Synthesis and biological evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofurans as a new class of antitubulin agents.

Abstract

Microtubules are among the most successful targets for development of compounds useful for anticancer therapy. Continuing our project to develop new small molecule antitumor agents, two new series of derivatives based on the 2-aroyl-4-phenylbenzofuran molecular skeleton were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. SAR were elucidated with various substitutions on the benzoyl moiety at the 2-position of the benzofuran ring. The most promising compound in this series, the (5-hydroxy-4-phenylbenzofuran-2-yl)(4-methoxyphenyl)methanone derivative (3d), has significant growth inhibitory activity in the submicromolar range against the Molt4, CEM and HeLa cancer cell lines and interacts with tubulin by binding to the colchicine site. Exposure to 3d led to the arrest of K562 cells in the G2-M phase of the cell cycle and to the induction of apoptosis.

• Authors: Romeo Romagnoli, Pier Giovanni Baraldi, Taradas Sarkar, Carlota Lopez Cara, Olga Cruz Lopez, Maria Dora Carrion, Delia Preti, Manlio Tolomeo, Jan Balzarini, Ernest Hamel
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 4 Issue 6 Pg. 558-64 (Nov 2008) ISSN: 1573-4064 [Print] Netherlands
• PMID: 18991740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzofurans
• Tubulin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzofurans (chemical synthesis, chemistry, pharmacology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Design
• Flow Cytometry
• G2 Phase (drug effects)
• Humans
• Magnetic Resonance Spectroscopy
• Mice
• Microtubules (drug effects)
• Tubulin (biosynthesis, drug effects)