New substituted C-19-andrographolide analogues with potent cytotoxic activities.

Abstract

Andrographolide, the major diterpenoid lactone from Andrographis paniculata, is toxic against cancer cells. In the present study, we investigated the structure-activity relationships (SARs) of 19 andrographolide analogues which were synthesized by modification at the three hydroxyl groups. A number of the andrographolide analogues showed much higher cytotoxic activities than that of the parent compound on cancer cells including P-388, KB, COL-2, MCF-7, LU-1 and ASK cells. SAR studies of the synthetic analogues indicated that the introduction of silyl ether or triphenylmethyl ether group into C-19 of the parent compound led to increase in toxicity against the cancer cells. The 19-O-triphenylmethyl ether analogue 18 showed higher cytotoxic activity than the potent anticancer drug ellipticine, and this analogue may serve as a potential structure lead for the development of new anticancer drugs.

• Authors: Uthaiwan Sirion, Sakkasem Kasemsook, Kanoknetr Suksen, Pawinee Piyachaturawat, Apichart Suksamrarn, Rungnapha Saeeng
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 1 Pg. 49-52 (Jan 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22154665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Diterpenes
• Lactones
• andrographolide

Topics

• Andrographis (metabolism)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Chemistry, Pharmaceutical (methods)
• Diterpenes (chemistry)
• Drug Design
• Drug Screening Assays, Antitumor (methods)
• Humans
• Inhibitory Concentration 50
• Lactones (pharmacology)
• Models, Chemical
• Structure-Activity Relationship