Yb(OTf)3 catalysed synthesis of thiochromeno[2,3-b]chromene and their anti-proliferative study

The synthesis of hitherto unreported thiochromeno[2,3-b]chromene from 4-hydroxy-2H-chromene-2-thione is investigated with salicylaldehydes and cylohexane-1,3-dione in the presence of 10 mol% Yb(OTf)3 in toluene. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with salicylaldehyde followed by Michael addition with 4-hydroxy-2H-chromene-2-thione. The products were obtained in good to excellent yields, with retention of sulphur atoms in the heterocycle. This synthetic approach offers a straightforward and reliable method for preparing sulfur-containing heterocycles, potentially expanding the scope of thiochromene chemistry. A molecular docking study was performed on all synthesized derivatives, and two compounds demonstrated a dose-dependent anti-proliferative effect and enhanced ROS generation in the MDA-MB-468 TNBC breast cancer cell lines.

Publication History

Received: 29 April 2025

Accepted: 14 May 2025

Accepted Manuscript online:
14 May 2025