Current medicinal chemistry. Anti-cancer agents最新文献

Inhibition of PI3K/Akt signaling: an emerging paradigm for targeted cancer therapy. 抑制PI3K/Akt信号:靶向癌症治疗的新模式

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574649

Yulong L Chen, Ping-Y Law, Horace H Loh

{"title":"Inhibition of PI3K/Akt signaling: an emerging paradigm for targeted cancer therapy.","authors":"Yulong L Chen, Ping-Y Law, Horace H Loh","doi":"10.2174/156801105774574649","DOIUrl":"https://doi.org/10.2174/156801105774574649","url":null,"abstract":"The phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B, PKB) signaling pathway plays a critical role in cell growth and survival. Dysregulation of this pathway has been found in a variety of cancer cells. Recently, constitutively active PI3K/Akt signaling has been firmly established as a major determinant for cell growth and survival in an array of cancers. Blocking the constitutively active PI3K/AKT signaling pathway provides a new strategy for targeted cancer therapy. Thus, inhibitors of this signaling pathway would be potential anticancer agents, particularly for cancer cells whose survival and growth are dominated by constitutively active PI3K/Akt signaling. This review describes the current understanding of small molecule drugs targeting this pathway both in vitro and in vivo. Inhibitors and functions of the upstream and downstream molecular targets of the PI3K/Akt pathway are discussed in the context of using the inhibitors to block this pathway for targeted cancer therapy. Special emphasis is placed on the following targets: receptor tyrosine kinases, PI3K, Akt, and the mammalian target of rapamycin. While the molecular therapeutic strategy holds great promise for the treatment of a variety of cancers, few small molecule inhibitors with potential high therapeutic indexes are available. Thus, new inhibitors with high selectivity, bioavailability, and potency are greatly needed. Novel approaches toward the development of PI3K/Akt pathway inhibitors as anticancer therapeutics are discussed in detail, with emphasis on chemical genetics-based and structure-based drug design.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 6","pages":"575-89"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801105774574649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25702563","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: 107

Sulfo-quinovosyl-acyl-glycerol (SQAG), a eukaryotic DNA polymerase inhibitor and anti-cancer agent. 磺基喹啉酰基甘油(SQAG)，真核DNA聚合酶抑制剂和抗癌剂。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574685

Yoshiyuki Mizushina, Nobuyuki Kasai, Hiroshi Iijima, Fumio Sugawara, Hiromi Yoshida, Kengo Sakaguchi

{"title":"Sulfo-quinovosyl-acyl-glycerol (SQAG), a eukaryotic DNA polymerase inhibitor and anti-cancer agent.","authors":"Yoshiyuki Mizushina, Nobuyuki Kasai, Hiroshi Iijima, Fumio Sugawara, Hiromi Yoshida, Kengo Sakaguchi","doi":"10.2174/156801105774574685","DOIUrl":"https://doi.org/10.2174/156801105774574685","url":null,"abstract":"It was found that a class of sulfolipids known as sulfo-quinovosyl-acyl-glycerols (SQAGs) from ferns and algae are potent inhibitors of eukaryotic DNA polymerase alpha and beta and effective anti-neoplastic agents. In developing a procedure for the chemical synthesis of sulfolipids, many derivatives and stereoisomers of SQAGs have been obtained including sulfo-quinovosyl-monoacyl-glycerols (SQMGs) and sulfo-quinovosyl-diacyl-glycerols (SQDGs). This review describes studies on the structure-function relationship between synthetic SQAGs and DNA polymerase alpha and beta, and the relationship to cytotoxic activity. The major action was probably dependent on the fatty acid effect, which was reported previously, although each of the SQAGs was a much stronger inhibitor than just the fatty acid present in the SQAGs. The inhibitory effect could be influenced by the chain size of fatty acids in the SQAGs. The sulfonyl group in quinovose was also needed to inhibit the enzymes. Lineweaver-Burk plots of SQAGs indicated that DNA polymerase alpha was non-competitively inhibited, but the SQAGs were effective as antagonists of both the template-primer DNA-binding and the nucleotide substrate-binding of DNA polymerase beta. Based on these results, the molecular actions of SQAGs and drug design strategies for developing new anti-neoplastic agents were discussed.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 6","pages":"613-25"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801105774574685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25702566","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

Selenium derivatives as cancer preventive agents. 硒衍生物作为防癌剂。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574676

Tarek Aboul-Fadl

引用次数: 27

Current drug therapy for prostate cancer: an overview. 目前前列腺癌的药物治疗综述。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574658

Alistair B Stewart, Bashir A Lwaleed, David A Douglas, Brian R Birch

引用次数: 26

Lanthanides as anticancer agents. 镧系元素作为抗癌剂。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574694

Irena Kostova

{"title":"Lanthanides as anticancer agents.","authors":"Irena Kostova","doi":"10.2174/156801105774574694","DOIUrl":"https://doi.org/10.2174/156801105774574694","url":null,"abstract":"The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metals and metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. A lot of metal-based drugs are widely used in the treatment of cancer. The clinical success of cisplatin and other platinum complexes is limited by significant side effects acquired or intrinsic resistance. Therefore, much attention has focused on designing new coordination compounds with improved pharmacological properties and a broader range of antitumor activity. Strategies for developing new anticancer agents include the incorporation of carrier groups that can target tumor cells with high specificity. Also of interest is to develop complexes that bind to DNA in a fundamentally different manner than cisplatin, in an attempt to overcome the resistance pathways that have evolved to eliminate the drug. This review focuses on recent advances in developing lanthanide anticancer agents with an emphasis on lanthanide coordination complexes. These complexes may provide a broader spectrum of antitumor activity. They were compared with classical platinum anticancer drugs. Lanthanides are also of interest because of their therapeutic radioisotopes. The dominant pharmacological applications of lanthanides are as agents in radioimmunotherapy and photodynamic therapy.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 6","pages":"591-602"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801105774574694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25702564","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: 88

Lycopene: a review of its potential as an anticancer agent. 番茄红素:其抗癌潜力的综述。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-11-01 DOI: 10.2174/156801105774574667

V Bhuvaneswari, S Nagini

{"title":"Lycopene: a review of its potential as an anticancer agent.","authors":"V Bhuvaneswari, S Nagini","doi":"10.2174/156801105774574667","DOIUrl":"https://doi.org/10.2174/156801105774574667","url":null,"abstract":"Dietary chemoprevention has emerged as a cost effective approach to control most prevalent chronic diseases including cancer. In particular, tomato and tomato products are recognised to confer a wide range of health benefits. Epidemiological studies have provided evidence that high consumption of tomatoes effectively lowers the risk of reactive oxygen species (ROS)-mediated diseases such as cardiovascular disease and cancer by improving the antioxidant capacity. Tomatoes are rich sources of lycopene, an antioxidant carotenoid reported to be a more stable and potent singlet oxygen quenching agent compared to other carotenoids. In addition to its antioxidant properties, lycopene shows an array of biological effects including cardioprotective, anti-inflammatory, antimutagenic and anticarcinogenic activities. The anticancer activity of lycopene has been demonstrated both in in vitro and in vivo tumour models. The mechanisms underlying the inhibitory effects of lycopene on carcinogenesis could involve ROS scavenging, upregulation of detoxification systems, interference with cell proliferation, induction of gap-junctional communication, inhibition of cell cycle progression and modulation of signal transduction pathways. This review outlines the sources, structure, absorption, metabolism, bioavailability and pharmacological properties of lycopene with special reference to its antioxidant and anticarcinogenic effects.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 6","pages":"627-35"},"PeriodicalIF":0.0,"publicationDate":"2005-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156801105774574667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25702567","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: 142

Quadruplex-forming oligonucleotides as tools in anticancer therapy and aptamers design: energetic aspects. 四聚体形成寡核苷酸作为抗癌治疗和适体设计的工具:能量方面。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866900

L Petraccone, G Barone, C Giancola

引用次数: 19

Histone deacetylase inhibitors: latest developments, trends and prospects. 组蛋白去乙酰化酶抑制剂:最新进展、趋势和前景。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866946

Oscar Moradei, Christiane R Maroun, Isabelle Paquin, Arkadii Vaisburg

引用次数: 73

Sesquiterpenes: natural products that decrease cancer growth. 倍半萜:减少癌症生长的天然产物。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866973

Aneta Modzelewska, Surojit Sur, Srinivas K Kumar, Saeed R Khan

{"title":"Sesquiterpenes: natural products that decrease cancer growth.","authors":"Aneta Modzelewska, Surojit Sur, Srinivas K Kumar, Saeed R Khan","doi":"10.2174/1568011054866973","DOIUrl":"https://doi.org/10.2174/1568011054866973","url":null,"abstract":"Despite recent advances in our understanding of the biological processes leading to the development of cancer, there is still a need for new and effective agents to help bring this disease under control. One of the oldest and most effective strategies for developing new chemotherapeutics is the isolation and evaluation of chemicals of natural origin. The importance of natural products for drug discovery has been impressive: One has to only look at the number of clinically active drugs that are used in cancer therapy to see how many are either natural products or are based on natural products. It is also apparent that materials from natural sources are excellent probes (indicators) for cellular targets that, when modulated, may have a deleterious effect upon the survival or proliferation of tumor cells. And the search goes on. Sesquiterpenes are a class of naturally occurring molecules that have demonstrated therapeutic potential in decreasing the progression of cancer. These molecules are 15-carbon isoprenoid compounds that are typically found in plants and marine life. Although this class of compounds has frequently provided encouraging leads for chemotherapeutics, they have not been evaluated as potential anticancer agents. In this review, we provide a current overview of sesquiterpenoids that have potential as anticancer agents.","PeriodicalId":10914,"journal":{"name":"Current medicinal chemistry. Anti-cancer agents","volume":"5 5","pages":"477-99"},"PeriodicalIF":0.0,"publicationDate":"2005-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568011054866973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25600002","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: 103

Fundamental, electron transfer mechanism by pyrylium-type ions for the anticancer drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone-8-acetic acid (FAA). 吡啶类离子对抗癌药物5,6-二甲基黄酮-4-乙酸(DMXAA)和黄酮-8-乙酸(FAA)的基本电子转移机制。

Current medicinal chemistry. Anti-cancer agents Pub Date : 2005-09-01 DOI: 10.2174/1568011054866919

Peter Kovacic

引用次数: 10