2. Academic Validation
  3. Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents

Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents

  • Eur J Med Chem. 2022 Jan 15;228:113987. doi: 10.1016/j.ejmech.2021.113987.
Liyu Zhao 1,  Yin Sun 1,  Wenbo Yin 1,  Linfeng Tian 1,  Nannan Sun 1,  Yang Zheng 1,  Chu Zhang 1,  Shizhen Zhao 2,  Xin Su 3,  Dongmei Zhao 4,  Maosheng Cheng 1
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
  • 2 Key Laboratory of Receptor-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, 475004, China.
  • 3 The School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
  • 4 Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China. Electronic address: medchemzhao@163.com.
PMID: 34801270 DOI: 10.1016/j.ejmech.2021.113987
Abstract

To discover Antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum Antifungal activity against Candida albicans with MIC values in the range of 0.03-0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25-2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.

Keywords

4,5-dihydrooxazole; Azole antifungals; Broad-spectrum; CYP51.

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