TY - JOUR
T1 - Dihydroxylated 2,4,6-triphenyl pyridines
T2 - Synthesis, topoisomerase i and II inhibitory activity, cytotoxicity, and structure-activity relationship study
AU - Karki, Radha
AU - Thapa, Pritam
AU - Yoo, Han Young
AU - Kadayat, Tara Man
AU - Park, Pil Hoon
AU - Na, Youngwha
AU - Lee, Eunyoung
AU - Jeon, Kyung Hwa
AU - Cho, Won Jea
AU - Choi, Heesung
AU - Kwon, Youngjoo
AU - Lee, Eung Seok
N1 - Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0066925 , 2010-0002646 , and 2011-0001170 ).
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Anticancer agents
KW - Cytotoxicity
KW - Dihydroxylated 2,4,6-triphenyl pyridines
KW - Topoisomerase I
KW - Topoisomerase I.I.
UR - http://www.scopus.com/inward/record.url?scp=84857239566&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2012.01.015
DO - 10.1016/j.ejmech.2012.01.015
M3 - Article
C2 - 22318164
AN - SCOPUS:84857239566
SN - 0223-5234
VL - 49
SP - 219
EP - 228
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -