Participation of the beta-hydroxyketone part for potent cytotoxicity of callystatin A, a spongean polyketide.
The participation of the beta-hydroxyketone part of callystatin A in the potent cytotoxicity was analyzed through the analogue-syntheses and the assessment of their biological potencies. The ketonic carbonyl, the 19-hydroxyl, and the three asymmetric methyl groups located in the beta-hydroxyketone part of callystatin A were revealed to contribute to the cytotoxic potency, respectively. Moreover, the alpha,beta-unsaturated delta-lactone portion was shown to serve as a conclusive functional group for the cytotoxic activity.
Murakami
N
N
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Sugimoto
M
M
Kobayashi
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007659:Ketones / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D003603:Cytotoxins; D005231:Fatty Acids, Unsaturated; D007659:Ketones; D007783:Lactones; C421091:callystatin A; C038753:leptomycin B