Isolation of Caldorazole, a Thiazole-Containing Polyketide with Selective Cytotoxicity under Glucose-Restricted Conditions

Caldorazole (1) was isolated from the marine cyanobacterium Caldora sp. collected on Ishigaki Island, Okinawa, Japan. Its structure was determined to be a new polyketide that contained two thiazole rings and an O-methylenolpyruvamide moiety. Caldorazole (1) showed strong cytotoxicity toward tumor ce...

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Bibliographic Details
Published in:Organic letters 2022-07, Vol.24 (25), p.4547-4551
Main Authors: Ohno, Osamu, Iwasaki, Arihiro, Same, Kyouhei, Kudo, Chihiro, Aida, Erika, Sugiura, Kazuya, Sumimoto, Shimpei, Teruya, Toshiaki, Tashiro, Etsu, Simizu, Siro, Matsuno, Kenji, Imoto, Masaya, Suenaga, Kiyotake
Format: Article
Language:English
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Summary:Caldorazole (1) was isolated from the marine cyanobacterium Caldora sp. collected on Ishigaki Island, Okinawa, Japan. Its structure was determined to be a new polyketide that contained two thiazole rings and an O-methylenolpyruvamide moiety. Caldorazole (1) showed strong cytotoxicity toward tumor cells that had been seeded at a high density. Cell death induced by 1 in HeLa and A431 cells was also observed only in the presence of the glycolysis blocker 2-deoxy-d-glucose (2DG). Co-treatment with 1 and 2DG remarkably decreased ATP levels in these cells. Furthermore, 1 selectively inhibited complex I in the mitochondrial respiratory chain. Thus, 1 was demonstrated to exert cytotoxicity toward human tumor cells by blocking mitochondrial respiration.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.2c01566