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  3. Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents

Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents

  • Eur J Med Chem. 2020 Jul 15;198:112360. doi: 10.1016/j.ejmech.2020.112360.
Hang Xu 1,  Xin Su 2,  Meng-Bi Guo 1,  Ran An 1,  Yan-Hua Mou 2,  Zhuang Hou 3,  Chun Guo 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 2 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 3 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: houzhuang8@sina.com.
  • 4 Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: gc_66888@163.com.
PMID: 32403018 DOI: 10.1016/j.ejmech.2020.112360
Abstract

Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant Antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent inhibitory effects on fluconazole-resistant fungi. Subsequently, preliminary mechanistic studies indicated that the representative compound A03 had a strong inhibitory effect on C.alb. CYP51. Moreover, the target compounds could prevent the formation of fungi biofilms. Further hemolysis test verified that potential compounds had higher safety than miconazole. In addition, molecular docking study provided the interaction modes between the target compounds and C.alb. CYP51. These results strongly suggested that some target compounds are promising as novel Antifungal drugs.

Keywords

Antifungal; Bioisosterism; CYP51; Miconazole; Selenium.

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