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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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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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类肽作为天然活性肽的结构或功能模拟物,具有3个优点:一是能够保留天然肽的底物功能,二是可改善其代谢性质,三是可提高其作用的靶向专一性等特点.高活性的类肽分子设计可通过构象限定、结构改造和非肽模拟物设计的构思等多种手段实现.目前肿瘤化疗药物开发的研究热点已由细胞毒药物转向靶向治疗药物,在肿瘤发生发展过程中起关键作用的许多蛋白酶和肽酶陆续被发现,因此类肽作为潜在的肿瘤化疗药物已倍受关注,而如何设计具有抗肿瘤活性的小分子类肽酶抑制剂则已成为研究的热点.本课题组多年来一直致力于研究开发APN、MMPs及HDACs的小分子类肽抑制剂作为靶向抗肿瘤药物先导物.这三种锌离子依赖性金属蛋白酶在肿瘤的生长侵袭转移、血管生成和基质降解等发展进程中起着关键作用,靶向于该类生物靶点的小分子类肽抑制剂具有开发成为高选择性抗肿瘤药物的巨大潜力. 相似文献
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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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Valentina Boscaro Alessandro Barge Annamaria Deagostino Elena Ghibaudi Enzo Laurenti Domenica Marabello Eliano Diana Margherita Gallicchio 《Molecules (Basel, Switzerland)》2021,26(18)
Vanadium has a good therapeutic potential, as several biological effects, but few side effects, have been demonstrated. Evidence suggests that vanadium compounds could represent a new class of non-platinum, metal antitumor agents. In the present study, we aimed to characterize the antiproliferative activities of fluorescent vanadyl complexes with acetylacetonate derivates bearing asymmetric substitutions on the β-dicarbonyl moiety on different cell lines. The effects of fluorescent vanadyl complexes on proliferation and cell cycle modulation in different cell lines were detected by ATP content using the CellTiter-Glo Luminescent Assay and flow cytometry, respectively. Western blotting was performed to assess the modulation of mitogen-activated protein kinases (MAPKs) and relevant proteins. Confocal microscopy revealed that complexes were mainly localized in the cytoplasm, with a diffuse distribution, as in podocyte or a more aggregate conformation, as in the other cell lines. The effects of complexes on cell cycle were studied by cytofluorimetry and Western blot analysis, suggesting that the inhibition of proliferation could be correlated with a block in the G2/M phase of cell cycle and an increase in cdc2 phosphorylation. Complexes modulated mitogen-activated protein kinases (MAPKs) activation in a cell-dependent manner, but MAPK modulation can only partly explain the antiproliferative activity of these complexes. All together our results demonstrate that antiproliferative effects mediated by these compounds are cell type-dependent and involve the cdc2 and MAPKs pathway. 相似文献
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A new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel 9-anilino-2,3-ethylenedioxyacridines (five compounds) have been synthesized and evaluated for activity against P388 leukemia in vivo. A few of them possessed the same potency of antitumor activity as amsacrine (m-AMSA) which is an important antitumor agent in clinical use. 相似文献
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Jiatong Li Ao Gu Xiao-Mei Nong Shuyang Zhai Zhu-Ying Yue Meng-Yao Li Prof. Yingbin Liu 《Chemical record (New York, N.Y.)》2023,23(12):e202300293
Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity to explore and investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form a highly significant category of antitumor agents. Among these, antitumor agents with six-membered aromatic nitrogen heterocycles have consistently attracted the attention of chemists and pharmacologists. Accordingly, we present a comprehensive summary of synthetic strategies and clinical implications of these compounds in this review. This entails an in-depth analysis of synthesis pathways for pyridine, quinoline, pyrimidine, and quinazoline. Additionally, we explore the historical progression, targets, mechanisms of action, and clinical effectiveness of small molecule inhibitors possessing these structural features. 相似文献
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Synthesis and DNA binding of spirocyclic model compounds related to the neocarzinostatin chromophore
[formula: see text] Spirocyclic model compounds which mimic the molecular architecture of one of the decomposition products of the antitumor agent NCS-chrom have been synthesized. These readily accessible molecules bind with remarkable efficiency to bulged DNA oligonucleotides, offering potential for the design of therapeutic agents. 相似文献
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Our research improves the structure diversity of naphthalimide antitumor agents and distinct variances of antitumor targets and mechanism of action. 相似文献
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In the biological and physical investigation of a new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel 9-anilino-2,3-methylenedioxyacridines (twelve compounds) have been synthesized and evaluated for the activity against L1210 leukemia in vivo. A few of them possessed the same potency of the antitumor activity as 4′-(9-acridinylamino)methanesulfonyl-m-anisidine (amsacrine, m-AMSA), which is an important antitumor agent in clinical use. The molecular structure of a typical one, 9a in this series have been determined by the X-ray diffraction method using a single crystal. The results of this X-ray investigation have shown that the new class of acridine derivatives have the methylenedioxy group fused at the 2- and 3-positions of the acridine ring. 相似文献
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The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties. 相似文献
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IntroductionOrganotin compounds have attracted attentionas an optimal model for antitumour agents due tothe function of the interesting intramolecularO→Sn coordination[1,2 ] . Our recent concern hasbeen focused on the preparation of ( Z) - 1 - [2 -( triarylstannyl) vinyl]- cyclooctanol[3 ] .In order tofind more appropriate compounds used asanticancer agents and explore the effect of thecoordinate O→ Sn interaction to the antitumoractivity,the new compounds werehalodemetallated and characte… 相似文献