Melanoma is a very aggressive type of
skin cancer. Mutation in BRAF and NRAS are often found in patients with this disease. Therefore, in recent years the search for new molecules that inhibit these
proteins has been intensified. After many years with no new treatments for
melanoma, the U.S. Food and Drug Administration (FDA) recently approved
vemurafenib. However, many patients have already acquired resistance and have experienced severe side effects. Therefore, this work aims to evaluate a new set of compounds including allylic
isothiouronium salts (1, 2 and 3), N-phenyl-substituted analog (4) and isothiosemicarbazide
salts (5 and 6) for their potential antimelanoma activity. To this end, viability assay, cell cycle analysis, expression of NRAS and BRAF, as well as migration and invasion assay were performed with different
melanoma cell lines.
Isothiouronium salts 1-3 presented CC50 (concentration required to reduce the cell number by 50%) in a range of 7-28 μM. Furthermore,
salt 1 significantly decreased the expression of NRAS. However, cells incubated with these
salts did not disturb the cell cycle phases; instead, an increase in the number of apoptotic cells was observed. Regarding potential antiinvasion effects, both 1 and 2 prevented cell migration as well as cell invasion. Finally, when
salts 1 and 2 were associated with
vemurafenib, a marked decrease in cell viability was observed when compared to the compounds incubated alone. Briefly, the
salts exhibited interesting results, especially 1, which decreased the expression of NRAS, increased apoptotic cells and, when combined with
vemurafenib, resulted in a synergistic effect. Therefore, we intend to test compound 1 in pre-clinical studies.