Participation of the conjugated diene part for potent cytotoxicity of callystatin A, a spongean polyketide.
5-epi, 10-epi, 8-Deethyl, and 10-demethyl analogues of callystatin A, a potent cytotoxic spongean polyketide, were synthesized to elucidate structure-requirement for cytotoxic potency. Inversion of the asymmetric center at C-10 in callystatin A minimally affected the activity, while lack of the 10-methyl group in callystatin A decreased cytotoxicity. In addition, the C-5 epimer and the 8-deethyl analogue of callystatin A showed weaker cytotoxicity.
Murakami
N
N
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Sugimoto
M
M
Nakajima
T
T
Kawanishi
M
M
Tsutsui
Y
Y
Kobayashi
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D002942:Circular Dichroism; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D005231:Fatty Acids, Unsaturated; C421091:callystatin A; C038753:leptomycin B