title: Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism.
abstract: The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
authors: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors: Chunquan
authors: C
authors: Sheng
authors: Xiaoying
authors: X
authors: Che
authors: Wenya
authors: W
authors: Wang
authors: Shengzheng
authors: S
authors: Wang
authors: Yongbing
authors: Y
authors: Cao
authors: Zhenyuan
authors: Z
authors: Miao
authors: Jianzhong
authors: J
authors: Yao
authors: Wannian
authors: W
authors: Zhang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles