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 S(3) 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.

• Authors: Osamu Ohno, Maho Morita, Kazuhiro Kitamura, Toshiaki Teruya, Kozo Yoneda, Masaki Kita, Hideo Kigoshi, Kiyotake Suenaga
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 5 Pg. 1467-71 (Mar 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23357626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Actins
• Antineoplastic Agents
• Macrolides
• Marine Toxins
• Oxazoles
• mycalolide B
• aplyronine A

Topics

• Actins (antagonists & inhibitors, chemistry, metabolism)
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Drug Screening Assays, Antitumor
• HL-60 Cells
• HeLa Cells
• Humans
• Macrolides (chemistry, pharmacology)
• Marine Toxins
• Molecular Structure
• Oxazoles (chemistry, pharmacology)