Preparation, Agricultural Bioactivity Evaluation, Structure–Activity Relationships Estimation, and Molecular Docking of Some Quinazoline Compounds

Abstract

Quinazoline compounds have gained significant attention in the fields of agriculture and chemistry due to their diverse activities. In this study, we focused on a series of quinazoline derivatives (<b>4a-l</b>). The objectives involved multiple aspects, including preparation, evaluation of their agricultural bioactivity against the maize aphid (<i>Rhopalosiphum maidis</i>), estimation of the structure-activity relationships (SAR), and conducting molecular docking analysis. The results of the agricultural bioactivities revealed that compound (<b>4b</b>) possesses the highest insecticidal activity, and the other compounds have good potential as insecticidal agents. We conducted the SARs and also molecular docking investigation to elucidate the binding modes and interactions of these compounds with target proteins relevant to the agricultural bioactivity. The docking results provided valuable information on the binding affinities and molecular interactions, aiding in the rationalization of the observed bioactivity trends. The enzyme, acetylcholinesterase (AChE), was docked with the 12 synthetic compounds (<b>4a-l</b>). Among these compounds, (<b>4b</b>), (<b>4i</b>), and (<b>4e</b>)exhibited the highest binding affinity, with docking scores (S) of -7.96, -7.83, and -7.73 kcal/mol, respectively. They were followed by compounds (<b>4d</b>) (S = -7.57 kcal/mol), (<b>4c</b>) (S = -7.53 kcal/mol), (<b>4g</b>) (S = -7.34 kcal/mol), (<b>4f</b>) (S = -7.23 kcal/mol), (<b>4h</b>) (S = -7.14 kcal/mol), (<b>4k</b>) (S = -6.61 kcal/mol), (<b>4j</b>) (S = -6.57 kcal/mol), (<b>4a</b>) (S = -6.28 kcal/mol), and finally (<b>4l</b>) (S = -6.01 kcal/mol). These compounds were shown to have a variety of binding interactions within the 2ACE active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have AChE-inhibitory capabilities and, hence, may be used for AChE-targeting development. Also, the findings in this study highlight the potential of these compounds as agricultural agents and provide valuable insights for the design and development of some quinazoline derivatives with enhanced bioactivity for crop protection.