TY - JOUR
T1 - Synthesis and SAR study of new hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines as selective topoisomerase IIα-targeting anticancer agents
AU - Magar, Til Bahadur Thapa
AU - Seo, Seung Hee
AU - Kadayat, Tara Man
AU - Jo, Hyunji
AU - Shrestha, Aarajana
AU - Bist, Ganesh
AU - Katila, Pramila
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-2017R1A2B2003944 and NRF-2017R1D1A1B03027846 ).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/5/1
Y1 - 2018/5/1
N2 - As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds 8–18, 22, 24, and 25 showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3′-, or 4′-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2′-substitution.
AB - As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds 8–18, 22, 24, and 25 showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3′-, or 4′-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2′-substitution.
KW - 5H-Chromeno[4,3-b]pyridines
KW - Anticancer agents
KW - Hydroxyl and chlorine-substitution
KW - SAR study
KW - Selective topoisomerase IIα inhibition
UR - http://www.scopus.com/inward/record.url?scp=85042662932&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2018.02.035
DO - 10.1016/j.bmc.2018.02.035
M3 - Article
C2 - 29510948
AN - SCOPUS:85042662932
SN - 0968-0896
VL - 26
SP - 1909
EP - 1919
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 8
ER -