SYNTHESIS, MOLECULAR DOCKING AND BIOLOGICAL EVALUATION OF STEROIDAL CYTOTOXIC AGENTS

Steroidal chalcones, hybrid molecules possessing characteristics of both, a steroid and a chalcone, have drawn the interest of researchers exhibiting potential biological activities and pharmacological properties. In continuation, of our previous research wherein steroidal derivatives were synthesized and evaluated, 20 steroidal chalcones were designed and screened for inhibition of HhSP targeting the Smoothened receptor (PDB ID: 4JKV) by preliminary molecular docking analysis using AutoDock tools with Cygwin 64 terminal software. Out of these, 9 steroidal chalcones showing the best dock score were synthesized, purified, and characterized by spectral analysis. Synthesized compounds were biologically evaluated by in vivo antiangiogenic activity (CAMs assay) and in vitro cytotoxic activity using HOP-62 lung cancer cell line (SRB assay). Docking analysis results indicated favorable binding interactions of the designed compounds compared to the co-crystallized ligand. In vivo biological evaluation and in vitro cytotoxicity evaluation demonstrated promising activity of compound 3d (3-(3,4-dimethoxyphenyl)- 1-(3-hydroxy-pregna-5-en-17-yl)-2-propen-1-one). Thus, compound 3d holds the potential to act as a cytotoxic agent against lung cancer, with Smo receptor inhibition likely being the mode of action.