Dihydroxylated 2,4,6-triphenyl pyridines: synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study.
Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. 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. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.
College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
Radha
R
Karki
Pritam
P
Thapa
Han Young
HY
Yoo
Tara Man
TM
Kadayat
Pil-Hoon
PH
Park
Youngwha
Y
Na
Eunyoung
E
Lee
Kyung-Hwa
KH
Jeon
Won-Jea
WJ
Cho
Heesung
H
Choi
Youngjoo
Y
Kwon
Eung-Seok
ES
Lee
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011725:Pyridines; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II