TY - JOUR
T1 - Hydroxylated 2,4-diphenyl indenopyridine derivatives as a selective non-intercalative topoisomerase catalytic inhibitor
AU - Kadayat, Tara Man
AU - Park, Chanmi
AU - Jun, Kyu Yeon
AU - Thapa Magar, Til Bahadur
AU - Bist, Ganesh
AU - Yoo, Han Young
AU - Kwon, Youngjoo
AU - Lee, Eung Seok
N1 - Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 ).
Publisher Copyright:
© 2014 Elsevier Masson SAS.
PY - 2015/1
Y1 - 2015/1
N2 - For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.
AB - For the development of novel anticancer agents, we designed and synthesized hydroxylated 2,4-diphenyl indenopyridines, and evaluated their topoisomerase inhibitory activity as well as their antiproliferative activities against several human cancer cell lines. The structure-activity relationship study showed that indenopyridines with hydroxyl group at meta or para positions of 2-or 4-phenyl ring displayed selective and significant topoisomerase IIα (topo IIα) inhibitory activity and potent antiproliferative activity. Positive correlation between topo IIα inhibition and antiproliferative activity was observed for compounds 15, 16, 18-20, 22, 23, 25 and 26. The mode of action of compound 16 was further evaluated to be a non-intercalativetopo IIα catalytic inhibitor.
KW - Anticancer agents
KW - Hydroxylated 2,4-diphenyl indenopyridine
KW - Terpyridine
KW - Topoisomerase IIa non-intercalative
KW - catalytic inhibitorAntiproliferative activity
UR - http://www.scopus.com/inward/record.url?scp=84912137514&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2014.11.046
DO - 10.1016/j.ejmech.2014.11.046
M3 - Article
C2 - 25437617
AN - SCOPUS:84912137514
SN - 0223-5234
VL - 90
SP - 302
EP - 314
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -