Haliclonacyclamines, tetracyclic alkylpiperidine alkaloids, as anti-dormant mycobacterial substances from a marine sponge of Haliclona sp.
A new tetracyclic alkylpiperidine alkaloid, 22-hydroxyhaliclonacyclamine B (1), together with two known alkaloids, haliclonacyclamine A (2) and B (3), were isolated from a marine sponge of Haliclona sp. as anti-dormant mycobacterial substances. The chemical structure of 22-hydroxyhaliclonacyclamine B (1) was determined on the basis of spectroscopic study. The compounds 2 and 3 showed strong anti-mycobacterial activity against Mycobacterium smegmatis and M. bovis Bacille de Calmette et Guérin (BCG) under both aerobic condition and hypoxic condition inducing dormant state with minimum inhibitory concentrations (MICs) in the ranges of 1.0-2.5 microg/ml. In addition, the anti-microbial activity of compound 3 was bactericidal against M. bovis BCG under both aerobic and hypoxic conditions. The 22-hydroxy group in 1 was found to reduce anti-mycobacterial activity, because 22-hydroxyhaliclonacyclamine B (1) exhibited weaker anti-microbial activities against Mycobacterium bacilli with MICs in the ranges of 12.5-50 microg/ml.
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Masayoshi
M
Arai
Shunsuke
S
Ishida
Andi
A
Setiawan
Motomasa
M
Kobayashi
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009161:Mycobacterium / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*
C545778:22-hydroxyhaliclonacyclamine B; D000470:Alkaloids; D000995:Antitubercular Agents; D047028:Macrocyclic Compounds; D010880:Piperidines; C114409:haliclonacyclamine A; C114410:haliclonacyclamine B