A novel dibenzoylmethane derivative (IDPIP) impairs melanoma cell migration and selectively induces apoptosis in vitro.

Melanoma remains one of the most aggressive forms of skin cancer, with limited therapeutic options and significant treatment-related toxicity. In this study, we evaluated the biological activity of a novel dibenzoylmethane derivative, IDPIP, focusing on its cytotoxic, anti-migratory, and pro-apoptotic effects in melanoma cells. IDPIP exhibited pronounced and selective cytotoxicity in murine and human melanoma cell lines, with significantly lower toxicity to non-tumor cells. Notably, IDPIP demonstrated greater potency and selectivity than a clinically used chemotherapeutic agent, with a selectivity index of 23.44, indicating a more favorable therapeutic window. Morphological and flow cytometric analyses revealed that IDPIP induces apoptosis in a dose-dependent manner (up to 90% mortality), involving activation of both intrinsic and extrinsic pathways, as evidenced by caspase-9 and caspase-8 activation assay, respectively. In addition to its cytotoxic effects, IDPIP impaired melanoma cell migration and invasion in vitro, as demonstrated by PMA-induced wound-healing and transwell assays. Treated cells exhibited morphological alterations consistent with reduced adhesion and cytoskeletal disruption. IDPIP treatment was also associated with the accumulation of autophagy-related vesicular structures in this process. Furthermore, using optical tweezers, we demonstrated that IDPIP is capable of interacting with the minor groove of double-stranded DNA. This interaction may contribute to cellular stress responses associated with apoptosis and impaired cell motility. In summary, IDPIP exhibits selective cytotoxicity, promotes apoptosis, and impairs melanoma cell migration in vitro, supporting its potential as a promising candidate for further investigation. Additional studies, including evaluation of DNA damage response pathways and in vivo models, will be necessary to fully elucidate its mechanism of action and therapeutic relevance.