Improved application of natural forest product terpene for discovery of potential botanical fungicide

Abstract

The development of efficient terpenoid fungicides and exploration of its action mechanism is of great significance for the prevention and control of agricultural diseases. To confirm our previous findings on naturally occurring antifungal products with ecofriendly features, 40 terpene-based acyl-thiourea derivatives were synthesized and structurally characterized by 1H NMR, ESI-MS, elemental analysis and IR spectroscopy. Their inhibitory activities against several fungi, including Botrytis cinerea, Sclerotinia sclerotiorum and Thanatephorus cucumeris, were assessed by the growth rate method and the in vivo antifungal effects of these compounds against Thanatephorus cucumeris were performed evaluated using detached leaves. The majority of these compounds showed moderate to marked antifungal activities. Of all compounds, myrtenyl-based acylthiourea (8i) displayed more pronounced antifungal activity against Thanatephorus cucumeris (EC50 = 0.412 mg/L) compared with carbendazim (EC50 = 0.436 mg/L). In vivo antifungal of compound 8i efficiency against Thanatephorus cucumeris was also excellent. Treatment with 8i of Thanatephorus cucumeris resulted in significantly influenced morphology, markedly increased cell membrane permeability, and reduced ATP amounts and ATPase activity in comparison with untreated controls. A total of four descriptors linking structures and antifungal activities against Thanatephorus cucumeris were determined, including qSmax, HOMO-LUMO, log MS and qNmax, and employed to build a quantitative structure-activity relationship (QSAR) model (R2 = 0.9673). Preliminary structure-activity relationship (SAR) and QSAR assessments revealed that electronic and steric effects as well as energy differences of various molecules markedly affected antifungal effects. These findings provide novel insights into the modes of action of terpene-based acyl-thiourea derivatives, which could constitute potential substitutes for current fungicides or leads for novel antifungal agent development.