Murakami N, Sugimoto M, Nakajima T, Kawanishi M, Tsutsui Y, Kobayashi M
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Bioorg Med Chem. 2000 Nov;8(11):2651-61. doi: 10.1016/s0968-0896(00)00199-1.
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.
合成了具有细胞毒性的海绵聚酮化合物——抑癌他汀A的5-表位、10-表位、8-去乙基和10-去甲基类似物，以阐明细胞毒性效力的结构要求。抑癌他汀A中C-10位不对称中心的构型翻转对活性影响最小，而抑癌他汀A中缺少10-甲基则会降低细胞毒性。此外，抑癌他汀A的C-5差向异构体和8-去乙基类似物显示出较弱的细胞毒性。
