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

doi:10.1021/acs.orglett.2c01566

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

Research output: Contribution to journal › Article › peer-review

4 Citations (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 language	English
Pages (from-to)	4547-4551
Number of pages	5
Journal	Organic Letters
Volume	24
Issue number	25
DOIs	https://doi.org/10.1021/acs.orglett.2c01566
Publication status	Published - 2022 Jul 1

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.2c01566

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

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.",

author = "Osamu Ohno and Arihiro Iwasaki and Kyouhei Same and Chihiro Kudo and Erika Aida and Kazuya Sugiura and Shimpei Sumimoto and Toshiaki Teruya and Etsu Tashiro and Siro Simizu and Kenji Matsuno and Masaya Imoto and Kiyotake Suenaga",

note = "Funding Information: The authors thank Prof. Hideaki Kakeya (Kyoto University, Kyoto, Japan) and Prof. Shoichiro Suda (University of the Ryukyus) for their contributions to our studies. This work was supported by Grants-in-Aid for Scientific Research (21K05295 and 24310160) and in part by a grant for the Strategic Research Foundation Grant-aided Project for Private Universities (S1411005) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank the Shorai Foundation for Science and Technology for their financial support. Publisher Copyright: {\textcopyright} 2022 American Chemical Society. All rights reserved.",

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doi = "10.1021/acs.orglett.2c01566",

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T1 - Isolation of Caldorazole, a Thiazole-Containing Polyketide with Selective Cytotoxicity under Glucose-Restricted Conditions

AU - Ohno, Osamu

AU - Iwasaki, Arihiro

AU - Same, Kyouhei

AU - Kudo, Chihiro

AU - Aida, Erika

AU - Sugiura, Kazuya

AU - Sumimoto, Shimpei

AU - Teruya, Toshiaki

AU - Tashiro, Etsu

AU - Simizu, Siro

AU - Matsuno, Kenji

AU - Imoto, Masaya

AU - Suenaga, Kiyotake

N1 - Funding Information: The authors thank Prof. Hideaki Kakeya (Kyoto University, Kyoto, Japan) and Prof. Shoichiro Suda (University of the Ryukyus) for their contributions to our studies. This work was supported by Grants-in-Aid for Scientific Research (21K05295 and 24310160) and in part by a grant for the Strategic Research Foundation Grant-aided Project for Private Universities (S1411005) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank the Shorai Foundation for Science and Technology for their financial support. Publisher Copyright: © 2022 American Chemical Society. All rights reserved.

PY - 2022/7/1

Y1 - 2022/7/1

N2 - 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.

AB - 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.

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

Abstract

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