Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
J Mycol Med. 2019 Sep;29(3):253-259. doi: 10.1016/j.mycmed.2019.07.004. Epub 2019 Jul 27.
The search for new antifungal strategies to overcome Candida infections is essential and a matter of public health, due to the high mortality associated to candidiasis, the increasing incidence of resistance to antifungals and the limited number of drugs available for treatment. Several approaches have been exploited in order to develop new antifungal strategies, e.g. the use of natural products, vaccines, and the combination of an antifungal drug to a non-antifungal substance. Nonetheless, issues related to pharmacokinetic parameters, toxicity and costs have been jeopardizing the discovery of new antifungal drugs. An alternative that could overcome these problems would be treating candidiasis with drugs that have been originally developed to treat other diseases. This strategy, known as drug repositioning or drug repurposing, could diminish the incidence of adverse effects and lower the cost of production, since several steps involved in drug discovery and development have already been accomplished. This review presents a set of known drugs that have been exploited as anticandidal agents, such as antidepressant agents, antiepileptic drugs, statins, among others. These substances affect the growth of Candida spp. in vitro, as well as virulence factors such as morphogenesis and biofilm formation. Moreover, some drugs are able to potentiate the anticandidal activity of known antifungal drugs. Drug repositioning appears as a remarkable alternative to increase the pharmacological arsenal against candidiasis, but further studies must be conducted in order to evaluate the real applicability of known drugs in the treatment of these infections.
寻找新的抗真菌策略以克服念珠菌感染至关重要，这是一个公共卫生问题，因为念珠菌病相关的死亡率高，抗真菌药物的耐药性不断增加，以及可用于治疗的药物数量有限。已经开发了几种方法来开发新的抗真菌策略，例如使用天然产物、疫苗和将抗真菌药物与非抗真菌物质联合使用。尽管如此，与药代动力学参数、毒性和成本相关的问题一直危及新抗真菌药物的发现。一种可以克服这些问题的替代方法是使用最初开发用于治疗其他疾病的药物来治疗念珠菌病。这种策略被称为药物重定位或药物再利用，可以减少不良反应的发生率并降低生产成本，因为药物发现和开发中已经完成了几个步骤。这篇综述介绍了一组已被用作抗念珠菌剂的已知药物，如抗抑郁药、抗癫痫药、他汀类药物等。这些物质在体外影响念珠菌属的生长，以及形态发生和生物膜形成等毒力因子。此外，一些药物能够增强已知抗真菌药物的抗真菌活性。药物重定位似乎是增加对抗念珠菌病的药理学武器的一种显著替代方法，但必须进行更多的研究，以评估已知药物在治疗这些感染中的实际适用性。
