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

Fingerprint

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

Cite this

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

@article{3436ec59c652421582975d4faaaac0a1,

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

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.",

keywords = "Actin, Actin-depolymerizing activity, Aplyronine A, Apoptosis, Mycalolide B",

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

year = "2013",

month = mar

day = "1",

doi = "10.1016/j.bmcl.2012.12.052",

language = "English",

volume = "23",

pages = "1467--1471",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "5",

}

TY - JOUR

T1 - Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives

AU - Ohno, Osamu

AU - Morita, Maho

AU - Kitamura, Kazuhiro

AU - Teruya, Toshiaki

AU - Yoneda, Kozo

AU - Kita, Masaki

AU - Kigoshi, Hideo

AU - Suenaga, Kiyotake

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

KW - Actin

KW - Actin-depolymerizing activity

KW - Aplyronine A

KW - Apoptosis

KW - Mycalolide B

UR - http://www.scopus.com/inward/record.url?scp=84873732831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873732831&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.12.052

DO - 10.1016/j.bmcl.2012.12.052

M3 - Article

C2 - 23357626

AN - SCOPUS:84873732831

VL - 23

SP - 1467

EP - 1471

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -

Access to Document

10.1016/j.bmcl.2012.12.052