Antifungal triazoles

  • 文章类型: Journal Article
    侵袭性真菌感染(IFIs)和卵菌病(以下称为侵袭性真菌样感染[IFLIs])的特征在于真菌成分对组织的渗透。环境是最常见的感染库。IFIs和IFLIs治疗可能令人沮丧,因为通常需要较长的治疗时间,即使在达到临床治愈之后,可能有复发的风险。随着时间的推移,业主对药物管理和重新检查检查的依从性也会下降。此外,一些抗真菌药物很贵,具有可变的患者间药代动力学特性,只能肠胃外给药和/或具有常见的不良反应(AE)。尽管有这些限制,治疗可以是非常有益的,尤其是当一种进行性和致命的疾病被治愈时。
    在由两部分组成的文章系列的第二部分中,活动的频谱,行动机制,药代动力学和药效学特性,并对抗真菌药物的不良事件进行了综述,以及特异性IFIs/IFLIs的治疗和预后-皮肤癣菌假单胞菌瘤,隐球菌病,中国轨道曲霉病,球孢子菌病,组织胞浆菌病,孢子丝菌病,phaeophyphysp真菌病,毛霉菌病和卵菌病-进行了讨论。第1部分回顾了IFIs和IFLIs的诊断方法。
    抗真菌药物的信息来自猫的药代动力学研究。如果尚未进行此类研究,对来自“临床前”动物(非人类研究)和人类研究的数据进行了综述。该评论还借鉴了更广泛的已发表证据和作者在猫科动物医学方面的综合专业知识,真菌学,皮肤病学,临床病理学和解剖学病理学。
    AMB(两性霉素B);FC(氟胞嘧啶);FCZ(氟康唑);ISA(异氟康唑);ITZ(伊曲康唑);KCZ(酮康唑);PCZ(泊沙康唑);TRB(特比萘芬);VCZ(伏立康唑)。
    Invasive fungal infections (IFIs) and oomycoses (hereafter termed invasive fungal-like infections [IFLIs]) are characterised by penetration of tissues by fungal elements. The environment is the most common reservoir of infection. IFIs and IFLIs can be frustrating to treat because long treatment times are usually required and, even after attaining clinical cure, there may be a risk of relapse. Owner compliance with medication administration and recheck examinations can also decline over time. In addition, some antifungal drugs are expensive, have variable interpatient pharmacokinetic properties, can only be administered parenterally and/or have common adverse effects (AEs). Despite these limitations, treatment can be very rewarding, especially when an otherwise progressive and fatal disease is cured.
    In the second of a two-part article series, the spectrum of activity, mechanisms of action, pharmacokinetic and pharmacodynamic properties, and AEs of antifungal drugs are reviewed, and the treatment and prognosis of specific IFIs/IFLIs - dermatophytic pseudomycetoma, cryptococcosis, sino-orbital aspergillosis, coccidioidomycosis, histoplasmosis, sporotrichosis, phaeohyphomycosis, mucormycosis and oomycosis - are discussed. Part 1 reviewed the diagnostic approach to IFIs and IFLIs.
    Information on antifungal drugs is drawn from pharmacokinetic studies in cats. Where such studies have not been performed, data from \'preclinical\' animals (non-human studies) and human studies are reviewed. The review also draws on the wider published evidence and the authors\' combined expertise in feline medicine, mycology, dermatology, clinical pathology and anatomical pathology.
    AMB (amphotericin B); FC (flucytosine); FCZ (fluconazole); ISA (isavuconazole); ITZ (itraconazole); KCZ (ketoconazole); PCZ (posaconazole); TRB (terbinafine); VCZ (voriconazole).
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  • 文章类型: Journal Article
    肽模拟物在药物设计中起着重要的作用,这是由于它们对天然肽的优先性质。特别是,近年来,人们对具有含氮杂环的化合物进行了深入的研究。三唑基部分的掺入降低了分子对酶降解的敏感性,reduction,水解,和氧化。事实上,含三唑环的肽是肽模拟物的典型实例。它们具有优于经典肽的所有优点。有效的合成方法和生物活性都使这些系统成为有趣且有前途的研究对象。肽三唑衍生物显示出多样性的生物学特性,并且可以通过多种合成策略获得。在这次审查中,我们强调了三唑修饰的模拟肽在药物设计领域的重要性.我们概述了含三唑基拟肽合成的新成就及其作为酶抑制剂或抗癌的生物活性。病毒,细菌,或真菌。上述化合物的相关性通过它们与未修饰的肽的比较得到证实。
    Peptidomimetics play a fundamental role in drug design due to their preferential properties regarding natural peptides. In particular, compounds possessing nitrogen-containing heterocycles have been intensively studied in recent years. The triazolyl moiety incorporation decreases the molecule susceptibility to enzymatic degradation, reduction, hydrolysis, and oxidation. In fact, peptides containing triazole rings are a typical example of peptidomimetics. They have all the advantages over classic peptides. Both efficient synthetic methods and biological activity make these systems an interesting and promising object of research. Peptide triazole derivatives display a diversity of biological properties and can be obtained via numerous synthetic strategies. In this review, we have highlighted the importance of the triazole-modified peptidomimetics in the field of drug design. We present an overview on new achievements in triazolyl-containing peptidomimetics synthesis and their biological activity as inhibitors of enzymes or against cancer, viruses, bacteria, or fungi. The relevance of above-mentioned compounds was confirmed by their comparison with unmodified peptides.
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