Efficient Synthesis of Fluorinated Derivatives from Isolated 24-Ethyl cholest-5-en-3β-ol: Characterization, Quantum Chemical Calculations by DFT and Molecular Docking

Abstract

The current work focuses on the synthesis, characterization and docking study of two new fluorine containing steroidal esters, viz. 1a (3-β-(4-fluoro benzoyloxy)stigmast-5-en) and 1b (3-β-(2-fluoro benzoyloxy)stigmast-5-en). Synthesis of compounds 1a and 1b was done by conjugating β-sitosterol (1) with 4-fluorobenzoic acid and 2-fluorobenzoic acid, respectively using high yielding Steglich esterification method and their structures were identified using ¹H NMR, FT-IR and UV spectroscopy as well as mass spectrometry. Docking studies of compounds 1, 1a and 1b assisted in evaluating the inhibitory effect of these steroids against the 2ITO a lung cancer protein. The ΔG values (binding energy) of all the compounds revealed that synthetic derivatives 1a (with binding energy –9.6 Kcal/mol) and 1b (with binding energy –9.5 Kcal/mol) are more potent than the parent molecule, compound 1 (with binding energy –7.5 Kcal/mol). A comparative atoms in molecules (AIM) studies predicted greater stability of compound 1b over 1a. High value of β₀ of 1a (4.1 × 10^–30 esu) suggested that they may be used as NLO materials.