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金属药物有许多其它药物无法比拟的独特性质,以顺铂为代表的铂类抗癌药物在癌症临床化疗中发挥了巨大作用。但是铂类药物的毒副作用严重限制了它们的实际疗效和适用范围,因此需要继续研究具有不同作用机理的新型金属抗癌药物,以改良或补充现有铂类药物的性能。本文重点介绍了近年来设计金属抗癌药物的一些新策略,包括改变铂类药物与DNA的作用模式、改进铂类药物对肿瘤的靶向性、研发非铂类金属抗癌药物和寻找DNA以外的作用靶标等。这些内容体现了该领域的最新发展趋势,为从事金属抗癌药物开发研究的科技人员提供了有益的参考信息。 相似文献
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自1978年顺铂成功地被开发成癌症临床治疗药物以来,金属配合物作为小分子抗癌药物的开发成为人们的研究热点。其中,氮杂环卡宾能与多种过渡金属中心形成稳定的共价键,这种特殊的稳定性使得金属氮杂环卡宾配合物具有被开发成药物的潜能。近年来,金属氮杂环卡宾配合物被发现具有良好的抗癌活性,激发了广大无机药物化学研究者的研究热情。综合笔者课题组在金属氮杂环卡宾抗肿瘤配合物方面的前期研究,本文将对银、金、铑和铂氮杂环卡宾配合物的抗肿瘤活性及作用机制进行综述,以期为新型金属氮杂环卡宾抗肿瘤化合物的设计合成提供参考。 相似文献
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肿瘤化学免疫治疗是免疫疗法与化学疗法相结合通过协同作用治疗肿瘤的一种新方法。以铂类药物为代表的金属药物是一类重要的化学抗肿瘤药物,其作用机理是与肿瘤细胞DNA形成交联物并阻止其复制;但是,这类药物存在严重的毒性和耐药性问题。近年来发现有些金属配合物在产生细胞毒性的同时,也通过多种机制参与机体的免疫调节过程,其中以诱导免疫原性细胞死亡(ICD)最为常见。本文简要介绍了肿瘤化学免疫治疗的基本概念以及与免疫抑制有关的肿瘤微环境,概述了金属配合物的免疫活性和调节免疫过程的基本原理,并以铂类药物为例总结了金属配合物调节免疫过程的可能途径,最后列举了若干具有ICD诱导潜力和其他免疫调节功能的非铂类金属配合物,指出了目前化学免疫治疗存在的问题和未来的应用潜力。化学治疗与免疫治疗结合既可以利用机体免疫系统增强金属配合物的抗肿瘤效果,又可以减少药物剂量,降低毒副作用,是设计金属抗肿瘤药物的新方向之一。 相似文献
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紫苏醇作为既有癌症预防又有癌症治疗作用的少数几种天然产物之一,曾作为临床药物用于癌症的治疗。但是紫苏醇通过口服给药生物利用度低、给药剂量大,因而限制了它的临床应用。我们将紫苏醇进行化学修饰,作为配体引入到芳基金属配合物中,合成了一种新型芳基钌配合物Ru-L,并利用核磁共振氢谱、碳谱、电喷雾质谱及元素分析对其进行了基础表征。配合物Ru-L对肿瘤细胞A2780、A2780/DDP及MCF-7都表现出较高的细胞毒活性,而对正常细胞株毒性较小(IC_(50)200μmol·L~(-1)),表明紫苏醇芳基钌配合物可以克服紫苏醇给药量大和毒性大等缺陷。紫外可见及荧光光谱表明配合物具有较快的水解速率,可通过嵌入作用与CT-DNA结合,并通过静态猝灭与BSA/HSA相互作用。流式细胞术也揭示配合物将肿瘤细胞周期阻滞在G0/G1期,从而导致了肿瘤细胞的凋亡。以上结果表明,基于紫苏醇的芳基钌配合物Ru-L克服了紫苏醇的高剂量、高毒性等缺点。 相似文献
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二十世纪七十年代,顺铂作为抗肿瘤药物在临床上的广泛使用,使无机过渡金属配合物的抗肿瘤活性成为生物医药领域的研究热点之一;随后研究者在数千个铂系金属配合物中又筛选出了毒性相对较低的广谱抗肿瘤药物卡铂和环硫铂[1].但是临床上化疗药物的疗效、毒副作用和肿瘤细胞的耐药性等问题仍是生物医药领域亟待解决的关键问题之一.钌和钌配合物在生物体内易于吸收和代谢,属于低毒性的化合物;而且钌配合物具有与铂配合物相似的分子结构,能够以插入方式、沟结合方式和静电作用方式与DNA分子交联,干扰核酸的生物功能.国际上已普遍认为,钌配合物将成为最有前途的抗肿瘤药物之一[2]. 相似文献
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从构效关系看铂配合物的抗癌作用 总被引:1,自引:0,他引:1
本世纪60年代末期,Barnett Rosenberg与其合作者发现了顺铂(cis-[PtCl_2(NH_3)_2]的抗癌活性.至今,顺铂作为一种有效的抗癌药物虽已广泛运用于临床,但它有严重的肾毒性和胃肠道反应,引起高音失听等副作用.同时顺铂水溶性低,水溶液不够稳定,缓解期短.为此,人们对铂配合物的抗癌活性与配合物结构关系以及配合物中各个配位基团对活性的影响进行了研究.企望能从具有抗癌活性的铂配合物中,筛选出高效、低毒、水溶性高、稳定性好的抗癌药物. 相似文献
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1,10-菲咯啉及其衍生物铜配合物的抗癌活性研究进展 总被引:1,自引:0,他引:1
作为一种微量生命元素,铜在生物进程中扮演着重要角色,很多铜配合物呈现抑制癌细胞增殖的活性。本文论述了以1,10-菲咯啉及其衍生物为配体的铜配合物的抗癌活性研究进展,分析了其对DNA裂解的可能机理。对比顺铂类抗癌药物,展望了铜配合物作为抗癌药物的应用前景。 相似文献
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20世纪60年代,美国密执安州立大学Rosenberg发现了顺铂具有抗癌活性,开辟了金属类抗肿瘤药物研究的新领域.经过40余年的研究,已相继成功开发了卡铂、奈达铂、奥沙利铂、舒铂、洛铂和双环铂等铂类抗肿瘤药物.虽然对于铂类抗肿瘤药物研究取得了一定的成绩,但在临床使用过程中也存在一些问题,如其毒副作用和抗药性,限制了其在临床上的进一步广泛应用.为了解决这些问题,科研工作者开始寻找新的金属类抗肿瘤药物以弥补现有铂类抗肿瘤药物的不足.在金属元素中,唯有钯(II)与铂(II)配合物具有相似或相同的结构特征,进而表现出相近或相似的化学性质.因此,继铂类抗肿瘤配合物后,钯(II)配合物作为潜在抗肿瘤药物成为一个诱人的领域.本文综述了近年来钯(II)类抗肿瘤药物的研究进展,并探讨了其构效关系,这对于指导新型钯(II)类抗肿瘤药物的合成具有重要的参考价值. 相似文献
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Alexander Kastner Isabella Poetsch Josef Mayr Jaroslav V. Burda Alexander Roller Petra Heffeter Bernhard K. Keppler Christian R. Kowol 《Angewandte Chemie (International ed. in English)》2019,58(22):7464-7469
Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, PtIV complexes are considered to define the future of anticancer platinum drugs. The aqueous stability of a series of biscarboxylato PtIV complexes was studied under physiologically relevant conditions. Unexpectedly and in contrast to the current chemical understanding, especially oxaliplatin and satraplatin complexes underwent fast hydrolysis in equatorial position (even in cell culture medium and serum). Notably, the resulting hydrolysis products strongly differ in their reduction kinetics, a crucial parameter for the activation of PtIV drugs, which also changes the anticancer potential of the compounds in cell culture. The discovery that intact PtIV complexes can hydrolyze at equatorial position contradicts the dogma on the general kinetic inertness of PtIV compounds and needs to be considered in the screening and design for novel platinum‐based anticancer drugs. 相似文献
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Although classical platinum drugs such as cisplatin, carboplatin and oxaliplatin play a vitally important role in cancer treatment, nonselective distribution of platinum drugs in normal and tumor cells can induce serious gastrointestinal reaction, nephrotoxicity, ototoxicity, neurotoxicity and cross resistance, limiting their applications. Over the past few years, a great number of platinum complexes of non‐classical structures have been extensively investigated and evaluated in vitro and in vivo, some of them exhibiting considerable activity. In this review, platinum‐based complexes with non‐classical structures which have anticancer potential are described and several representative examples are discussed with their mechanism of action. 相似文献
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Targeting platinum anti-tumour drugs: Overview of strategies employed to reduce systemic toxicity 总被引:1,自引:0,他引:1
Steven van Zutphen 《Coordination chemistry reviews》2005,249(24):2845-2853
Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity of chemotherapy, in particular, platinum-based chemotherapy. Finding successful strategies for the targeting of platinum anticancer drugs has therefore been a subject of extensive research. This review paper gives an overview of some of the different approaches that have recently been used in the development of targeted platinum anticancer drugs. 相似文献
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Platinum-based anticancer drugs, including cisplatin and its analogues, have played important roles in the clinical treatment of solid tumors over the past 38 years. However, poor selectivity, high toxicity and intrinsic or acquired drug resistance profoundly limit their application, which encourages the development of novel transition metal-based anticancer agents with different mechanisms of action. To this end, transition metal complexes that can simultaneously act on more than one target, termed as single-molecule multi-targeting complexes, have attracted increasing attention because of their enhanced efficacy and diminished chance of drug resistance. In this review, we systematically discuss the recent progress in the development of platinum- and ruthenium-based anticancer agents, in particular the rational design of platinum and ruthenium complexes with multi-targeting features. 相似文献
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There are abundant sources of anticancer drugs in nature that have a broad prospect in anticancer drug discovery. Natural compounds, with biological activities extracted from plants and marine and microbial metabolites, have significant antitumor effects, but their mechanisms are various. In addition to providing energy to cells, mitochondria are involved in processes, such as cell differentiation, cell signaling, and cell apoptosis, and they have the ability to regulate cell growth and cell cycle. Summing up recent data on how natural products regulate mitochondria is valuable for the development of anticancer drugs. This review focuses on natural products that have shown antitumor effects via regulating mitochondria. The search was done in PubMed, Web of Science, and Google Scholar databases, over a 5-year period, between 2015 and 2020, with a keyword search that focused on natural products, natural compounds, phytomedicine, Chinese medicine, antitumor, and mitochondria. Many natural products have been studied to have antitumor effects on different cells and can be further processed into useful drugs to treat cancer. In the process of searching for valuable new drugs, natural products such as terpenoids, flavonoids, saponins, alkaloids, coumarins, and quinones cover the broad space. 相似文献
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超分子抗癌药物双环铂的结构研究 总被引:1,自引:0,他引:1
铂类抗癌药物在水中的溶解度和稳定性直接与药物的活性和毒性有关.几十年来,为了改进药物的效能和降低药物的毒性,做了大量的研究.超分子铂类化合物可能具有与众不同的物理化学性质,我们成功设计和合成了一个新型的超分子抗癌药物-双环铂,己证实双环铂对人类的恶性肿瘤有好的治疗效果.用X射线单晶衍射法测定了双环铂的晶体结构,又用电喷雾离子化质谱研究了它在水溶液中的状态.根据实验结果提出了双环铂在水溶液中的结构模型,解释了双环铂在水中好的稳定性和溶解度. 相似文献
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DAI Qianhuan . Center of Chemistry Bioengineering of Cancer Research Beijing Polytechnic University 《中国科学B辑(英文版)》2006,49(1):44-62
Historically,leading anticancer agents have all been discovered by fortuitous events,and advances in the new anticancer agent proceed from random screening of a large quantity of the leading anticancer drug con-geners and individual and specific natural p… 相似文献