trans-A2B-Corroles containing an oxime moiety: Novel photosensitizers for photodynamic therapy of lung cancer

A series of fourteen trans-A₂B-corroles containing an oxime moiety were synthesized based on the reactivity of nitrosoalkenes towards dipyrromethanes, to evaluate their potential as a safe therapeutic option for photodynamic therapy (PDT) of lung cancer (LC). These macrocycles exhibited photophysical and acid-base properties suitable for use as photosensitizers (PS) in biological systems. Structure-photodynamic activity relationships were established by evaluating the photodynamic effects of the compounds on human lung cancer cell lines (A549 and H1299). The strong photodynamic activity observed demonstrated that the oxime group plays a crucial role in enhancing biological activity. In fact, the model corrole without an oxime moiety (5,10,15-triphenylcorrole) showed no photodynamic activity against any of the studied LC cell lines (IC₅₀ > 10 μM), whereas all fourteen oxime-functionalized corroles exhibited significantly lower IC₅₀ values. Among them, triazole-oxime derivatives displayed the highest activity, followed by phenyl-oxime and methyl-oxime corroles. The lead photosensitizers, with IC₅₀ values below 50 nM and no cytotoxicity per se, outperformed Temoporfin, the active compound in Foscan®, a clinically approved PS. This highlights oxime-functionalized trans-A₂B-corroles as promising candidates for photodynamic therapy of LC. The in vivo efficacy of one oxime-corrole based PDT was also evaluated using the chick embryo chorioallantoic membrane model demonstrating its potential as an effective photosensitizer in vivo.