Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC50 values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 mu g/mL, respectively, whereas the LC50 value of MA was 659.34 mu g/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 mu g/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.

Automated summary

Many studies have found that matrine (MA) has various pharmacological activities and high prospects for use as a natural pesticide. In this study, 58 derivatives of MA were prepared and tested for their mosquitocidal activity. Compounds 4e and 4m showed good larvicidal activity against Aedes albopictus and also exhibited inhibitory activity against acetylcholinesterase.