Hydrazone modification of non-food natural product sclareolide as potential agents for plant disease

Abstract

Plant diseases and their drug resistance pose a serious threat to agricultural production. One way to solve this problem is to discover new and efficient botanical pesticides. Herein, a series of novel hydrazide-hydrazone-containing sesquiterpenoid derivatives were synthesized by simply modifying the structure of the non-food natural product sclareolide. The biological activity results illustrated that compared to ningnanmycin (39.2 μg/mL), compound Z28 had the highest antiviral activity against tobacco mosaic virus (TMV), and the concentration for 50% of maximal effect (EC50) of its inactivation activity was 38.7 μg/mL, followed by compound Z14 (40.6 μg/mL). Transmission electron microscopy (TEM) demonstrated that TMVs treated with compounds Z14 and Z28 were broken into rods of different lengths, and their external morphology was fragmented or even severely fragmented. Autodocking and molecular dynamics (MD) simulations indicated that compound Z28 had a strong affinity for tobacco mosaic virus coat protein (TMV-CP), with a higher binding energy of −8.25 kcal/mol compared to ningnanmycin (−6.79 kcal/mol). The preliminary mechanism revealed that compound Z28 can achieve an antiviral effect by targeting TMV-CP, rendering TMV unable to self-assemble and replicate, and might be a candidate for a novel plant antiviral agent. Furthermore, the curative and protective activities of compound Z22 (EC50 = 16.1 μg/mL) against rice bacterial blight were 51.3% and 50.8%, respectively. Its control effect was better than that of bismerthiazol (BT) and thiadiazole copper (TC), compound Z22 that can be optimized as an active molecule.

Keywords

• Sesquiterpenoid derivatives
• Hydrazide-hydrazone
• Antiviral activity
• Tobacco mosaic virus
• Preliminary mechanism