Roburic acid represents a novel non-aromatic scaffold for multitarget insect chitinase inhibitor

Natural products capable of simultaneously inhibiting multiple insect chitinases represent promising candidates for the developing environmentally benign insecticides. Currently, the vast majority of known multitarget inhibitors possess conjugated planar cyclic rigid frameworks, while inhibitors with alternative scaffold remain largely unexplored. In this study, the terpenoid roburic acid is identified as a novel non-aromatic scaffold for multitarget inhibition of insect chitinases. Roburic acid exhibits submicromolar K i values of 0.51 ​μM against OfChtI and 0.48 ​μM against OfChi-h from Ostrinia furnacalis . Molecular docking analysis indicates that roburic acid binds within the substrate-binding cleft of chitinases via hydrophobic interactions. Insecticidal assays further reveal that roburic acid caused 85 ​% mortality in O. furnacalis larvae and achieved 95 ​% mortality in Plutella xylostella at 2 ​mM. These results establish roburic acid as a promising lead for insecticide development targeting the molting process and provide a novel non-aromatic scaffold for the discovery of multitarget chitinase inhibitors. Graphic Abstract. Roburic acid represents a novel non-aromatic scaffold for multitarget insect chitinase inhibitor and demonstrates high insecticidal activity. Roburic acid represents a novel non-aromatic scaffold for multitarget insect chitinase inhibitor and demonstrates high insecticidal activity. • The terpenoid roburic acid was identified for the first time as a multitarget inhibitor that suppressed insect chitinases. • The non-aromatic scaffold of roburic acid presents a novel avenue for the design of chitinase inhibitors. • Roburic acid, with submicromolar-level potency, demonstrated potent insecticidal activity against Lepidopteran larvae.