Halicyclamine A, a marine spongean alkaloid as a lead for anti-tuberculosis agent.
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.
Arai
Masayoshi
M
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Sobou
Mari
M
Vilchéze
Catherine
C
Baughn
Anthony
A
Hashizume
Hiroyuki
H
Pruksakorn
Patamaporn
P
Ishida
Shunsuke
S
Matsumoto
Makoto
M
Jacobs
William R
WR
Kobayashi
Motomasa
M
D000470:Alkaloids; D000818:Animals; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents / Q000494:pharmacology*; D001688:Biological Products; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009163:Mycobacterium bovis / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011161:Porifera; D013045:Species Specificity
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D010880:Piperidines; C482962:halicyclamine A; D007168:IMP Dehydrogenase