Evaluating Naphthalene-Modified Metallosalen Complexes as Anticancer Agents

The development of novel naphthalene-modified metallosalens incorporating Pt(II) and Pd(II) presents a promising approach to addressing limitations in cancer therapies. These metallosalens were synthesized and characterized using single crystal X-ray diffraction (sc-XRD), UV–vis spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and C, H, N elemental analysis. Their strong metal coordination and enhanced electronic interactions, stemming from π-conjugated aromatic structures, improved their DNA-binding affinity and cytotoxic efficacy. Biological assays confirmed significant cytotoxicity in A375 (melanoma) and H292 (nonsmall cell lung cancer) cell lines, while demonstrating minimal toxicity toward HSAEC healthy lung cells. PtL1 and PtL2 exhibited superior activity, inducing apoptosis with high selectivity for cancer cells, as validated by Incucyte Caspase-3/7 Green Dye assays. These findings highlight the potential of naphthalene-modified metallosalens as broad-spectrum cancer therapies, balancing efficacy with reduced off-target effects, and underscore the importance of ligand design and metal coordination in advancing next-generation chemotherapeutics.