Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives

Osamu Ohno; Maho Morita; Kazuhiro Kitamura; Toshiaki Teruya; Kozo Yoneda; Masaki Kita; Hideo Kigoshi; Kiyotake Suenaga

doi:10.1016/j.bmcl.2012.12.052

Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives

Osamu Ohno, Maho Morita, Kazuhiro Kitamura, Toshiaki Teruya, Kozo Yoneda, Masaki Kita, Hideo Kigoshi, Kiyotake Suenaga

Department of Chemistry

Research output: Contribution to journal › Article

16 Citations (Scopus)

Abstract

Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S₃ cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.

Original language	English
Pages (from-to)	1467-1471
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2012.12.052
Publication status	Published - 2013 Mar 1

Keywords

Actin
Actin-depolymerizing activity
Aplyronine A
Apoptosis
Mycalolide B

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Ohno, O., Morita, M., Kitamura, K., Teruya, T., Yoneda, K., Kita, M., Kigoshi, H., & Suenaga, K. (2013). Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives. Bioorganic and Medicinal Chemistry Letters, 23(5), 1467-1471. https://doi.org/10.1016/j.bmcl.2012.12.052

Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives. / Ohno, Osamu; Morita, Maho; Kitamura, Kazuhiro; Teruya, Toshiaki; Yoneda, Kozo; Kita, Masaki; Kigoshi, Hideo; Suenaga, Kiyotake.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 5, 01.03.2013, p. 1467-1471.

Research output: Contribution to journal › Article

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abstract = "Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S3 cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.",

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