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由于唑类药物长期使用,真菌耐药性及其交叉耐药现象不断出现,对临床治疗具有重要威胁。近年来提出新型抗真菌药物的新靶点,并研发出具有高活性强、强疗效的抗真菌药物。本研究对近年来新型抗真菌药的种类、结构和特点进行阐述,并介绍不同型药物对真菌的细胞壁、细胞膜、蛋白质合成、呼吸链等作用新靶点和作用机制的研究进展。 相似文献
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真菌的多向耐药性ABC转运蛋白(ATP-binding cassette transporters)是导致多药耐药性和抗真菌药物治疗效果明显下降的主要原因。文章对酿酒酵母(Saccharomyces cerevisiae)和主要致病真菌白色假丝酵母(Candida albicans)、新型隐球酵母(Cryptococcus neoformans)和烟曲霉(Aspergillus fumigatus)中的多向耐药性ABC转运蛋白的种类、药物外排机制以及基因表达调控网络的研究进展作一综述,为深入了解真菌的多向耐药性机制以及探讨克服多向耐药性的策略和提高药效提供参考。 相似文献
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侵袭性真菌感染(invasive fungal infections,IFI)以其逐年上升的发病率和致死率,已经成为人类健康的严重威胁。临床常用的抗真菌药物包括氮唑类、多烯类以及棘白菌素类等。药物治疗作为应对IFI的主要策略,现有的药物种类明显不足,并且受到真菌耐药性和药物毒副作用等越来越多的制约,使得对抗真菌新药的需求愈加迫切。新型抗真菌药物的研发策略主要包括改造现有临床常用药物和发现新靶点药物两个方面。近年值得关注的研发中的新型抗真菌药物包括:氮唑类药物VT-1161和VT-1129、葡聚糖合成酶抑制剂CD101和SCY-078、GPI锚合成抑制剂E1210、嘧啶合成抑制剂F901318、抗真菌中药和增效剂,以及其他抗真菌新药如T-2307、尼可霉素Z和VL-2397等。该文主要综述了上述新药的研究进展,包括作用机制、体内外活性以及临床试验等。 相似文献
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近20多年来,随着免疫缺陷患者的增多,侵袭性真菌感染发病率呈持续上升趋势,死亡率高居不下。现用的抗真菌药物主要有氮唑类、多烯类、棘白菌素类等,存在品种少、真菌耐药性增加和毒副作用大等问题,迫切需要研制新型抗真菌药物。单克隆抗体具有精准靶向的抗真菌作用,兼有调节机体免疫反应的功能,是治疗真菌感染的一种可行且具有独特优势的药物。从作用靶点分类,可以分为靶向真菌表面多糖、毒力因子、蛋白和跨界抗真菌单克隆抗体。从抗体来源分类又可以分为天然抗体和重组抗体。其作用机制包括直接抗真菌作用,即对毒素中和或对真菌的直接抑制作用;以及免疫增强作用,主要是补体的活化以驱动吞噬细胞清除或破坏致病真菌、中性粒细胞调理吞噬作用的激活以及诱导巨噬细胞调理吞噬。本文从药效学等方面总结了目前抗真菌感染单克隆抗体的研究进展,以及存在的问题。此外,针对抗真菌单克隆抗体的新型制备方法与传统制备方法进行了对比,并探讨了未来的发展方向。 相似文献
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Lipid-based antifungal agents 总被引:2,自引:0,他引:2
Arikan S 《Cellular & molecular biology letters》2002,7(2):220-221
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Quesnelle CA Gill P Dodier M St Laurent D Serrano-Wu M Marinier A Martel A Mazzucco CE Stickle TM Barrett JF Vyas DM Balasubramanian BN 《Bioorganic & medicinal chemistry letters》2003,13(3):519-524
Compounds based on sordaricin were prepared via organometallic addition onto a fully protected sordaricin aldehyde. The fungal growth inhibition profiles for these compounds were established and the results are presented here. The synthesis of homologated sordaricin as well as ether and ester derivatives is presented, and structural rearrangement products upon oxidation. These compounds were evaluated as agents to inhibit fungal growth. 相似文献
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解淀粉芽孢杆菌抗菌活性物质的分离纯化及抑菌活性研究 总被引:5,自引:0,他引:5
植物真菌病害给农业生产带来了巨大损失,因此对生物农药的开发迫在眉睫。从堆肥中分离得到一株解淀粉芽孢杆菌,它具有强烈的抗真菌活性。其发酵液经硫酸胺沉淀得到粗提液,粗提液经Hiprep 26/10 Desalting,HiLoad 26/10 Q Sepharose和HPLC多步柱层析,分离纯化得到一种抗真菌活性物质。ESI-MS质谱法测得其分子量为1498 Da。经活性检测发现,该纯物质对尖孢镰刀菌、草莓蛇病菌等植物病原真菌具有很强的抑制作用,对毛霉、黑曲霉等食品腐败菌也有抑制作用。经过显微镜观测,该物质可造成草莓蛇病菌菌丝生长异常,表现在菌丝弯曲,顶端膨大,分生孢子数量减少。 相似文献
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6种抗真菌药物对皮肤癣菌体外抗真菌活性评价 总被引:1,自引:1,他引:0
目的评价6种抗真菌药物对皮肤癣菌体外抗真菌活性。方法采用CLSI推荐的M-38P方案对分离自足癣和体、股癣的皮肤癣菌进行联苯苄唑、硝酸舍他康唑、硝酸异康唑、盐酸布替萘芬、阿莫洛芬、利拉萘酯6种抗真菌药物敏感性测定。结果联苯苄唑MIC范围为0.03—4mg/L,MIC50为1mg/L,MIC90为2mg/L。硝酸舍他康唑分别为0.06—16mg/L、0.5mg/L和2mg/L。硝酸异康唑分别为0.03~2mg/L、0.25mg/L和0.5mg/L。盐酸布替萘芬分别为0.0025~0.04mg/L、0.01mg/L和0.02mg/L。阿莫罗芬分别为0.01~〉0.08mg/L、0.02mg/L和0.04mg/L。利拉萘酯分别为0.004—0.625mg/L、0.039mg/L和0.312mg/L。结论6种抗真菌药物对皮肤癣菌均有强的抗菌活性,由强到弱依次为布替萘芬、阿莫罗芬、利拉萘酯和咪唑类药物。 相似文献
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覆盆子提取物联合唑类药物抗真菌活性研究 总被引:1,自引:1,他引:1
目的 探讨中药覆盆子提取物联合唑类药物的体外抗真菌作用.方法 采用CLSI公布的M27-A方案微量液基稀释法和棋盘式微量稀释法,测定覆盆子提取物单用及联合唑类药物对不同念珠菌的MIC值和FICI指数.结果 覆盆子不同溶液提取物与氟康唑均表现出协同关系,以覆盆子醇提物为例,单用对念珠菌的MIC80测定值范围主要集中在0.16~1.25 mg/mL,与氟康唑合用后表现出协同关系(FICI≤0.5),且MIC80测定值范围降至0.01 ~0.04 mg/mL;合用后的氟康唑抗真菌活性也明显增强.另外,覆盆子醇提物与不同唑类药物合用后均有协同关系,其MIC80测定值由单用时大于10 mg/mL降至0.04 mg/mL.结论 覆盆子醇提物和唑类药物单用时对耐药念珠菌的抑菌作用较弱,但二者合用后表现出明显的协同关系,对耐药念珠菌的抑菌作用明显增强. 相似文献
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《Fungal Biology Reviews》2013,27(4):156-165
There remains an urgent and very much unmet medical need for new antifungal therapies. Ideally, the next generation of treatments for nosocomial and community-acquired infections, including those caused by Candida spp, Aspergillus spp, Cryptococcus spp and Fusarium spp, will be more efficacious, with higher therapeutic indices and broader activity spectra than existing antifungal drug classes. Moreover, future antifungal therapeutics should have novel modes of action/drug targets that at least minimise, if not negate, the risk of acquired resistance developing in their target fungal pathogen populations. In short, developing the next generation of antifungals is a tall order and whoever is successful in doing so must address the various and well-described shortcomings of what remains at present, a very limited choice of largely small molecule-based therapeutics against the fungal infection spectrum. Novel peptide antifungals engineered from a template of mammalian, amphibian and even insect endogenous antimicrobial peptides (AMPs) have clear potential to meet these requirements and consequent clinical success in a range of fungal diseases. This potential will hopefully be realised in the future as any number of the promising preclinical candidate antifungal peptides identified to date are developed further towards the clinic. The size of the ever-increasing market potential as well as unmet clinical need for new antifungal treatments is such that succeeding in delivering novel peptide antifungals as safe and potently efficacious therapies for the future will have a significant health-economic impact. 相似文献
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《Fungal Biology Reviews》2012,26(4):156-165
There remains an urgent and very much unmet medical need for new antifungal therapies. Ideally, the next generation of treatments for nosocomial and community-acquired infections, including those caused by Candida spp, Aspergillus spp, Cryptococcus spp and Fusarium spp, will be more efficacious, with higher therapeutic indices and broader activity spectra than existing antifungal drug classes. Moreover, future antifungal therapeutics should have novel modes of action/drug targets that at least minimise, if not negate, the risk of acquired resistance developing in their target fungal pathogen populations. In short, developing the next generation of antifungals is a tall order and whoever is successful in doing so must address the various and well-described shortcomings of what remains at present, a very limited choice of largely small molecule-based therapeutics against the fungal infection spectrum. Novel peptide antifungals engineered from a template of mammalian, amphibian and even insect endogenous antimicrobial peptides (AMPs) have clear potential to meet these requirements and consequent clinical success in a range of fungal diseases. This potential will hopefully be realised in the future as any number of the promising preclinical candidate antifungal peptides identified to date are developed further towards the clinic. The size of the ever-increasing market potential as well as unmet clinical need for new antifungal treatments is such that succeeding in delivering novel peptide antifungals as safe and potently efficacious therapies for the future will have a significant health-economic impact. 相似文献
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Vanden Bossche H 《Revista iberoamericana de micología》1997,14(2):44-49
The many drugs that are available at present to treat fungal infections can be divided into four broad groups on the basis of their mechanism of action. These antifungal agents either inhibit macromolecule synthesis (flucytosine), impair membrane barrier function (polyenes), inhibit ergosterol synthesis (allylamines, thiocarbamates, azole derivatives, morpholines), or interact with microtubules (griseofulvin). Drug resistance has been identified as the major cause of treatment failure among patients treated with flucytosine. A lesion in the UMP-pyrophosphorylase is the most frequent clinical determinant of resistance to 5FC in Candida albicans. Despite extensive use of polyene antibiotics for more than 30 years, emergence of acquired resistance seems not be a significant clinical problem. Polyene-resistant Candida isolates have a marked decrease in their ergosterol content. Acquired resistance to allylamines has not been reported from human pathogens, but, resistant phenotypes have been reported for variants of Saccharomyces cerevisiae and of Ustilago maydis. Tolerance to morpholines is seldom found. Intrinsic resistance to griseofulvin is due to the absence of a prolonged energy-dependent transport system for this antibiotic. Resistance to azole antifungal agents is known to be exceptional, although it does now appear to be increasing in importance in some groups of patients infected with e.g. Candida spp., Histoplasma capsulatum or Cryptococcus neoformans. For example, resistance to fluconazole is emerging in C. albicans, the major agent of oro-pharyngeal candidosis in AIDS patients, after long-term suppressive therapy. In the majority of cases, primary and secondary resistance to fluconazole and cross-resistance to other azole antifungal agents seems to originate from decreased intracellular accumulation of the azoles, which may result from reduced uptake or increased efflux of the molecules. In most C. albicans isolates the decreased intracellular levels can be correlated with enhanced azole efflux, a phenomenon linked to an increase in the amounts of mRNA of a C. albicans ABC transporter gene CDR1 and of a gene (BEN(r) or CaMDR) coding for a transporter belonging to the class of major facilitator multidrug efflux transporters. Not only fluconazole, ketoconazole and itraconazole are substrates for CDR1, terbinafine and amorolfine have also been established as substrates, BEN(r) overexpression only accounts for fluconazole resistance. Other sources of resistance: changes in membrane sterols and phospholipids, altered or overproduced target enzyme(s) and compensatory mutations in the Delta5,6-desaturase. 相似文献