Carbonyl-bridged trifluoromethyl pyridine derivatives for pest control and mechanistic investigations

Trifluoromethyl pyridine ( TFMP ) motif is commonly discovered in structures of active pharmaceuticals. Flonicamid, characterized by the TFMP moiety, is well known as a prodrug in the knockdown of pests. The azobenzene-modified TFMP derivatives have been previously reported with excellent insecticidal activities. Herein, twenty-one TFMP derivatives were designed by the introduction of carbonyl-bridged aryl groups and synthesized via a one-step synthesis using Flonicamid as the starting material. The structure-activity relationships of these compounds were well analyzed and discussed. A molecular docking study and calcium ion concentration analysis indicated that compound FC13 could have interacted with the nicotinamidase enzyme, which further influenced the Ca 2+ influx. • Further deazotization of the previously reported high-active azobenzene-modified Flonicamid was performed in this paper. • Structure-activity relationships of the new carbonyl-bridged trifluoromethyl pyridine derivatives were analyzed and discussed to guide prodrug optimization. • Compound FC13 could influence the Ca 2+ influx, indirectly revealing its interaction with the nicotinamidase enzyme.