Design, synthesis and characterization of novel cholesterol derivatives: Anti-cancer activity, ADMET profiling and DFT insights.

In the present work, Steglich esterification and Mizoroki-Heck reaction have been carried out for the synthesis of novel cholesterol derivatives. The synthesized derivatives 2, 3, 4, 5 and 6 were purified through column chromatography and characterized by 1H, 13C NMR, FT-IR spectroscopy, and mass spectrometry. The geometries of all the compounds were optimized in the ground state by the density function theory at the B3LYP/6-31G(d,p) level. The in vitro evaluation of compounds 2 (IC50 17), 3 (IC50 11), 4 (IC50 14) and 6 (IC50 20) for their anti-cancer activity against SiHa cells demonstrated an increased apoptotic activity in comparison to the parent compound 1 (IC50 24) i.e. cholesterol. The Molecular docking studies were carried out against two proteins bearing the protein data bank (PDB) ID 2B9D and 1R9W to investigate the inhibitory action of the derivatives. The result of molecular docking showed appreciable interactions of 2, 3, 4, 5 and 6 with the selected proteins as compared to 1. The in vitro and molecular docking studies show that the synthesized molecules can prove to be better anti-cancer agents on other cancer cells also. The computational analysis data and the experimental data were in conformation with each other. ADMET analysis was carried out using the admetSAR database and Swiss ADME.