Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines.

Abstract

A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their topoisomerase inhibitory activity as well as their cytotoxicity against several human cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containing furyl or thienyl moiety at 4-position of central pyridine exhibited strong topoisomerase I and II inhibitory activity compared to positive control, camptothecin and etoposide, respectively, in low micromolar range. Structure-activity relationship study revealed that indenopyridine compounds with hydroxyl group at 2-phenyl ring in combination with furyl or thienyl moiety at 4-position are important for topoisomerase inhibition. Compounds (22-25) which contain hydroxyl group at meta position of the 2-phenyl ring at 2-position and furanyl or thienyl substitution at 4-position of indenopyridine, showed concrete correlations between topo I and II inhibitory activity, and cytotoxicity against evaluated human cancer cell lines.

• Authors: Tara Man Kadayat, Chanju Song, Somin Shin, Til Bahadur Thapa Magar, Ganesh Bist, Aarajana Shrestha, Pritam Thapa, Younghwa Na, Youngjoo Kwon, Eung-Seok Lee
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 23 Issue 13 Pg. 3499-512 (Jul 01 2015) ISSN: 1464-3391 [Electronic] England
• PMID: 26022080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyridines
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors
• DNA Topoisomerases, Type I
• DNA Topoisomerases, Type II

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Binding Sites
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• DNA Topoisomerases, Type I (chemistry, metabolism)
• DNA Topoisomerases, Type II (chemistry, metabolism)
• Drug Screening Assays, Antitumor
• Humans
• Hydroxylation
• Inhibitory Concentration 50
• Molecular Structure
• Protein Binding
• Pyridines (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Topoisomerase I Inhibitors (chemical synthesis, pharmacology)
• Topoisomerase II Inhibitors (chemical synthesis, pharmacology)