Novel dibenzoylmethane derivative 2-allyl-1,3-diphenyl-1, 3-propanedione: a safe and effective topical treatment for melanoma.

Abstract

This study investigated 2-allyl-1,3-diphenyl-1,3-propanedione (DPAP), a dibenzoylmethane derivative, as a potentially more effective and safer alternative to dacarbazine for melanoma treatment. The antitumor activity of DPAP was assessed through comprehensive in-vitro, in-silico, and in-vivo experiments. In-vitro assays evaluated DPAP's IC 50 values against melanoma cells, benchmarking its efficacy against dacarbazine. Molecular analyses explored apoptosis mechanisms, emphasizing the roles of FAS receptors and caspase pathways. In-silico absorption, distribution, metabolism, excretion, and toxicity analysis provided insights into DPAP's pharmacokinetic profile, including absorption, distribution, metabolism, and toxicity. In-vivo studies examined its effects on tumor volume, vascular endothelial growth factor (VEGF) levels, and the histopathology of the liver, kidney, and lymph nodes. DPAP demonstrated significantly enhanced antitumor activity, reflected by markedly lower IC 50 values compared with dacarbazine, underscoring its superior efficacy and specificity toward tumor cells. Molecular assays confirmed that DPAP induces apoptosis through modulation of FAS receptors and activation of caspase pathways. In-silico results revealed favorable pharmacokinetic properties, including high intestinal absorption and good tissue distribution, with no evidence of carcinogenic potential. Notably, in-vivo experiments showed that DPAP effectively reduced tumor volume and VEGF levels, while also preventing hepatotoxicity and nephrotoxicity. In addition, it inhibited the migration of tumor cells to lymph nodes. These findings position DPAP as a promising candidate for melanoma treatment, particularly as a topical therapeutic, offering enhanced efficacy and safety compared with existing treatments. DPAP is a promising candidate for melanoma treatment, particularly through topical application, offering a safer and more effective alternative to current treatments.