Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Eur J Med Chem. 2019 May 15;170:173-194. doi: 10.1016/j.ejmech.2019.03.020. Epub 2019 Mar 11.
Currently, the available antifungal agents have significant clinical incompetency in terms of their clinical efficacy, antifungal spectrum, unfavorable pharmacokinetic profiles, substantial side effects and drug-drug interactions. Thus, the optimization and improvement of existing drugs and identification of new antifungal agents are urgently needed. Fluconazole is the first triazole alcohol drug with good in vivo efficacy against yeasts and well-known targets in fungal cells. However, the wide use of fluconazole as a first-line antifungal therapy has led to the development of resistance in clinical isolates of Candida species including Candida albicans and the emerging non-albicans Candida spp. In the last years, extensive efforts inflected to design and discovery of triazole alcohols derived from fluconazole by replacing one triazole ring with the proper side chain. In this paper, we have reviewed the structural modification of fluconazole to pursuit potent triazole alcohols with improved anti-Candida activity, and have highlighted their in vitro activities and in silico studies.
目前,可用的抗真菌药物在临床疗效、抗真菌谱、不良药代动力学特征、严重副作用和药物相互作用方面存在明显的临床缺陷。因此,迫切需要优化和改进现有药物并确定新的抗真菌药物。氟康唑是第一个具有良好体内抗酵母活性和真菌细胞中已知靶标的三唑醇类药物。然而,氟康唑作为一线抗真菌治疗药物的广泛应用导致念珠菌属包括白色念珠菌和新兴的非白色念珠菌念珠菌属的临床分离株产生了耐药性。在过去的几年中,人们进行了广泛的努力来设计和发现源自氟康唑的三唑醇类药物,通过用适当的侧链替换一个三唑环。在本文中,我们综述了氟康唑的结构修饰,以寻求具有改善抗念珠菌活性的强效三唑醇类药物,并强调了它们的体外活性和计算机研究。