铂类抗癌药物研发的进展:战略、发现和未来展望的全面回顾

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2024-08-23 DOI:10.1016/j.bmc.2024.117894
Debsankar Sahoo , Priya Deb , Tamal Basu , Srishti Bardhan , Sayan Patra , Pradip K. Sukul
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引用次数: 0

摘要

铂类抗癌药物一直处于癌症化疗的前沿,顺铂是治疗各种恶性肿瘤的先驱。这篇综述文章全面概述了铂类抗癌疗法的发展历程,重点介绍了顺铂、铂(IV)原药以及光动力疗法(PDT)的发展,以提高癌症治疗效果。综述的第一部分深入探讨了顺铂成功的历史背景和分子机制,强调了它的DNA结合特性以及随后对细胞过程的干扰。尽管顺铂具有临床疗效,但其固有的局限性,包括剂量依赖性毒性和获得性抗药性,加速了对新型铂衍生物的探索。这导致了铂(IV)原药的出现,旨在通过靶向给药克服耐药性机制并提高选择性。下文将深入分析铂(IV)原药开发过程中采用的设计原则和结构改造。光动力疗法(PDT)的过渡是铂类抗癌疗法的一种协同方法。本文结合铂络合物在光动力疗法中的潜在应用,讨论了铂络合物的光物理特性,强调了铂类药物的细胞毒性效应和光诱导的活性氧生成。这种双重作用的方法有望克服传统化疗的局限性,并产生卓越的治疗效果。总之,本报告探讨了铂复合物开发和使用的最新进展,重点介绍了联合治疗、靶向给药方法和多功能复合物的生成等新策略。报告还全面概述了当前的形势,同时提出了下一代铂类抗癌疗法的未来发展方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Advancements in platinum-based anticancer drug development: A comprehensive review of strategies, discoveries, and future perspectives

Platinum-based anticancer drugs have been at the forefront of cancer chemotherapy, with cisplatin emerging as a pioneer in the treatment of various malignancies. This review article provides a comprehensive overview of the evolution of platinum-based anticancer therapeutics, focusing on the development of cisplatin, platinum(IV) prodrugs, and the integration of photodynamic therapy (PDT) for enhanced cancer treatment results. The first section of the review delves into the historical context and molecular mechanisms underlying the success of cisplatin, highlighting its DNA binding properties and subsequent interference with cellular processes. Despite its clinical efficacy, the inherent limitations, including dose-dependent toxicities and acquired resistance, accelerated the exploration of novel platinum derivatives. This led to the emergence of platinum(IV) prodrugs, designed to overcome resistance mechanisms and enhance selectivity through targeted drug delivery. The subsequent section provides an in-depth analysis of the principles of design and structural modifications employed in the development of platinum(IV) prodrugs. The transitions to the incorporation of photodynamic therapy (PDT) stands out as a synergistic approach to platinum-based anticancer treatment. The photophysical properties of platinum complexes are discussed in the context of their potential application in PDT, emphasizing on combined cytotoxic effects of platinum-based drugs and light-induced reactive oxygen species generation. This dual-action approach holds great promise for overcoming the limitations of traditional chemotherapy as well as producing superior therapeutic outcomes. Overall, the present report explores the latest developments in the development and use of platinum complexes, highlighting novel strategies such combination treatments, targeted delivery methods, and the generation of multifunctional complexes. It also provides a comprehensive overview of the current landscape while proposing future directions for the development of next-generation platinum-based anticancer therapeutics.

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来源期刊
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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