Exploration of 24-Hydroxylase, a vitamin D metabolizing enzyme through in silico screening of some new phenylalanine-benzofuran-acetamide/ propanamide/butanamide hybrids: An approach to overcome vitamin D deficiency

Phenylalanine-benzofuran-acetamide/propanamide/butanamide hybrids (VIa-b/VIIa-b/ VIIIa-b) were synthesized and in silico screening for CYP24A1 inhibitory activity was studied. The most promising compound among all was found to be VIa (binding score-7.6), binds in manner very similar to the calcitriol. The carboxylate and-NH group forms two hydrogen bonds with THR394 and THR395, respectively. The ring benzofuran fits into the hydrophobic pocket and forms T-shaped π-π stacking, whereas the terminal benzyl ring forms π-sigma interaction with the ILE131 residue. These results clearly showed that these benzofuran hybrids could be a promising lead in the development of novel CYP24A1 inhibitors.