Synthesis of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives and evaluation of their topoisomerase I and II inhibitory activity, cytotoxicity, and structure–activity relationship

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 6; pp. 2245 - 2254
• Main Authors: Thapa, Pritam, Karki, Radha, Choi, Hoyoung, Choi, Jae Hun, Yun, Minho, Jeong, Byeong-Seon, Jung, Mi-Ja, Nam, Jung Min, Na, Younghwa, Cho, Won-Jea, Kwon, Youngjoo, Lee, Eung-Seok
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-03-2010
• Subjects: 2-(Thienyl-2-yl)-4-furyl-6-aryl pyridine; 2-(Thienyl-3-yl)-4-furyl-6-aryl pyridine; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Proliferation - drug effects; Cytotoxicity; DNA Topoisomerases, Type I - chemistry; DNA Topoisomerases, Type I - metabolism; DNA Topoisomerases, Type II - chemistry; DNA Topoisomerases, Type II - metabolism; Drug Design; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Molecular Structure; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Stereoisomerism; Structure-Activity Relationship; Topoisomerase I and II inhibition; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Tumor Cells, Cultured; Topoisomerase I and II inhibition; Cytotoxicity; 2-(Thienyl-2-yl)-4-furyl-6-aryl pyridine; 2-(Thienyl-3-yl)-4-furyl-6-aryl pyridine
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.01.065

Designed and synthesized 48 2-thienyl-4-furyl-6-aryl pyridine derivatives were evaluated for their topoisomerase I and II inhibitory activity and cytotoxicity against several human cancer cell lines.
A series of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives were designed, synthesized, and evaluated for their topoisomerase I and II inhibition and cytotoxic activity against several human cancer cell lines. Compounds
10–
19 showed moderate topoisomerase I and II inhibitory activity and
20–
29 showed significant topoisomerase II inhibitory activity. Structure–activity relationship study revealed that 4-(5-chlorofuran-2-yl)-2-(thiophen-3-yl) moiety has an important role in displaying topoisomerase II inhibition.