Cytotoxicity and DNA Damage Ability of Isomeric <i>meso</i> -Tetra(cisplatin)porphyrins in Keratinocytes and Melanoma Cells Treated with Photodynamic Therapy

In this study, we evaluated and compared the cytotoxicity and DNA damage-inducing effects of two porphyrins conjugated with cisplatin at two different positions on the pyrrolic rings (3-cis-PtTPyP and 4-cis-PtTPyP) with free cisplatin after exposure to white light. Both porphyrin molecules induced DNA damage and cytotoxic effects at lower concentrations (0.5–5 μM) when exposed to light. These molecules were more cytotoxic than free cisplatin to the human melanoma cell line exposed to white light since the observed IC50 values were 2.02 μM (3-cis-PtTPyP), 2.12 μM (4-cis-PtTPyP), and 13.25 μM (cisplatin). In addition, the results indicate that the treatment with these cisplatin-porphyrins followed by white light exposure was more cytotoxic to the melanoma cell line than to the keratinocyte cell line. Furthermore, both porphyrins presented higher DNA damage ability than free cisplatin, with 3-cis-PtTPyP being the most genotoxic. It was also observed that both cisplatin-porphyrins significantly denatured egg albumin under light exposure, indicating a potential protein denaturation ability. Additionally, in silico analyses generated significant insights regarding the toxicological characteristics of both cisplatin-porphyrin compounds and their safety regarding clinical use. These findings demonstrate the effects of these cisplatin-conjugated porphyrins and highlight their differences from the conventional chemotherapeutic cisplatin.