Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson’s correlation for the construction of quantitative structure–activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R² = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964, Z-627, and Z-814, with their predicted pIC₅₀ (−log IC₅₀) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski’s rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.

Aedes aegypti 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 Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. 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^®), 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 holo (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 Aedes aegypti mosquitoes.

Os Líquidos Iônicos (LI) são solventes moleculares orgânicos que apresentam certas vantagens (propriedades químicas interessantes), como baixa pressão de vapor, o que significa que esses solventes permanecem na fase líquida em condições normais; eles também são sais orgânicos fundidos não inflamáveis, que permanecem estáveis em temperaturas mais elevadas do que os solventes convencionais. Nos últimos anos, o número de pesquisas envolvendo líquidos iônicos vem crescendo devido à sua utilização na indústria, seja em processos de extração, de reações de síntese, de catálise e/ou em processos eletroquímicos. Por conta da sua ampla utilidade, neste trabalho, foram utilizadas equações de estado cúbicas (van der Waals e Peng-Robinson) e não-cúbicas (Rackett-Soave e Rackett-Yamada) para calcular o peso específico do líquido iônico [bmim][PF6]. Os resultados obtidos foram comparados com dados experimentais e observou-se que nas condições de pressão e temperatura avaliadas, a equação de estado de Peng-Robinson apresentou melhores resultados que a equação de estado de van der Waals, porém, as equações de estado não-cúbicas apresentaram um erro menor do que as equações de estado cúbicas quando comparadas com os dados da literatura.