Betulinic acid derivatives in melanoma therapy: pharmacological assessment in a preclinical approach

Melanoma is the deadliest form of skin cancer owing to its metastatic potential. In this study, the anticancer effects of Betulinic Acid (BA) derivatives were evaluated in melanoma models. The in vitro cytotoxic effect on B16-F10 (melanoma), VERO (kidney of adult African green monkey), and Hep-2 (laryngeal tumour) cells was determined using the MTT assay. Flow cytometry analysis was used to evaluate non-adherent human lymphocytes. The in vivo assay was performed on B16-F10 tumour bearing C57BL/6 mice. The BA derivatives oxime (3) and amine (4) showed the most significant cytotoxicity against B16-F10 cells, with IC50 3.2 and 12.4 µM, respectively, without statistically significant effects on healthy cells, and cell death mechanism involving apoptosis. In vivo, these derivatives led to approximately 90% tumour regression at 1.5 mg/kg when compared to the control group. These findings indicate that BA derivatives exhibit higher chemotherapeutic potential in melanoma cells than unmodified BA does.