Identification of dialkyl diacetylene diols with potent cancer chemopreventive activity.

Abstract

An increasing importance of chemoprevention for controlling cancer risks prompted the discovery of new active cancer chemopreventive agents. In this study, we designed and synthesized substituted hexa-2,4-diyne-1,6-diols, more structurally simplified, tunable, and easily preparable than natural gymnasterkoreaynes, and evaluated their cancer chemopreventive activities by measuring concentration of doubling quinone reductase activity (CD), cell viability, and chemopreventive index (CI). Most of the diols exhibited good CD activity and low cytotoxicity. In particular, tetradeca-5,7-diyne-4,9-diol and 2-methyltetradeca-5,7-diyne-4,9-diol showed the best cancer chemopreventive activity, approximately equipotent to that of sulforaphane. And, by synthesizing optically active stereoisomers of selected active compounds, the effect of stereochemistry was also studied. Eventually, we produced a chemopreventive compound for in vivo study.

• Authors: Chang-Yong Lee, Ji Ho Yun, Kyungsu Kang, Chu-Won Nho, Dongyun Shin
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 18 Pg. 4020-3 (Sep 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26253633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Ltd.

Chemical References

• Anticarcinogenic Agents
• NAD(P)H Dehydrogenase (Quinone)
• Acetylene

Topics

• Acetylene (chemical synthesis, chemistry, pharmacology)
• Anticarcinogenic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Design
• Hep G2 Cells
• Humans
• Molecular Structure
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Neoplasms (prevention & control)
• Structure-Activity Relationship