The synthesis, photophysical behaviour and photosensitization ability of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused 5,15-diphenylchlorins against melanoma cells are described. All studied chlorins were found to be extremely active against melanoma cell lines A375 showing IC₅₀ values below 20 nM. Furthermore, a dihydroxymethyl diphenylchlorin was identified as an excellent candidate to allow modulating of different types of cell death, apoptosis vs. necrosis, by varying its concentration. This can be explored as a tool to improve the effectiveness of PDT since inflammatory response resulting from necrotic cell death after PDT can activate the antitumor immune response with implications also regarding the vascular damage. This feature combined with very low cytotoxicity against human melanoma cells in the absence of light activation and against human fibroblast HFF-1 cells makes this chlorin a candidate of choice as a photosensitizer for PDT. A comprehensive photophysical investigation including the determination of quantum yields for fluorescence, singlet oxygen sensitization and internal conversion, lifetimes and rate constants of all the excited state deactivation processes has been undertaken.

描述了新型的4,5,6,7-四氢吡唑并[1,5 - a ]吡啶融合的5,15-二苯基二氢卟酚对黑素瘤细胞的合成，光物理行为和光敏能力。发现所有研究的二氢卟酚对黑色素瘤细胞系A375具有极高的活性，显示出IC ₅₀值低于20 nM。此外，二羟甲基二苯基二氢卟酚被认为是极好的候选物，可以调节不同类型的细胞死亡，凋亡与凋亡。坏死，通过改变其浓度。可以探索将其作为提高PDT有效性的工具，因为PDT后坏死细胞死亡引起的炎症反应可以激活抗肿瘤免疫反应，并且还涉及血管损伤。该特征加上在没有光激活的情况下对人黑素瘤细胞和对人成纤维细胞HFF-1细胞的极低细胞毒性，使得该二氢卟酚成为PDT光敏剂的候选选择。已经进行了全面的光物理研究，包括确定荧光的量子产率，单线态氧敏化和内部转化，所有激发态失活过程的寿命和速率常数。