{"title":"DNA or Not DNA —That is the Question Determining the Design of Platinum Anticancer Drugs","authors":"Suxing Jin, Chenyao Feng, Xiaoyong Wang","doi":"10.1016/j.ejmech.2024.117077","DOIUrl":null,"url":null,"abstract":"Platinum drugs are the most widely used chemotherapeutics to treat various tumors. Their primary mode of action is supposed to be inducing apoptosis of cancer cells via covalent binding to DNA. This mechanism has shackled the design of new platinum drugs for many years. Mounting evidence shows that many platinum complexes form non-covalent adducts with DNA or interact with proteins to exhibit significant antitumor activity, thus implying some distinct mechanisms from that of traditional platinum drugs. These unconventional examples indicate that covalent DNA binding is not the precondition for the antitumor activity of platinum complexes, and diversified reactions or interactions with biomolecules, organelles, signal pathways, or immune system could lead to the antitumor activity of platinum complexes. The atypical mechanisms break the classical DNA-only paradigm and structure−activity relationships, thus opening a wide avenue for the design of innovative platinum anticancer drugs.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"76 1","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejmech.2024.117077","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Platinum drugs are the most widely used chemotherapeutics to treat various tumors. Their primary mode of action is supposed to be inducing apoptosis of cancer cells via covalent binding to DNA. This mechanism has shackled the design of new platinum drugs for many years. Mounting evidence shows that many platinum complexes form non-covalent adducts with DNA or interact with proteins to exhibit significant antitumor activity, thus implying some distinct mechanisms from that of traditional platinum drugs. These unconventional examples indicate that covalent DNA binding is not the precondition for the antitumor activity of platinum complexes, and diversified reactions or interactions with biomolecules, organelles, signal pathways, or immune system could lead to the antitumor activity of platinum complexes. The atypical mechanisms break the classical DNA-only paradigm and structure−activity relationships, thus opening a wide avenue for the design of innovative platinum anticancer drugs.
铂类药物是治疗各种肿瘤最广泛使用的化疗药物。它们的主要作用方式是通过与 DNA 的共价结合诱导癌细胞凋亡。这种机制多年来一直束缚着新铂类药物的设计。越来越多的证据表明，许多铂复合物与 DNA 形成非共价加合物，或与蛋白质相互作用，从而表现出显著的抗肿瘤活性，这意味着与传统铂类药物的机制不同。这些非传统的例子表明，DNA共价结合并不是铂复合物抗肿瘤活性的前提条件，与生物大分子、细胞器、信号通路或免疫系统的多样化反应或相互作用可能导致铂复合物的抗肿瘤活性。非典型机制打破了经典的纯 DNA 范式和结构-活性关系，从而为设计创新的铂类抗癌药物开辟了一条广阔的道路。
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.
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