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

A series of fourteen trans-AB-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).

Hydrazone-Functionalized -AB-Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer.

A synthetic route to -AB-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).

Ring-Fused -Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation.

Novel 4,5,6,7-tetrahydropyrazolo[1,5-]pyridine-fused -tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers' performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from -tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC values of 68 and 344 nM against A375 cells, respectively.

Novel fluorinated ring-fused chlorins as promising PDT agents against melanoma and esophagus cancer.

Investigation of novel 4,5,6,7-tetrahydropyrazolo[1,5-]pyridine-fused chlorins, derived from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, as PDT agents against melanoma and esophagus cancer is disclosed. Diol and diester fluorinated ring-fused chlorins, including derivatives with 2-(2-hydroxyethoxy)ethanamino groups at the phenyl rings, were obtained a two-step methodology, combining SAr and [8π + 2π] cycloaddition reactions. The short-chain PEG groups at the -position of the phenyl rings together with the diol moiety at the fused pyrazole ring promote a red-shift of the Soret band, a decrease of the fluorescence quantum yield and an increase of the singlet oxygen formation quantum yield, improving the photophysical characteristics required to act as a photosensitizer.