Identification of Potential Insect Growth Inhibitor against Aedes aegypti: A Bioinformatics Approach

Abstract

Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of dengue have been reported in recent years, showing significant growth. The best way to manage diseases transmitted by Aedes aegypti is to control the vector with insecticides, which have already been shown to be toxic to humans; moreover, insects have developed resistance. Thus, the development of new insecticides is considered an emergency. One way to achieve this goal is to apply computational methods based on ligands and target information. In this study, sixteen compounds with acceptable insecticidal activities, with 100% larvicidal activity at low concentrations (2.0 to 0.001 mg·L−1), were selected from the literature. These compounds were used to build up and validate pharmacophore models. Pharmacophore model 6 (AUC = 0.78; BEDROC = 0.6) was used to filter 4793 compounds from the subset of lead-like compounds from the ZINC database; 4142 compounds (dG < 0 kcal/mol) were then aligned to the active site of the juvenile hormone receptor Aedes aegypti (PDB: 5V13), 2240 compounds (LE < −0.40 kcal/mol) were prioritized for molecular docking from the construction of a chitin deacetylase model of Aedes aegypti by the homology modeling of the Bombyx mori species (PDB: 5ZNT), which aligned 1959 compounds (dG < 0 kcal/mol), and 20 compounds (LE < −0.4 kcal/mol) were predicted for pharmacokinetic and toxicological prediction in silico (Preadmet, SwissADMET, and eMolTox programs). Finally, the theoretical routes of compounds M01, M02, M03, M04, and M05 were proposed. Compounds M01–M05 were selected, showing significant differences in pharmacokinetic and toxicological parameters in relation to positive controls and interaction with catalytic residues among key protein sites reported in the literature. For this reason, the molecules investigated here are dual inhibitors of the enzymes chitin synthase and juvenile hormonal protein from insects and humans, characterizing them as potential insecticides against the Aedes aegypti mosquito.

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

“…The inhibitory activity of 1-(3-nitropyridin-2-yl)piperazine derivatives ( 5a-o; 7a-k ) was assessed in vitro against urease with minor modifications using the indophenol method ( Al Azzam et al, 2022 ; Da Costa et al, 2022 ). At first, 1 mM solution of a test compound was prepared in 10% DMSO followed by the preparation of the reaction mixture.…”

“…Furthermore, GUSAR ( http://www.way2drug.com/gusar/acutoxpredict.html , accessed on 11 September 2023) was used to evaluate the optimal route of administration of potent inhibitors to rats for in vivo studies in the future based on lethal dose 50 (LD 50 ) values ( Al Azzam et al, 2022 ). Similarly, eMolTox functions as an online platform designed to forecast the possible toxicological effects linked to the molecular configuration of a compound using an aggregate predictor method ( Da Costa et al, 2022 ).…”

Probing the Interaction between Isoflucypram Fungicides and Human Serum Albumin: Multiple Spectroscopic and Molecular Modeling Investigations

“…Their use has led to an increasing concern about their potential adverse effects on human health and the environment [2]. Toxicity assessments for humans are essential for any pesticide [3,4]. Isoflucypram (Figure 1), the first representative of a newly installed subclass of SDHIs (succinate dehydrogenase inhibitors) within the FRAC (Fungicide Resistance Action Committee) family, has shown remarkable and long-lasting efficacy against major foliar diseases in cereals, as reported by Desbordes et al [5].…”