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

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

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1 Citation (Scopus)

Abstract

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. 2022 American Chemical Society.

Original languageEnglish
Pages (from-to)4547-4551
Number of pages5
JournalOrganic Letters
Volume24
Issue number25
DOIs
Publication statusPublished - 2022 Jul 1

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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