Heteroaromatic analogs of the resveratrol analog DMU-212 as potent anti-cancer agents.

Abstract

Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13 and 14, respectively) and showed potent growth inhibition in 85% of the cancer cell lines examined, with GI50 values <1 μM. Interestingly, trans-3,4- and trans-3,5-dimethoxystyryl DMU-212 analogs 9, 10, 12 and 15 exhibited significantly less growth inhibition than their 3,4,5-trimethoxystyryl counterparts, suggesting that the trans-3,4,5-trimethoxystyryl moiety is an essential structural element for the potent anti-cancer activity of these heterocyclic DMU-212 analogs. Molecular modeling studies showed that the four most active compounds (8, 11, 13 and 14) all bind to the colchicine binding site on tubulin, and that their binding modes are similar to that of DMU-212.

• Authors: Narsimha Reddy Penthala, Shraddha Thakkar, Peter A Crooks
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 14 Pg. 2763-7 (Jul 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26022840 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• 3,4,5,4'-tetramethoxystilbene
• Antineoplastic Agents
• Benzofurans
• Benzothiazoles
• Stilbenes
• Thiophenes
• Tubulin
• benzothiophene
• benzothiazole
• benzofuran
• Resveratrol
• Colchicine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzofurans (chemistry)
• Benzothiazoles (chemistry)
• Binding Sites
• Cell Line, Tumor
• Cell Survival (drug effects)
• Colchicine (chemistry, metabolism)
• Drug Screening Assays, Antitumor
• Humans
• Molecular Docking Simulation
• Protein Structure, Tertiary
• Resveratrol
• Stilbenes (chemical synthesis, chemistry, pharmacology)
• Thiophenes (chemistry)
• Tubulin (chemistry, metabolism)