Antioxidant activity of novel diosgenin derivatives: Synthesis, biological evaluation, and in silico ADME prediction

Abstract

A series of novel diosgenin (DSG) derivatives has been synthesized and tested in vitro for their antioxidant activity. Initially, four analogues have been evaluated for their cytotoxicity using normal human skin fibroblast (NHDF) as model cells. As a result, 84% of NHDF cells were still alive at 5 µM, so these compounds can be considered as innoxious to fibroblasts at this concentration. Then, hemolytic activity against human erythrocytes was studied in order to evaluate the potential impact of tested compounds against normal host cells. The result < 5% of hemolysis rates suggest no lytic activity for most compounds. After that, the main test - evaluation the antioxidant effect of DSG and its new derivatives against lipid peroxidation in the o/w emulsion model - was performed. The most promising compound (8) exhibited the significant antioxidant activity and the biocompatibility towards normal human dermal fibroblasts and red bloods cells. This p-aminobenzoic derivative revealed 61.6% blocking of induced lipid oxidation. Furthermore, eleven predicted ADME properties were predicted for all tested compounds and revealed that they are in compliance with drug-likeness criteria.

Keywords: ADME; Antioxidant activity; Diosgenin; Diosgenin derivatives.