Piperonyl-Tethered Rhodanine Derivatives Potently Inhibit Chitinolytic Enzymes of .

Insect pest chitinases are potential target for developing new insect growth regulators. Piperine was found first to inhibit the insect chitinase (Chi-h) from (Asian corn borer) in this work, except for previously reported ChtI. Novel piperonyl-tethered rhodanine derivatives - were rationally designed with piperine as lead and synthesized by introducing a unique rhodanine moiety into the piperine scaffold based on the similar binding cavity of ChtI and Chi-h. Compared to piperine, compounds - showed approximately 100- to 400-fold or 110- to 210-fold higher inhibitory capacity against two chitinases, respectively. Molecular mechanism studies indicated that π interactions are crucial for improving inhibitory activity against two chitinases due to the introduction of the conjugated rhodanine ring. Moreover, compounds - could dramatically inhibit the growth and development of larvae by activity evaluation. This study provides novel piperonyl-tethered rhodanine derivatives inhibiting dual chitinases as insect growth regulator candidates.