TY - JOUR
T1 - Synthesis and structure-activity relationships of hydroxylated and halogenated 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols as selective topoisomerase IIα inhibitors
AU - Thapa Magar, Til Bahadur
AU - Hee Seo, Seung
AU - Shrestha, Aarajana
AU - Kim, Jeong Ahn
AU - Kunwar, Surendra
AU - Bist, Ganesh
AU - Kwon, Youngjoo
AU - Lee, Eung Seok
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - The objective of this study was to discover potential topoisomerase (topo) targeting anticancer agents. Novel series of hydroxylated and halogenated (-F, -Cl, and -CF3) 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were systematically designed and synthesized by faster, economic, and environmentally friendly l-proline catalyzed and microwave-assisted one pot reaction method. The synthesized compounds were assessed for topo I and IIα inhibitory and anti-proliferative activities. The in vitro evaluation displayed that most of the compounds have selective topo IIα inhibitory activity as well as selectivity towards T47D human cancer cell line. Structure-activity relationship study suggested that the introduction of additional hydroxyl functionality at 7-positon of benzofuro[3,2-b]pyridine skeleton is crucial for selective topo IIα inhibitory activity. Placement of phenolic moiety on the 4-position of the tricyclic system imparts better topo IIα inhibitory and anti-proliferative activity.
AB - The objective of this study was to discover potential topoisomerase (topo) targeting anticancer agents. Novel series of hydroxylated and halogenated (-F, -Cl, and -CF3) 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were systematically designed and synthesized by faster, economic, and environmentally friendly l-proline catalyzed and microwave-assisted one pot reaction method. The synthesized compounds were assessed for topo I and IIα inhibitory and anti-proliferative activities. The in vitro evaluation displayed that most of the compounds have selective topo IIα inhibitory activity as well as selectivity towards T47D human cancer cell line. Structure-activity relationship study suggested that the introduction of additional hydroxyl functionality at 7-positon of benzofuro[3,2-b]pyridine skeleton is crucial for selective topo IIα inhibitory activity. Placement of phenolic moiety on the 4-position of the tricyclic system imparts better topo IIα inhibitory and anti-proliferative activity.
KW - Anti-proliferative activity
KW - Benzofuro[3,2-b]pyridin-7-ol
KW - Halogen moiety
KW - Hydroxyl moiety
KW - Structure-activity relationship
KW - Topoisomerase inhibition
UR - http://www.scopus.com/inward/record.url?scp=85104152567&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2021.104884
DO - 10.1016/j.bioorg.2021.104884
M3 - Article
C2 - 33872925
AN - SCOPUS:85104152567
SN - 0045-2068
VL - 111
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 104884
ER -