Highlights

New series of -OH, -Cl, -F, and -CF₃ containing 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were prepared.

Utilized rapid, economic, and environment friendly one-pot synthetic method.

Majority of compounds showed selective topo IIα inhibitory activity.

Hydroxyl at 7-position and phenol group on the 4-position of the tricyclic system is important for activity.

Abstract

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.