Hydrazone-Functionalized trans-A2B‑Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer

A synthetic route to trans-A2B-corroles combining the macrocyclic core with a hydrazone moiety, based on the reactivity of azoalkenes toward dipyrromethanes, has been established with the aim of developing a new class of photosensitizers for photodynamic therapy of lung cancer. The study of the photophysical properties of the novel macrocycles allowed the identification of photosensitizers with absorption within the phototherapeutic window and high singlet oxygen quantum yield. Relevant structure–photodynamic activity correlations were established by studying the new corroles-based photodynamic therapy (PDT) in human lung cancer cell lines (A549 and H1299). The methyl-hydrazone corroles were more active than phenyl-hydrazone corroles, with the N-Boc and N-Ts groups being key structural features to ensure high activity. The lead photosensitizers, with IC50 values below 100 nM and no cytotoxicity per se, were significantly more active than 5,10,15-triphenylcorrole, showing that the presence of the hydrazone functional group has a strong influence on PDT activity.