Topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of dihydroxylated 2,6-diphenyl-4-aryl pyridines.
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.
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Radha
R
Karki
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
Chanju
C
Song
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Tara Man
TM
Kadayat
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Til Bahadur Thapa
TB
Magar
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Ganesh
G
Bist
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Aarajana
A
Shrestha
College of Pharmacy, Cha University, Pochon 487-010, Republic of Korea.
Younghwa
Y
Na
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
Youngjoo
Y
Kwon
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@yu.ac.kr.
Eung-Seok
ES
Lee
D000951:Antigens, Neoplasm / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II
Anticancer agents; Cytotoxicity; Dihydroxylated 2,6-diphenyl-4-aryl pyridines; Topoisomerase I; Topoisomerase II