Porphyrin-ligustrazine conjugates: Dual-mode therapeutic agents combining photodynamic and chemotherapy for enhanced antitumor activity

Dual-mode therapeutic strategies have demonstrated substantially greater efficacy than single-modality treatments and hold broad clinical potential. In this study, we developed a series of 20 novel ligustrazine–porphyrin derivatives by integrating porphyrin-based photodynamic therapy (PDT) with ligustrazine chemotherapy. UV–vis spectroscopy confirmed that the characteristic photophysical features of porphyrins, including the Soret and Q bands, remained unchanged after conjugation with ligustrazine. Reactive oxygen species (ROS) detection assays revealed that all compounds were capable of generating ROS, with production further enhanced upon coordination with Zn(II). The derivatives exhibited varying levels of antitumor activity against HGC-27, A549, DU145, TCCSUP, HCT-116, and MDA-MB-231 cancer cell lines under both light and dark conditions, while demonstrating relatively lower cytotoxicity toward normal H9C2 cells. Among these compounds, derivative 8d showed the most pronounced antitumor activity.