Antifungal Agents: Design, Synthesis, Antifungal Activity and Molecular Docking of Phloroglucinol Derivatives

Molecules

Yuanyuan Wang¹  Xingxing Teng¹  Lianbao Ye¹  Peiqi Shi¹  Jinhua Gu¹  Zhibin Shen² 

[1] School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China;School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;

关键词: phloroglucinol derivatives;    antifungal activity;    molecular docking;    allylamine;    squalene epoxidase;   

DOI  :  10.3390/molecules23123116

来源: DOAJ

【 摘 要 】

Pseudoaspidinol is a phloroglucinol derivative with Antifungal activity and is a major active component of Dryopteris fragrans. In our previous work, we studied the total synthesis of pseudoaspidinol belonging to a phloroglucinol derivative and investigated its antifungal activity as well as its intermediates. However, the results showed these compounds have low antifungal activity. In this study, in order to increase antifungal activities of phloroglucinol derivatives, we introduced antifungal pharmacophore allylamine into the methylphloroglucinol. Meanwhile, we remained C1⁻C4 acyl group in C-6 position of methylphloroglucinol using pseudoaspidinol as the lead compound to obtain novel phloroglucinol derivatives, synthesized 17 compounds, and evaluated antifungal activities on Trichophyton rubrum and Trichophyton mentagrophytes in vitro. Molecular docking verified their ability to combine the protein binding site. The results indicated that most of the compounds had strong antifungal activity, in which compound 17 were found to be the most active on Trichophyton rubrum with Minimum Inhibitory Concentration (MIC) of 3.05 μg/mL and of Trichophyton mentagrophytes with MIC of 5.13 μg/mL. Docking results showed that compounds had a nice combination with the protein binding site. These researches could lay the foundation for developing antifungal agents of clinical value.

【 授权许可】

Unknown