2. Academic Validation
  3. Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi

Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi

  • Eur J Med Chem. 2021 Dec 5:225:113740. doi: 10.1016/j.ejmech.2021.113740.
Wenbo Yin 1,  Yuxin Zhang 1,  Hengxian Cui 1,  Hong Jiang 1,  Lei Liu 1,  Yang Zheng 1,  Tianxiao Wu 1,  Liyu Zhao 1,  Yin Sun 1,  Xin Su 2,  Song Li 3,  Dongmei Zhao 4,  Maosheng Cheng 1
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
  • 2 The School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China. Electronic address: lis.lisong@gmail.com.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China. Electronic address: medchemzhao@163.com.
PMID: 34388384 DOI: 10.1016/j.ejmech.2021.113740
Abstract

A series of 5-phenylthiophene derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible and drug-resistant Fungal infections. The Antifungal activity of the synthesized compounds was assessed against seven susceptible strains and six fluconazole-resistant strains. It is especially encouraging that compounds 17b and 17f displayed significant Antifungal activities against all tested strains. Furthermore, the potent compounds 17b and 17f could prevent the formation of fungi biofilms and 17f displayed satisfactory fungicidal activity. Preliminary mechanistic studies showed that the potent Antifungal activity of compound 17f stemmed from inhibition of C. albicans CYP51. In addition, Compounds 17b and 17f were almost nontoxic to mammalian A549, MCF-7, and THLE-2 cells. These results strongly suggested that compounds 17b and 17f are promising as novel Antifungal drugs.

Keywords

Azole antifungals; CYP51; Fluconazole-resistance; Fungicidal agents.

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