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Current medicinal chemistry. Anti-cancer agents最新文献

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Biological targets of antitumor indolocarbazoles bearing a sugar moiety. 含糖部分的抗肿瘤吲哚咔唑的生物学靶点。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-11-01 DOI: 10.2174/1568011043352650
Michelle Prudhomme
{"title":"Biological targets of antitumor indolocarbazoles bearing a sugar moiety.","authors":"Michelle Prudhomme","doi":"10.2174/1568011043352650","DOIUrl":"https://doi.org/10.2174/1568011043352650","url":null,"abstract":"<p><p>Natural and synthetic indolocarbazole compounds have triggered considerable interest since the discovery in 1986 of the inhibitory properties of staurosporine toward protein kinase C (PKC). Later, it has been shown that indolocarbazole compounds may inhibit various kinases, such as cyclin dependent-kinases and/or topoisomerase I, someones behave only as DNA intercalators. In this review are presented various indolocarbazole compounds bearing a sugar moiety and their biological targets. The relevance of these targets to develop indolocarbazole compounds as potential antitumor agents is discussed.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 6","pages":"509-21"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011043352650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844685","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: 58
Role of the non-neuronal human cholinergic system in lung cancer and mesothelioma: possibility of new therapeutic strategies. 非神经元人类胆碱能系统在肺癌和间皮瘤中的作用:新的治疗策略的可能性。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-11-01 DOI: 10.2174/1568011043352687
Sonya Trombino, Alessandra Bisio, Alessia Catassi, Alfredo Cesario, Carla Falugi, Patrizia Russo
{"title":"Role of the non-neuronal human cholinergic system in lung cancer and mesothelioma: possibility of new therapeutic strategies.","authors":"Sonya Trombino,&nbsp;Alessandra Bisio,&nbsp;Alessia Catassi,&nbsp;Alfredo Cesario,&nbsp;Carla Falugi,&nbsp;Patrizia Russo","doi":"10.2174/1568011043352687","DOIUrl":"https://doi.org/10.2174/1568011043352687","url":null,"abstract":"<p><p>Acetylcholine (Ach), one of the most important examples of a neurotransmitter, represents a phylogenetically old molecule, widely distributed from bacteria to humans. The finding that neuronal Ach receptors (nAChRs) are present in non-neuronal cells raised some interesting issues related to their specific activity. In humans, different studies have showed that many lung cancer cells expressed nAchRs and that low concentrations of nicotine blocked the induction of apoptosis in these cells. A recent study presents data that SCLC express a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phenotype and that ACh exerts as an autocrine growth factor in human lung tumors. Recently it has been shown that human malignant pleural mesothelioma express a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cell growth as well as normal mesothelial cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) has a proliferative effect and antagonists (i.e. curare) has an inhibitory effect. Furthermore apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-kappaB complexes and phosphorilation of Bad at Serine(112), curare proapoptotic via G(0)-G(1) arrest p21(waf-1)-dependent, but p53-independent). The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and open up new therapeutic strategies.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 6","pages":"535-42"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011043352687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24842897","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: 30
Multiple targeting by the antitumor drug tamoxifen: a structure-activity study. 抗肿瘤药物他莫昔芬的多重靶向:结构-活性研究。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-11-01 DOI: 10.2174/1568011043352696
Philippe de Médina, Gilles Favre, Marc Poirot
{"title":"Multiple targeting by the antitumor drug tamoxifen: a structure-activity study.","authors":"Philippe de Médina,&nbsp;Gilles Favre,&nbsp;Marc Poirot","doi":"10.2174/1568011043352696","DOIUrl":"https://doi.org/10.2174/1568011043352696","url":null,"abstract":"<p><p>Tamoxifen is a well-known antiestrogen used for the hormonotherapy of estrogen receptor positive breast cancer. In addition to its high affinity binding to the estrogen receptor (ER), tamoxifen binds with comparable affinity to the microsomal antiestrogen binding site (AEBS), and inhibits with a micromolar efficiency, protein kinase C (PKC), calmodulin (CaM)-dependent enzymes and Acyl CoenzymeA: Cholesterol Acyl Transferase (ACAT). Each of these tamoxifen targets might explain the genomic as well as non-genomic effects of tamoxifen. In this review, we will report current knowledge about the structural features of tamoxifen involved in this multiple targeting. These data provide a useful guide for the conception of selective ligands of ERs, AEBS, PKC, CaM or ACAT based on the chemical structure of tamoxifen.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 6","pages":"491-508"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011043352696","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844684","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: 75
Cytoprotection and immunomodulation in cancer therapy. 肿瘤治疗中的细胞保护和免疫调节。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-11-01 DOI: 10.2174/1568011043352704
Sham Diwanay, Manish Gautam, Bhushan Patwardhan
{"title":"Cytoprotection and immunomodulation in cancer therapy.","authors":"Sham Diwanay,&nbsp;Manish Gautam,&nbsp;Bhushan Patwardhan","doi":"10.2174/1568011043352704","DOIUrl":"https://doi.org/10.2174/1568011043352704","url":null,"abstract":"<p><p>Bioprospecting and natural products drug development for cancer treatment has become an important area. Most of the cancer chemotherapeutic agents are associated with toxicity towards normal cells and tissues. Optimal dosing of cancer chemotherapeutic agents is often limited because of severe non-myelosuppressive and myelosuppressive toxicities. It is a continuing challenge to design therapy that is safer, effective and selective. Cytoprotective agents offer opportunities to reduce treatment related toxicity of anticancer therapy without diminution of efficacy. None of the available agents satisfy criteria for an ideal cytoprotection. This has stimulated research for discovering natural resources with immunomodulatory and cytoprotective activities. This article describes chemical agents presently employed in clinical practice and reviews ethnopharmacological agents reported to have chemoprotective, radioprotective, immunomodulating, adaptogenic and antitumour activities.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 6","pages":"479-90"},"PeriodicalIF":0.0,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011043352704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844683","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
Antifolates -- past, present and future. 抗叶酸药——过去、现在和未来。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352803
Aleem Gangjee, Hiteshkumar D Jain
{"title":"Antifolates -- past, present and future.","authors":"Aleem Gangjee,&nbsp;Hiteshkumar D Jain","doi":"10.2174/1568011043352803","DOIUrl":"https://doi.org/10.2174/1568011043352803","url":null,"abstract":"<p><p>This short perspective briefly covers selected aspects of the past, present and future of antifolates in chemotherapy. Both classical and nonclassical analogs currently in the preclinical stage and clinically used agents are covered.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"405-10"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24693252","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: 8
Modelling and simulation: a computational perspective in anticancer drug discovery. 建模和模拟:抗癌药物发现的计算视角。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352786
Federico Gago
{"title":"Modelling and simulation: a computational perspective in anticancer drug discovery.","authors":"Federico Gago","doi":"10.2174/1568011043352786","DOIUrl":"https://doi.org/10.2174/1568011043352786","url":null,"abstract":"<p><p>The availability of high-quality molecular graphics tools in the public domain is changing the way macromolecular structure is perceived by researchers, educators and students alike. Computational methods have become increasingly important in a number of areas such as comparative or homology modelling, functional site location, characterization of ligand-binding sites in proteins, docking of small molecules into protein binding sites, protein-protein docking, and molecular dynamics simulations. The results obtained yield information that sometimes is beyond current experimental possibilities and can be used to guide and improve a vast array of experiments. On the basis of our improved level of understanding of molecular recognition and the widespread availability of target structures, it is reasonable to assume that computational methods will continue aiding not only in the design and interpretation of hypothesis-driven experiments in the field of cancer research but also in the rapid generation of new hypotheses.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"401-3"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24693251","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: 12
Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints. 喜树碱和拓扑异构酶I:迈出了第一步。用喜树碱和新型抗癌药物靶向拓扑异构酶I以外的基因组:DNA复制、修复和细胞周期检查点的重要性。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352777
Yves Pommier
{"title":"Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints.","authors":"Yves Pommier","doi":"10.2174/1568011043352777","DOIUrl":"https://doi.org/10.2174/1568011043352777","url":null,"abstract":"<p><p>Camptothecins selectively target topoisomerase I (Top1) by trapping the catalytic intermediate of the Top1-DNA reaction, the cleavage complex. Hence, camptothecins represent a paradigm for targeting macromolecular interactions. Instead of preventing the binding of the two macromolecules they target (Top1 and DNA), camptothecins slow down the dissociation of these macromolecules. The activity of camptothecins underlines the usefulness of screening for drugs that inhibit the dissociation of macromolecules. Camptothecins and non-CPT Top1 inhibitors are being developed to improve the pharmacodynamics, pharmacokinetics and clinical pharmacology of camptothecins, and it is likely that drugs with improved anticancer activity will be discovered. Although Top1 is the only primary target of camptothecins, the mechanisms of camptothecins' anticancer activity rest beyond the formation of cleavage complexes. Indeed, Top1 cleavage complexes lead to replication- (and transcription-) mediated DNA damage. It is likely that DNA damage can be repaired more efficiently in normal than in cancer cells that are intrinsically deficient for DNA repair and cell cycle checkpoints. Evaluating such deficiencies in clinical samples is becoming possible. If specific deficiencies are associated with clinical responses, their detection should guide therapeutic decisions. Furthermore, targeting DNA repair (Tdp1) and checkpoints (ATM, Chk1 and Chk2) might increase the selectivity of Top1 inhibitors for tumors, thereby increasing the antitumor activity while reducing the side effects of Top1 inhibitors.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"429-34"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011043352777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24691736","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: 95
G-quadruplex interacting agents targeting the telomeric G-overhang are more than simple telomerase inhibitors. 针对端粒g -悬垂的g -四联体相互作用剂不仅仅是简单的端粒酶抑制剂。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352740
Jean-Fraņois Riou
{"title":"G-quadruplex interacting agents targeting the telomeric G-overhang are more than simple telomerase inhibitors.","authors":"Jean-Fraņois Riou","doi":"10.2174/1568011043352740","DOIUrl":"https://doi.org/10.2174/1568011043352740","url":null,"abstract":"<p><p>The extremities of chromosomes end at telomeres in a G-rich single stranded overhang that may adopt peculiar structures such as T-loop and G-quadruplex. G-quadruplex is a poor substrate for telomerase activity and different classes of small molecule ligands that selectively stabilize this structure and inhibit telomerase activity have been selected by screening or synthesized by oriented chemistry. These ligands differ from catalytic inhibitors of telomerase by several points that were discussed in the present review, with a special emphasis on their biological activity as potential antitumor agents.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"439-43"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24691738","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: 60
Prospects for hypoxia-activated anticancer drugs. 低氧活化抗癌药物的前景。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352812
William A Denny
{"title":"Prospects for hypoxia-activated anticancer drugs.","authors":"William A Denny","doi":"10.2174/1568011043352812","DOIUrl":"https://doi.org/10.2174/1568011043352812","url":null,"abstract":"<p><p>The occurrence of hypoxic cells in solid tumors, and their resistance to radiotherapy and many chemotherapeutic drugs, has engendered an interest in non-toxic prodrugs that can be activated selectively under hypoxic conditions. Despite this, no such compounds are yet registered for clinical use, due to the difficulty of their design and of measuring the extent of hypoxia clinically, and the failure of early examples. A new appreciation of the critical importance of the extravascular diffusion of the parent prodrug from the blood vessels to the remote hypoxic cells, and the back-diffusion of the activated cytotoxin from the hypoxic cells to surrounding tumor cells, is now guiding drug design in this area. New principles for the selective activation of prodrugs have also been reported, including using the reducing species generated in cells by radiotherapy itself, and using non-pathogenic anaerobic bacteria as a hypoxia-dependent vector for the delivery of prodrug-activating enzymes in a suicide gene therapy context.</p>","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"395-9"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24693250","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: 29
Tumor cell resistance to DNA-damaging agents: from apoptosis to neiosis. 肿瘤细胞对dna损伤剂的抵抗:从凋亡到坏死。
Current medicinal chemistry. Anti-cancer agents Pub Date : 2004-09-01 DOI: 10.2174/1568011043352768
François Martin, Eric Solary
{"title":"Tumor cell resistance to DNA-damaging agents: from apoptosis to neiosis.","authors":"François Martin,&nbsp;Eric Solary","doi":"10.2174/1568011043352768","DOIUrl":"https://doi.org/10.2174/1568011043352768","url":null,"abstract":"","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"4 5","pages":"461-3"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24755343","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: 9
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