Synergistic Effects in PtII-Porphyrinoid Dyes as Candidates for a Dual-Action Anticancer Therapy: A Theoretical Exploration
Synergistic Effects in PtII-Porphyrinoid Dyes as Candidates for a Dual-Action Anticancer Therapy: A Theoretical Exploration
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DOI：
10.1002/chem.201702876
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发表时间：
2017-10-26
影响因子：
4.3
通讯作者：
Adamo, Carlo
中科院分区：
文献类型：
--
作者：
Alberto, Marta Erminia;Adamo, Carlo
光敏剂（PS）与顺铂样单位的组合代表了一种具有挑战性的策略，以提高光动力疗法的有效性，并提供双重作用的抗癌治疗。最近，新的四-铂-II-卟啉共轭物已被提出作为有前途的多靶点药物。为了揭示Pt-II中心对PS的化学和物理性质的影响，并探索PS对Pt-II配体在到达其生物靶标之前的活化机制的影响，我们对这些四-Pt-II-卟啉缀合物进行了第一性原理研究。为了在这一新的领域提出进一步的进展，并获得有用的见解，设计新的，更有效的Pt-II-PS共轭物，我们引入结构修饰的卟啉染料，其中涉及的四-Pt-II-二氢卟酚和四-Pt-II-菌绿素衍生物的合成。结果表明，所设计的染料更好地满足了在双重作用疗法中成功的标准，因为它们显示出改善的光学性质并降低了Pt-II部分的水解速率，后者是避免缀合物在其运输到生物靶标期间的许多副反应的理想特征。
The combination of a photosensitizer (PS) with a cisplatin-like unit represents a challenging strategy to increase the effectiveness of photodynamic therapy and to afford a dual-action anticancer treatment. Recently, new tetra-Pt-II-porphyrin conjugates have been proposed as promising multitarget agents. To reveal the effect of the Pt-II center on the chemical and physical properties of the PS and to explore the effect of the PS on the activation mechanism of Pt-II ligand before reaching its biological target, we carried out a first-principle investigation on these tetra-Pt-II-porphyrin conjugates. To propose a further advance in this novel field and to gain useful insights for the design of new, more efficient Pt-II-PS conjugates, we introduced structural modifications into the porphyrin dye, which involved the synthesis of the tetra-Pt-II-chlorin and tetra-Pt-II-bacteriochlorin derivatives. Results showed that the designed dyes better met the criteria to be successful in a dual-action therapy, as they displayed improved optical properties and reduced the hydrolysis rate of the Pt-II moiety, the latter being a desirable feature to avoid many side reactions of the conjugate during their transport to the biological target.