Synthesis, α-Glucosidase inhibition and molecular docking studies of tyrosol derivatives

Abstract

To find a potent α-glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the meta, ortho, or para position of the phenyl group have been synthesised via the Mitsunobu reaction, characterised by ¹H NMR, ¹³C NMR, ESI-MS and IR and evaluated for inhibition. The derivatives possessed varying degrees of in vitro inhibitory activity against α-glucosidase and a relationship between the structure and activity was subsequently established for all compounds. Two of these compounds with substituents at the para position showed significant inhibitory effects surpassing that of the control standard acarbose. Molecular docking studies performed to better understand the binding interactions between the enzyme and the two most active compounds showed substantial binding within the active site of α-glucosidase. Taken together, these results indicate that the position of the substituent plays a crucial role in this inhibition and may facilitate the development of new α-glucosidase inhibitors.

GRAPHICAL ABSTRACT

Keywords:

• tyrosol
• synthesis
• α-glucosidase
• structure activity relationship
• molecular docking

Acknowledgement

We thank Rosalie Tran, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work is supported by the Science and Technology Development Funds of Jilin Province (No. 20160520044JH) and the Science and Technology Projects of Administration of Traditional Chinese Medicine of Jilin Province (No. 2019145).