Hydrazone-Functionalized <i>trans</i>-A<sub>2</sub>B‑Corroles: Effective Synergy\nin Photodynamic Therapy\nof Lung Cancer

A synthetic route to <i>trans</i>-A<sub>2</sub>B-corroles combining the macrocyclic\ncore with a hydrazone moiety, based on the reactivity of azoalkenes\ntoward dipyrromethanes, has been established with the aim of developing\na new class of photosensitizers for photodynamic therapy of lung cancer.\nThe study of the photophysical properties of the novel macrocycles\nallowed the identification of photosensitizers with absorption within\nthe phototherapeutic window and high singlet oxygen quantum yield.\nRelevant structure–photodynamic activity correlations were\nestablished by studying the new corroles-based photodynamic therapy\n(PDT) in human lung cancer cell lines (A549 and H1299). The methyl-hydrazone\ncorroles were more active than phenyl-hydrazone corroles, with the <i>N</i>-Boc and <i>N</i>-Ts groups being key structural\nfeatures to ensure high activity. The lead photosensitizers, with\nIC<sub>50</sub> values below 100 nM and no cytotoxicity per se, were\nsignificantly more active than 5,10,15-triphenylcorrole, showing that\nthe presence of the hydrazone functional group has a strong influence\non PDT activity.