Isolation of caldorazole, a thiazole-containing polyketide with selective cytotoxicity under glucose-restricted conditions
Isolation of caldorazole, a thiazole-containing polyketide with selective cytotoxicity under glucose-restricted conditions
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卡多拉唑（一种在葡萄糖限制条件下具有选择性细胞毒性的含噻唑聚酮化合物）的分离
DOI：
10.1021/acs.orglett.2c01566
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发表时间：
2022
期刊：
影响因子：
5.2
通讯作者：
Kiyotake Suenaga
中科院分区：
文献类型：
--
作者：
Osamu Ohno;Arihiro Iwasaki;Kyouhei Same;Chihiro Kudo;Erika Aida;Kazuya Sugiura;Shimpei Sumimoto;Toshiaki Teruya;Etsu Tashiro;Siro Simizu;Kenji Matsuno;Masaya Imoto;Kiyotake Suenaga
Caldorazole（1）是从海洋蓝藻Caldorasp中分离得到的。收集于日本冲绳的石垣岛。其结构经测定为含两个噻唑环和一个O-亚甲基N，N-二甲基乙酰胺的新型聚酮化合物。卡多唑（1）对高密度接种的肿瘤细胞显示出较强的细胞毒性。在HeLa和A431细胞中，仅在糖酵解阻断剂2-脱氧-D-葡萄糖（2DG）存在下观察到1诱导的细胞死亡。1DG和2DG联合处理可显著降低细胞内ATP水平。此外，1选择性地抑制线粒体呼吸链中的复合物I。因此，1通过阻断线粒体呼吸而对人肿瘤细胞产生细胞毒性。
Caldorazole (1) was isolated from the marine cyanobacteriumCaldorasp. collected on Ishigaki Island, Okinawa, Japan. Its structure was determined to be a new polyketide that contained two thiazole rings and anO-methylenolpyruvamide moiety. Caldorazole (1) showed strong cytotoxicity toward tumor cells that had been seeded at a high density. Cell death induced by1in HeLa and A431 cells was also observed only in the presence of the glycolysis blocker 2-deoxy-d-glucose (2DG). Co-treatment with1and 2DG remarkably decreased ATP levels in these cells. Furthermore,1selectively inhibited complex I in the mitochondrial respiratory chain. Thus,1was demonstrated to exert cytotoxicity toward human tumor cells by blocking mitochondrial respiration.