Photodynamic action of Pd(II)/porphyrin complexes against melanoma cells

IF 6.7 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2026-03-10 DOI:10.1016/j.ejmech.2026.118751

Edynara Cruz de Moraes , Marcos V. Palmeira-Mello , Lívia do Carmo Silva , Juliana Santana De Curcio , Alex Marchezini Graça , Jocely Lucena Dutra , Antonio Alonso , Guilherme Rocha Lino de Souza , Alzir Azevedo Batista , Elisângela de Paula Silveira-Lacerda , Pablo José Gonçalves

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Abstract

Photodynamic therapy (PDT) is an emerging strategy for cancer treatment and represents a promising approach for melanoma, one of the most aggressive and therapy-resistant forms of skin cancer. In this study, meso-tetra(4-pyridyl)porphyrin complexes coordinated with palladium(II)/diphosphine ligands (Porf@dppe, Porf@dppp, Porf@dppb, and Porf@dppf; dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1′-bis(diphenylphosphino)ferrocene), previously shown to display favorable lipophilicity and efficient singlet oxygen production, were evaluated against human (A375) and murine (B16-F10) melanoma cells, as well as non-cancerous keratinocytes (HaCaT). Cytotoxicity measured after a 90 min incubation period yielded dark IC₅₀ values between 0.6 and 8.6 μM, whereas light irradiation (λ = 415 nm, 1.8 J cm^-2, 36 mW cm^-2) resulted in markedly lower IC₅₀ values in the nanomolar range (2–27 nM). Irradiation increased intracellular ROS levels, induced morphological alterations in A375 cells, inhibited long-term proliferation, and reduced cell migration, particularly for Porf@dppb and Porf@dppf. The highest cytotoxicity was observed for Porf@dppf, likely due to the redox-active ferrocene unit promoting Fenton-type reactions and enhanced hydroxyl radical formation. Electron paramagnetic resonance (EPR) spin-trapping experiments confirmed light-induced generation of singlet oxygen, hydroxyl radicals, and superoxide anion, with significantly higher hydroxyl radical production observed for Porf@dppf. The photodynamic activity of these complexes is attributed to efficient ROS production involving simultaneous contributions from both Type I and Type II mechanisms. Moderate binding to bovine serum albumin suggests possible albumin-mediated plasma transport. Overall, palladium(II)/diphosphine porphyrin complexes emerge as promising photosensitizers for melanoma photodynamic therapy.

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Pd(II)/卟啉复合物对黑色素瘤细胞的光动力学作用

光动力疗法（PDT）是一种新兴的癌症治疗策略，代表了一种有希望的黑色素瘤治疗方法，黑色素瘤是最具侵袭性和治疗抗性的皮肤癌之一。在本研究中，中四（4-吡啶基）卟啉配合物与钯(II)/二膦配体(Porf@dppe, Porf@dppp， Porf@dppb和Porf@dppf；dppe = 1,2-二（二苯基膦）乙烷，dppp = 1,3-二（二苯基膦）丙烷，dppb = 1,4-二（二苯基膦）丁烷，dppf = 1,1 ' -二（二苯基膦）二烯铁)，先前显示出良好的亲脂性和高效的单线态产氧，对人（A375）和小鼠（B16-F10）黑色素瘤细胞以及非癌性角化细胞（HaCaT）进行了评估。90分钟孵育后的细胞毒性测量结果显示，暗IC50值在0.6 ~ 8.6 μM之间，而光照射（λ = 415 nm, 1.8 J cm-2, 36 mW cm-2）在纳米摩尔范围（2 ~ 27 nm）内的IC50值明显降低。辐照增加细胞内ROS水平，诱导A375细胞形态学改变，抑制长期增殖，减少细胞迁移，尤其是Porf@dppb和Porf@dppf。Porf@dppf的细胞毒性最高，可能是由于具有氧化还原活性的二茂铁单元促进芬顿型反应和增强羟基自由基的形成。电子顺磁共振（EPR）自旋捕获实验证实了光诱导单线态氧、羟基自由基和超氧阴离子的产生，并观察到Porf@dppf中羟基自由基的产生明显增加。这些复合物的光动力学活性归因于有效的ROS生成，涉及I型和II型机制的同时贡献。与牛血清白蛋白的适度结合提示可能是白蛋白介导的血浆转运。总的来说，钯(II)/二膦卟啉复合物是黑色素瘤光动力治疗中有前途的光敏剂。

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.