Design, Synthesis, and Insecticidal Activity of Pyridino[1,2-a]pyrimidines Containing Indole Moeites at the 1-Position.
J Agric Food Chem
; 72(20): 11331-11340, 2024 May 22.
Article
in En
| MEDLINE
| ID: mdl-38721769
ABSTRACT
Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aphids
/
Pyrimidines
/
Drug Design
/
Molecular Docking Simulation
/
Indoles
/
Insecticides
Limits:
Animals
Language:
En
Journal:
J Agric Food Chem
Year:
2024
Document type:
Article
Country of publication: