DPAP

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 IC50 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 IC50 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.

Cu²⁺ is an essential trace element for the organism, but its excess can also cause irreversible damage to the organism. As such, a "Turn-Off" fluorescent probe DPAP for the specific detection of Cu²⁺ was successfully constructed. DPAP exhibits large Stokes shift (120 nm), fast reaction speed (1 min), low detection limit (15.2 nM), low toxicity, and good cell permeability. Cu²⁺ quenches the fluorescence of DPAP by blocking its intramolecular charge transfer process to achieve the detection of Cu²⁺ and has been confirmed by HRMS, ¹H NMR and DFT calculations. Excitingly, the five-cycle detection of Cu²⁺ and the successful recovery of trace Cu²⁺ in environmental water samples fully demonstrate the potential of DPAP for practical applications. In particular, DPAP can observe the distribution and translocation patterns of exogenous Cu²⁺ in HeLa cells and zebrafish in real-time. This research concept has offered important theoretical support for the study of the environmental behavior of heavy metal ions.