Current medicinal chemistry. Anti-cancer agents最新文献_第2页

Recent advances in understanding and exploiting the activation of anthracyclines by formaldehyde. 甲醛活化蒽环类药物的研究进展。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866964

S M Cutts, L P Swift, A Rephaeli, A Nudelman, D R Phillips

{"title":"Recent advances in understanding and exploiting the activation of anthracyclines by formaldehyde.","authors":"S M Cutts, L P Swift, A Rephaeli, A Nudelman, D R Phillips","doi":"10.2174/1568011054866964","DOIUrl":"https://doi.org/10.2174/1568011054866964","url":null,"abstract":"The anthracycline group of compounds are amongst the most effective chemotherapy agents currently in use for cancer treatment. They are generally classified as topoisomerase II inhibitors but also have a variety of other targets in cells. It has been known for some years that the anthracyclines are capable of forming DNA adducts, but the relevance and extent of these DNA adducts in cells and their role in causing cell death has remained obscure. When the adduct structure was solved, it became clear that formaldehyde was an absolute requirement for adduct formation. This led to a renewed interest in the capacity of anthracyclines to form DNA adducts, and there are now several ways in which adduct formation can be facilitated in cells. These involve strategies to provide the requisite formaldehyde in the form of anthracycline-formaldehyde conjugates, and the use of formaldehyde-releasing drugs in combination with anthracyclines. Of particular interest is the new therapeutic compound AN-9 that releases both butyric acid and formaldehyde, leading to efficient anthracycline-DNA adduct formation, and synergy between the two compounds. Targeted formation of adducts using anthracycline-formaldehyde conjugates tethered to cell surface targeted molecules is now also possible. Some of the cellular consequences of these adducts have now been studied, and it appears that their formation can overcome anthracycline-resistance mechanisms, and that they are more efficient at inducing apoptosis than when functioning primarily through impairment of topoisomerase II. The clinical application of the use of anthracyclines as DNA adduct forming agents is now being explored.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 5","pages":"431-47"},"PeriodicalIF":0.0,"publicationDate":"2005-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054866964","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25599999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

An analysis of the binding modes of ATP-competitive CDK2 inhibitors as revealed by X-ray structures of protein-inhibitor complexes. 蛋白质-抑制剂复合物的x射线结构揭示了atp竞争性CDK2抑制剂的结合模式分析。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866928

Anna Vulpetti, Paolo Pevarello

引用次数: 18

Blocking the PI3K/PKB pathway in tumor cells. 阻断肿瘤细胞中PI3K/PKB通路。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866937

Frédéric Stauffer, Philipp Holzer, Carlos García-Echeverría

引用次数: 38

Steroid sulfatase inhibitors: their potential in the therapy of breast cancer. 类固醇硫酸酯酶抑制剂:它们在乳腺癌治疗中的潜力。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866955

Peter Nussbaumer, Andreas Billich

{"title":"Steroid sulfatase inhibitors: their potential in the therapy of breast cancer.","authors":"Peter Nussbaumer, Andreas Billich","doi":"10.2174/1568011054866955","DOIUrl":"https://doi.org/10.2174/1568011054866955","url":null,"abstract":"Steroid sulfatase (STS) is the only well characterized enzyme in human cells that is capable to desulfate estrone 3-sulfate (E1S) and dehydroepiandrosterone sulfate (DHEAS) as a first step in the conversion of these precursors to active hormones. STS has been found to be highly expressed in estrogen-dependent breast tumors in post-menopausal women and is regarded as a crucial component of the local estrogen production that is required for tumor growth and survival. Inhibitors of STS are expected to block the intra-tumoral estrogen synthesis and, therefore, are considered as potential new therapeutic agents for the treatment of estrogen-dependent cancers of the breast and the endometrium. In this review, we give an overview on the current status in the field of medicinal chemistry of STS inhibitors. Newer developments comprise potent aryl sulfamate-based irreversible inhibitors, and several types of reversible inhibitors. Other directions include compounds with dual mode of action, such as compounds that block both STS and aromatase, or act as STS inhibitors and antiproliferative or antiangiogenic agents at the same time. In particular, these agents featuring an extended mode of action hold promise to be included in the armamentarium to fight endocrine-dependent cancer.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 5","pages":"507-28"},"PeriodicalIF":0.0,"publicationDate":"2005-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054866955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25600004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Programmable DNA binding oligomers for control of transcription. 控制转录的可编程DNA结合低聚物。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222346

Peter B Dervan, Raymond M Doss, Michael A Marques

引用次数: 119

Etoposide, topoisomerase II and cancer. 依托泊苷，拓扑异构酶II与癌症。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222364

E L Baldwin, N Osheroff

{"title":"Etoposide, topoisomerase II and cancer.","authors":"E L Baldwin, N Osheroff","doi":"10.2174/1568011054222364","DOIUrl":"https://doi.org/10.2174/1568011054222364","url":null,"abstract":"Etoposide is an important chemotherapeutic agent that is used to treat a wide spectrum of human cancers. It has been in clinical use for more than two decades and remains one of the most highly prescribed anticancer drugs in the world. The primary cytotoxic target for etoposide is topoisomerase II. This ubiquitous enzyme regulates DNA under- and overwinding, and removes knots and tangles from the genome by generating transient double-stranded breaks in the double helix. Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known as the cleavage complex) that is a transient intermediate in the catalytic cycle of topoisomerase II. The accumulation of cleavage complexes in treated cells leads to the generation of permanent DNA strand breaks, which trigger recombination/repair pathways, mutagenesis, and chromosomal translocations. If these breaks overwhelm the cell, they can initiate death pathways. Thus, etoposide converts topoisomerase II from an essential enzyme to a potent cellular toxin that fragments the genome. Although the topoisomerase II-DNA cleavage complex is an important target for cancer chemotherapy, there also is evidence that topoisomerase II-mediated DNA strand breaks induced by etoposide and other agents can trigger chromosomal translocations that lead to specific types of leukemia. Given the central role of topoisomerase II in both the cure and initiation of human cancers, it is imperative to further understand the mechanism by which the enzyme cleaves and rejoins the double helix and the process by which etoposide and other anticancer drugs alter topoisomerase II function.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 4","pages":"363-72"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054222364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 462

Competition dialysis: an assay to measure the structural selectivity of drug-nucleic acid interactions. 竞争透析:一种测定药物-核酸相互作用结构选择性的方法。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222292

Jonathan B Chaires

{"title":"Competition dialysis: an assay to measure the structural selectivity of drug-nucleic acid interactions.","authors":"Jonathan B Chaires","doi":"10.2174/1568011054222292","DOIUrl":"https://doi.org/10.2174/1568011054222292","url":null,"abstract":"Competition dialysis is a powerful new tool for the discovery of ligands that bind to nucleic acids with structural- or sequence-selectivity. The method is based on firm thermodynamic principles and is simple to implement. In the competition dialysis experiment, an array of nucleic acid structures and sequences is dialyzed against a common test ligand solution. After equilibration, the amount of ligand bound to each structure or sequence is determined spectrophotometrically. Since all structures and sequences are in equilibrium with the same free ligand concentration, the amount bound is directly proportional to the ligand binding affinity. Competition dialysis thus provides a direct and quantitative measure of selectivity, and unambiguously identifies which of the structures or sequences within the sample array that are preferred by a particular ligand. Following the introduction of the method, competition dialysis has been used worldwide to probe a variety of ligand-nucleic acid interactions. This contribution will focus on new analytical approaches for extracting information from the database that resulted from the first-generation competition dialysis assay, in which binding data was gathered for the interaction of 126 compounds with 13 different structures and sequences. Such global analyses allow identification of compounds with unique types of binding selectivity.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 4","pages":"339-52"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054222292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 49

Camptothecin: roles of the D and E rings in binding to the topoisomerase I-DNA covalent binary complex. 喜树碱:D环和E环在结合拓扑异构酶I-DNA共价二元复合物中的作用。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222373

Sidney M Hecht

引用次数: 13

Triplex-forming oligonucleotides as potential tools for modulation of gene expression. 三聚体形成寡核苷酸作为调控基因表达的潜在工具。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222300

Faye A Rogers, Janice A Lloyd, Peter M Glazer

{"title":"Triplex-forming oligonucleotides as potential tools for modulation of gene expression.","authors":"Faye A Rogers, Janice A Lloyd, Peter M Glazer","doi":"10.2174/1568011054222300","DOIUrl":"https://doi.org/10.2174/1568011054222300","url":null,"abstract":"Triplex-forming oligonucleotides (TFOs) bind in the major groove of duplex DNA at polypurine/ polypyrimidine stretches in a sequence-specific manner. The binding specificity of TFOs makes them potential candidates for use in directed genome modification. A number of studies have shown that TFOs can introduce permanent changes in a target sequence by stimulating a cell's inherent repair pathways. TFOs have also been demonstrated to inhibit gene expression providing a possible role for these compounds in cancer therapy. This review summarizes the dual roles of TFOs for use in delivering DNA reactive compounds to a specific site in the genome or for introducing permanent changes in the target sequence through the introduction of an altered helical structure. In addition to compiling the ways in which TFOs have been successfully utilized, this review will explore conflicting reports of TFO bioactivity focusing on the variables which affect the efficacy in vitro of TFO mediated genomic modification which in turn may represent the obstacles encountered using TFOs to modulate gene expression in vivo.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 4","pages":"319-26"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054222300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 56

Recognition of triple helical nucleic acids by aminoglycosides. 氨基糖苷对三螺旋核酸的识别。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-07-01 DOI: 10.2174/1568011054222328

H Xi, D P Arya

{"title":"Recognition of triple helical nucleic acids by aminoglycosides.","authors":"H Xi, D P Arya","doi":"10.2174/1568011054222328","DOIUrl":"https://doi.org/10.2174/1568011054222328","url":null,"abstract":"Aminoglycosides, traditional RNA binders, were found to be a new class of triple helical nucleic acid-stabilizing ligands. Neomycin, of all the aminoglycosides, has shown the most significant effects in stabilizing DNA, RNA, and hybrid triple helices. When compared with minor groove binders or intercalators, neomycin excels at triple helical stabilization in most cases. Molecular modeling studies suggest that neomycin reaches into the larger Watson-Hoogsteen groove. The charge and shape complementarity are the key factors in neomycin-triplex recognition. By conjugating neomycin with intercalators such as BQQ (a potent triple helix intercalating agent designed by Hélène), we have progressed in developing more potent triple helix stabilizing ligands. The design of such dual or even triple recognition ligands opens a new paradigm for recognition of triple helix nucleic acids. The article herein presents studies of neomycin as the first molecule that can selectively stabilize nucleic acid triplex structures. These studies are supported by our recent discovery that neomycin prefers to bind to A-like conformations, of which triple helix structures are known to display some characteristics. These findings will contribute to the development of a new series of triplex-specific ligands, and may contribute to either antisense or antigene therapies.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 4","pages":"327-38"},"PeriodicalIF":0.0,"publicationDate":"2005-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054222328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17