Design, synthesis, and antifungal activity of novel cyanoacrylate derivatives containing a naphthalene moiety as potential myosin-5 inhibitor

Abstract

In search of innovative antifungal solutions for the control of plant diseases, a series of cyanoacrylate derivatives containing naphthalene groups were designed and synthesized, and their inhibition activity against four plant pathogenic fungi was evaluated. The results of in vitro bioassay revealed that some target compounds possessed obvious antifungal effect against Fusarium graminearum. As the most prominent one, compound A2 showed a inhibition rate of 98.46 % at 10 µg/mL and an EC50 value of 0.26 µg/mL, which was close to that of the positive control phenamacril (with a inhibition rate of 100 % at 10 µg/mL and EC50 value of 0.14 µg/mL). The compound A2 also markedly inhibited the growth of F. graminearum inoculated on rice leaves at 200 μg/mL with the protective and curative efficiencies of 89.03 % and 90.91 %, respectively, which were close to that of the positive control phenamacril (with the protective and curative efficiencies of 94.54 % and 96.36 %, respectively). The observation under scanning electron microscopy and measurement of relative conductivity revealed that compound A2 caused the hyphal surface become shrunken and rough, and made the cell membrane permeability increased. Molecular docking and molecular dynamics simulation analyses showed that compound A2 interacted with the key residues in the active site of myosin-5 in a similar mode as phenamacril. These results suggested that target compounds were potential myosin-5 inhibitors, they could serve as the lead compounds for further structural optimization to develop new fungicides against F. graminearum.

Keywords

• Cyanoacrylate derivatives
• Naphthalene
• Synthesis
• Antifungal activity
• F. graminearum