Karki Radha, Song Chanju, Kadayat Tara Man, Magar Til Bahadur Thapa, Bist Ganesh, Shrestha Aarajana, Na Younghwa, Kwon Youngjoo, Lee Eung-Seok
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
Bioorg Med Chem. 2015 Jul 1;23(13):3638-54. doi: 10.1016/j.bmc.2015.04.002. Epub 2015 Apr 9.
A new series of thirty-six dihydroxylated 2,6-diphenyl-4-aryl pyridines containing hydroxyl groups at the ortho, meta, or para position of 2- and 6-phenyl rings attached to the central pyridine were designed and synthesized. They were evaluated for topoisomerase I and II inhibitory activity and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds with hydroxyl moiety either at the meta or para position of 2- or 6-phenyl ring in combination with thienyl or furyl group at 4-position of central pyridine displayed significant topoisomerase II inhibitory activity and cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for the compounds 9-11, 15-17, 19, 21-23, 28, and 41. Among all the synthesized compounds, compound 17 emerged as the most promising topoisomerase II inhibitor with significant cytotoxicity.
设计并合成了一系列新的36种二羟基化的2,6-二苯基-4-芳基吡啶，这些吡啶在连接于中心吡啶的2-和6-苯环的邻位、间位或对位含有羟基。对它们进行了拓扑异构酶I和II抑制活性以及对几种人类癌细胞系的细胞毒性评估，以开发新型抗癌药物。大多数在2-或6-苯环的间位或对位带有羟基部分且在中心吡啶的4-位带有噻吩基或呋喃基的化合物表现出显著的拓扑异构酶II抑制活性和细胞毒性。对于化合物9-11、15-17、19、21-23、28和41，观察到拓扑异构酶II抑制活性与细胞毒性之间存在正相关。在所有合成化合物中，化合物17成为最有前景的拓扑异构酶II抑制剂，具有显著的细胞毒性。
