Design, Synthesis and Biological Evaluation of Novel Capsaicin Analogues Containing Heterocyclic Fatty Acids

Abstract

There is an urgent need to study safe and biocompatible medicinal compounds which necessitates the discovery of new agents from simple natural starting materials. In this study, eight novel capsaicin derivatives have been synthesized by combination of oxadiazole containing fatty acids with vanillyl amide. All the compounds were characterized by spectral analysis and were examined for their cytotoxicity, antimicrobial, antioxidant and anti-inflammatory properties. The antioxidant activity of the synthesized derivatives was evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and thiobarbituric acid reactive substances (TBARS) assays. All of the synthesized derivatives have exhibited significant antioxidant activity in comparison to butylated hydroxy toluene (BHT) which is used as a reference antioxidant. The novel capsaicin derivatives with nitro (8 e) and methoxy substituents (8 f, 8 g and 8 h) exhibited the most significant antioxidant activity compared with BHT. In cytotoxicity assay against three cell lines, the derivative with bromo substituent showed excellent activity against B16-melanoma cancer cell line followed by nitro and methoxy analogs which showed promising activity against HepG2- hepato and DU145-prostate cancer cell lines respectively. In addition, all the derivatives exhibited moderate broad spectrum antibacterial, antifungal and anti-inflammatory activity.