Synthesis, Biological Evaluation and Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids against Phytopathogenic Fungi

Abstract

Natural stilbenes (especially resveratrol) play important roles in plant protection by acting as both constitutive and inducible defenses. However, their exogenous applications on crops as fungicidal agents are challenged by their oxidative degradation and limited availability. In this study, a new class of resveratrol-inspired oxadiazole-stilbene hybrids was synthesized via Wittig-Horner reaction. Bioassay results indicated that some of the compounds exhibited potent fungicidal activity against Botrytis cinerea in vitro. Among these stilbene hybrids, compounds 11 showed promising inhibitory activity with the EC50 value of 144.6 μg/mL, which was superior to that of resveratrol (315.6 μg/mL). Remarkably, the considerably abnormal mycelial morphology was observed in the presence of compound 11. The inhibitory profile was further proposed by homology modeling and molecular docking studies, which showed the possible interaction of resveratrol and oxadiazole-stilbene hybrids with the cytochrome P450-dependent sterol 14α-demethylase from B. cinerea (BcCYP51) for the first time. Taken together, these results would provide new insights into the fungicidal mechanism of stilbenes, as well as an important clue for biology-oriented synthesis of stilbene hybrids with improved bioactivity against plant pathogenic fungi in crop protection.

Synthesis and antifungal activities of novel thiophene‐based stilbene derivatives bearing an 1,3,4‐oxadiazole unit

“…Inner vacuoles were found in 5j ‐treated hyphae, whereas this was rarely seen in the control mycelium. Similar results were observed in our previous study in which the mycelial cell membrane system was significantly damaged by the membrane permeability assay …”

“…In particular, the inhibition rates of compounds 5h and 5j at 200 µ g mL −1 were 47.5% and 48.4%, respectively, similar to that of fluopyram (47.1%). Interestingly, all the target compounds in this study containing a thiophene moiety had EC 50 values < 200 µ g mL −1 against B. cinerea , whereas only one fluorine‐containing compound displayed relative antifungal activity with an EC 50 value < 200 µ g mL −1 in our previously report . The results indicated that introduction of a thiophene moiety was favorable for antifungal activities.…”

“…Interestingly, all the target compounds in this study containing a thiophene moiety had EC 50 values < 200 μg mL −1 wileyonlinelibrary.com/journal/ps against B. cinerea, whereas only one fluorine-containing compound displayed relative antifungal activity with an EC 50 value < 200 μg mL −1 in our previously report. 17 The results indicated that introduction of a thiophene moiety was favorable for antifungal activities.…”

“…Similar results were observed in our previous study in which the mycelial cell membrane system was significantly damaged by the membrane permeability assay. 17,39…”

Synthesis of Stilbene and Chalcone Inhibitors of Influenza A Virus by SBA-15 Supported Hoveyda-Grubbs Metathesis

“…Thus, new antiviral agents are required to efficiently inhibit influenza viruses. Stilbenes and chalcones are natural compounds characterized by several biological activities, including defense mechanisms in plants [7], fungicidal activity [8], antioxidant [9], chemopreventive [10] and cardioprotective effects [11], atherosclerosis [12], neurodegeneration [13], obesity [14] and diabetes control [15], and antimicrobial [16] and anticancer activities [17]. Analysis and reviews of the role of stilbenes in viral therapy [18], such as the inhibition of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2) [19], respiratory syncytial (RSV) [20], human immunodeficiency (HIV) [21], varicella-zoster [22], and hepatitis C viruses [23], have been reported, including the activity against Influenza viruses [24].…”