2,4,6-Trisubstituted pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship.
Designed and synthesized were a series of pyridines substituted at 2, 4, and 6 positions with various 5- or 6-memberd heteroaromatics as antitumor agents. They were evaluated their topoisomerase I and II inhibitory activities along with cytotoxicities against several human cancer cell lines. Among the prepared compounds, 10-20 showed significant topoisomerase I or II inhibitory activities, and 21-26 showed considerable cytotoxicities against several human cancer cell lines. Structure-activity relationship study indicates that 4'-pyridine at 6-position of central pyridine plays a key role in biological activity.
Basnet
Arjun
A
College of Pharmacy, Yeungnam University, Kyongsan 712-749, Republic of Korea.
Thapa
Pritam
P
Karki
Radha
R
Na
Younghwa
Y
Jahng
Yurngdong
Y
Jeong
Byeong-Seon
BS
Jeong
Tae Cheon
TC
Lee
Chong-Soon
CS
Lee
Eung-Seok
ES
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011725:Pyridines; D059004:Topoisomerase I Inhibitors