College of Pharmacy, Yeungnam University, Kyongsan 712-749, Republic of Korea.
Bioorg Med Chem. 2010 Jan 1;18(1):377-86. doi: 10.1016/j.bmc.2009.10.049. Epub 2009 Oct 29.
Designed and synthesized 60 2-thienyl-4-furyl-6-aryl pyridine derivatives were evaluated for their topoisomerase I and II inhibitory activities at 20 microM and 100 microM and cytotoxicity against several human cancer cell lines. Compounds 8, 9, 11-29 showed significant topoisomerase II inhibitory activity and compounds 10 and 11 showed significant topoisomerase I inhibitory activity. Most of the compounds (7-21) possessing 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety showed higher or similar cytotoxicity against HCT15 cell line as compared to standards. Most of the selected compounds displayed moderate cytotoxicity against MCF-7, HeLa, DU145, and K562 cell lines. Structure-activity relationship study revealed that 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities.
设计并合成了 60 种 2-噻吩基-4-呋喃基-6-芳基吡啶衍生物，在 20μM 和 100μM 下评估了它们对拓扑异构酶 I 和 II 的抑制活性以及对几种人癌细胞系的细胞毒性。化合物 8、9、11-29 表现出显著的拓扑异构酶 II 抑制活性，化合物 10 和 11 表现出显著的拓扑异构酶 I 抑制活性。大多数具有 2-(5-氯噻吩-2-基)-4-(呋喃-3-基)部分的化合物（7-21）对 HCT15 细胞系的细胞毒性比标准品更高或相似。大多数选定的化合物对 MCF-7、HeLa、DU145 和 K562 细胞系表现出中等的细胞毒性。构效关系研究表明，2-(5-氯噻吩-2-基)-4-(呋喃-3-基)部分在显示生物活性方面起着重要作用。
