Identification of Potential New <i>Aedes aegypti</i> Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach

Identification of Potential New <i>Aedes aegypti</i> Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach

<i>Aedes aegypti</i> mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated...

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Bibliographic Details
Main Authors: Lúcio R. Lima, Ruan S. Bastos, Elenilze F. B. Ferreira, Rozires P. Leão, Pedro H. F. Araújo, Samuel S. da R. Pita, Humberto F. De Freitas, José M. Espejo-Román, Edla L. V. S. Dos Santos, Ryan da S. Ramos, Williams J. C. Macêdo, Cleydson B. R. Santos
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
juvenile hormone
piperidine derivatives
pharmacophore
ADME/Tox
docking
molecular dynamics
Online Access:https://www.mdpi.com/1422-0067/23/17/9927
Description
Summary:<i>Aedes aegypti</i> mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from <i>Piper nigrum</i>, has been used as a hit compound due to its larvicidal activity against <i>Aedes aegypti</i>. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0<sup>®</sup>), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to <i>holo</i> (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the <i>Aedes aegypti</i> mosquitoes.
ISSN:1661-6596
1422-0067

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