Synthesis, characterization, and evaluation of diosgenin nicotinate as a potential antioxidant and antileishmanial agent

The toxicity and the side effects of most drugs that are clinically used for leishmaniasis led scientists all over the world to search for a new source of antileishmanial drugs. Chemical modification of naturally occurring plant compounds was one of the most important choices as an alternative to traditionally pentavalent antimony-based drugs. This study aimed to modify the structural properties of steroidal diosgenin (DG) through esterification with nicotinic acid (NA) using the Steglich method. The identification and purity of diosgenin nicotinate (DGNA) were confirmed by thin-layer chromatography (TLC), Fourier-transform infrared spectroscopy (FT-IR), and 1 H nuclear magnetic resonance spectroscopy ( 1 H NMR). The effect of dimethylaminopyridine (DMAP) initial concentration on the yield of DGNA was performed. The higher yield (91%) was achieved for the use of (0.5 mM) of DMAP as reaction catalyst. The antioxidant capacity and in vitro antileishmanial activity of DGNA were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay and the MTT assay, respectively. The results showed that modified diosgenin (DGNA) showed a higher antioxidant activity (IC 50 = 71.75 mM) than DG (IC 50 = 125.8 mM), and exhibited greater biological effect against L. tropica leishmaniasis (IC 50 = 0.532 mM) compared to DG (IC 50 = 1.24 mM). These results indicate potential antileishmanial and antioxidant activity of DGNA and encourage further in vivo research.