克脑文盖尔加合物对幼虫的杀灭潜力：理论研究与验证

Larvicidal potential of Knoevenagel adducts against : theoretical study and validation.

作者信息

Abrantes Paloma G, Abrantes Poliana G, Magalhães Renata R, Silva Gildilayne M, Sousa Natália F, Scotti Marcus T, Leite Renan T, Francelino Jheison M C, Nunes Fabíola C, Vale Juliana A

机构信息

Departamento de Química, Universidade Federal da Paraíba - UFPB, João Pessoa, Brasil.

Laboratório de Quimioinformática, Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba - UFPB, João Pessoa, Brasil.

出版信息

Future Med Chem. 2025 May;17(9):999-1011. doi: 10.1080/17568919.2025.2498877. Epub 2025 May 5.

DOI:10.1080/17568919.2025.2498877

PMID:40323274

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12091929/

Abstract

AIM

This study investigated the larvicidal potential of Knoevenagel adducts against larvae to develop sustainable alternatives for controlling disease vectors like dengue.

METHODS

Larvicidal activity of Knoevenagel adducts (1a-l) was evaluated on fourth-stage larvae. Additional analyses included nitric oxide measurement, cell profiling, toxicity assessment, molecular docking, molecular dynamics simulation, and ADMET (Absorption, Distribution, Metabolism, and Toxicity) evaluation.

RESULTS

Compounds 1c and 1g showed high larvicidal efficacy, with LC values of 3.39 and 5.13 ppm. Hemolymph analysis revealed altered hemocyte composition, indicating an immune response, though nitric oxide levels remained unchanged. Molecular docking identified strong interactions between the FKBP12 enzyme (PDB: 3UQI) and Knoevenagel adducts. Compound 1g had the highest activity probability and binding affinity, while 1c showed strong interactions validated by biological assays. Molecular dynamics confirmed stable interactions of 1c and FKBP12, with both 1c and 1g displaying significant van der Waals contributions. ADMET analysis highlighted 1c as a less toxic compound, with minimal mutagenic risk, favorable pharmacokinetics, and high bioavailability.

CONCLUSIONS

Knoevenagel adducts 1c and 1g are promising candidates for effective, selective, and environmentally friendly larvicides.

摘要

目的

本研究调查了克脑文盖尔加合物对幼虫的杀幼虫潜力，以开发控制登革热等病媒的可持续替代方法。

方法

评估了克脑文盖尔加合物（1a - l）对四龄幼虫的杀幼虫活性。其他分析包括一氧化氮测量、细胞分析、毒性评估、分子对接、分子动力学模拟和ADMET（吸收、分布、代谢和毒性）评估。

结果

化合物1c和1g表现出高杀幼虫效力，LC值分别为3.39和5.13 ppm。血淋巴分析显示血细胞组成改变，表明存在免疫反应，尽管一氧化氮水平保持不变。分子对接确定了FKBP12酶（PDB：3UQI）与克脑文盖尔加合物之间的强相互作用。化合物1g具有最高的活性概率和结合亲和力，而1c通过生物学试验验证显示出强相互作用。分子动力学证实了1c与FKBP12的稳定相互作用，1c和1g均显示出显著的范德华贡献。ADMET分析突出显示1c是一种毒性较小的化合物，具有最小的致突变风险、良好的药代动力学和高生物利用度。