Virtual Screening, Synthesis, and Bioactivity Evaluation for the Discovery of β-N-acetyl-D-hexosaminidase Inhibitors.

Abstract

Molting is an essential insect developmental process, in which a variety of enzymes are involved. The inhibition of these enzymes affect normal insect growth and development and may even cause death. OfHex1, one of the β-N-acetyl-D-hexosaminidases, is a key enzyme involved in the molting process of the Asian corn borer (Ostrinia furnacalis), and is deemed a potential insecticidal target.Based on the crystal structure of OfHex1, virtual screening was carried out to obtain a novel class of OfHex1 inhibitors, of which, 28 compounds were subjected to bioactivity evaluation. The compound 3, N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen- -2-yl) benzamide, showed good inhibition against OfHex1 with a K value of 11.2 μM. Structure optimization and molecular docking were applied for the structure-activity relationship analysis. The results also showed that the cyano group of this compound was essential for the maintenance of its inhibitory activity against OfHex1. Additionally, the interaction between this compound and Trp490, Glu328, Tyr475 and Trp524 were important for the inhibitory activity.The advantages of the derivatives of 2-amino-4,5,6,7-tetrahydrobenzo [b]thiophene -3-carbonitrile, which were their simple chemical structures and easy synthesis, elect them to be developed further as potential OfHex1 inhibitors for pests control. This article is protected by copyright. All rights reserved.