	Published - Jul 15 2008

Bibliographical note

Funding Information:
The authors are grateful to Dr. Nicole J. de Voogd, National Museum of Natural History, The Netherlands for identification of the sponge. The authors also thank to Dr. Takefumi Doi, Osaka University, for cooperation of preparing transformants in electroporation step. A.D.B. is supported by a grant from the Helen Hay Whitney Foundation. This study was financially supported by grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Keywords

Anti-Mycobacterium tuberculosis
Dormant
Halicyclamine
Hypoxia
Marine sponge

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2008.05.061

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

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.",

keywords = "Anti-Mycobacterium tuberculosis, Dormant, Halicyclamine, Hypoxia, Marine sponge",

author = "Masayoshi Arai and Mari Sobou and Catherine Vilch{\'e}ze and Anthony Baughn and Hiroyuki Hashizume and Patamaporn Pruksakorn and Shunsuke Ishida and Makoto Matsumoto and Jacobs, {William R.} and Motomasa Kobayashi",

note = "Funding Information: The authors are grateful to Dr. Nicole J. de Voogd, National Museum of Natural History, The Netherlands for identification of the sponge. The authors also thank to Dr. Takefumi Doi, Osaka University, for cooperation of preparing transformants in electroporation step. A.D.B. is supported by a grant from the Helen Hay Whitney Foundation. This study was financially supported by grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.",

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T1 - Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent

AU - Arai, Masayoshi

AU - Sobou, Mari

AU - Vilchéze, Catherine

AU - Baughn, Anthony

AU - Hashizume, Hiroyuki

AU - Pruksakorn, Patamaporn

AU - Ishida, Shunsuke

AU - Matsumoto, Makoto

AU - Jacobs, William R.

AU - Kobayashi, Motomasa

N1 - Funding Information: The authors are grateful to Dr. Nicole J. de Voogd, National Museum of Natural History, The Netherlands for identification of the sponge. The authors also thank to Dr. Takefumi Doi, Osaka University, for cooperation of preparing transformants in electroporation step. A.D.B. is supported by a grant from the Helen Hay Whitney Foundation. This study was financially supported by grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - 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.

AB - 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.

KW - Anti-Mycobacterium tuberculosis

KW - Dormant

KW - Halicyclamine

KW - Hypoxia

KW - Marine sponge

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SN - 0968-0896

VL - 16

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EP - 6736

JO - Bioorganic and Medicinal Chemistry

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IS - 14

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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