Neo-tanshinlactone inspired synthesis, in vitro evaluation of novel substituted benzocoumarin derivatives as potent anti-breast cancer agents.

Abstract

A small library of novel benzocoumarin derivatives based on naturally occurring neo-tanshinlactone scaffold was constructed and their antiproliferative activities against breast cancer cells MCF-7 and MDA-MB-231 were evaluated. A number of derivatives showed good anti-breast cancer activity, in some cases higher to that of the reference compound tamoxifen. In particular, benzocoumarins Bc-5, Bc-8 and Bc-9 strongly inhibited the proliferation of MCF-7 cancer cell line with the IC(50) values of 3.8, 7.9 and 6.5 μM, respectively. The compounds were capable of inducing nuclear fragmentation, cell cycle arrest and caspase dependent apoptosis in MCF-7 cell lines. In addition, these derivatives were devoid of cytotoxic effect against normal osteoblast cells. These synthetic benzocoumarins hold promises for developing safer alternative to the existing anti-breast cancer agents.

• Authors: Koneni V Sashidhara, Jammikuntla N Rosaiah, Manoj Kumar, Rishi Kumar Gara, Lakshma Vadithe Nayak, Kamini Srivastava, Hemant Kumar Bid, Rituraj Konwar
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 23 Pg. 7127-31 (Dec 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20951035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Coumarins
• Furans
• Pyrones
• Small Molecule Libraries
• neotanshinlactone

Topics

• Antineoplastic Agents (chemical synthesis)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Coumarins (chemistry, pharmacology)
• Female
• Furans (chemistry)
• Humans
• Pyrones (chemistry)
• Small Molecule Libraries