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

[Display omitted] •Platinum-based anticancer drugs induce apoptosis by forming platinum-DNA adducts.•These drugs exhibit significant efficacy in treating testicular, ovarian, colorectal, lung, and bladder cancers.•Resistance via enhanced DNA repair, drug efflux, and glutathione inactivation, causing...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2024-10, Vol.112, p.117894, Article 117894
Hauptverfasser: Sahoo, Debsankar, Deb, Priya, Basu, Tamal, Bardhan, Srishti, Patra, Sayan, Sukul, Pradip K.
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Sprache:eng
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Zusammenfassung:[Display omitted] •Platinum-based anticancer drugs induce apoptosis by forming platinum-DNA adducts.•These drugs exhibit significant efficacy in treating testicular, ovarian, colorectal, lung, and bladder cancers.•Resistance via enhanced DNA repair, drug efflux, and glutathione inactivation, causing toxicity issues.•The emergence of other metal complexes as anticancer drugs: A competitive and cooperative landscape with platinum-based therapies.•Ongoing development of platinum compounds focuses on targeted delivery, combined therapies, prodrugs, and phototherapy. 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. I
ISSN:0968-0896
1464-3391
1464-3391
DOI:10.1016/j.bmc.2024.117894