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Evaluation of the ADME, toxicological analysis and molecular docking studies of the anacardic acid derivatives with potential antibacterial effects against staphylococcus aureus


Journal of Analytical & Pharmaceutical Research
Jacilene Silva,1 Matheus Nunes da Rocha,2 Emanuelle Machado Marinho,3 Márcia Machado Marinho,4 Emmanuel Silva Marinho,2 Hélcio Silva dos Santos1,5,6

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Abstract

Sulfonamide of anacardic acid derivatives (AAD) are promising bioactive compounds and have reported antibacterial biological activity. However, until now its physicochemical and pharmacokinetic properties have not been reported. In this study, the series of synthetic AAD compounds were subjected to pharmacokinetic and drug-like predictions from the absorption, distribution, metabolism and excretion (ADME) models. To predict the “druglike” physicochemical properties of a series of synthetic compounds, computational techniques and a series of criteria based on Lipinski and Veber rules are used. In the results, it was possible to observe that the AAD6 derivative has the lowest oral bioavailability. Therefore, the AAD1 compound has the highest intestinal absorption and is easily eliminated because it does not inhibit CYP450 1A2, 2D6 and 3A4, while the AAD2 compound executes its antibacterial active ingredient with the lowest toxicological risk of this test. From the results of the antimicrobial activity of AADs with Staphylococcus aureus, in silico studies of ADME and toxicity analyses, four AAD derivatives (2, 8, 11 and 12) were selected for pharmacodynamic analysis, in which the interactions of the selected AADs were evaluated using the in silico molecular docking method. The results obtained showed that AAD12 presented the best affinity energy values with the three target receptors used (Penicillin Binding Protein, Isoleucyl-tRNA synthetase and DNA Gyrase). The results also showed that derivatives 8, 11 and 12 showed interactions with residues from the catalytic site of Isoleucyl-tRNA synthetase, and can be considered potential antibacterial agents against Staphylococcus aureus.

Keywords

virtual screening, anacardic acid derivatives, staphylococcus aureus, ADME, molecular docking

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