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J Mol Model ; 28(1): 1, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862566


Vitamin C or ascorbic acid is an indispensable micronutrient for human health found principally on citrus species such as lemon and orange fruits and vegetables. It was involved in the production of proteins such as collagen. Its biochemical mechanism is related to its antioxidant capacity; however, its function at the cellular level is still unclear. Several theoretical studies about antioxidant and redox mechanisms for ascorbic acid were suggested; however, no derivative was proposed. Thereby, an electronic study of antioxidant capacity for ascorbic acid derivatives was performed using theoretical chemistry at the DFT/ B3LYP/6-311 + + (2d,2p) level of theory. Simplified derivatives show that enol hydroxyls are more important than any other functional group. The vicinal enolic hydroxyl on ß position is more important for antioxidant capacity of ascorbic than hydroxyl on α position. According to our molecular modifications, the keto-alkene compound showed the best values when compared to ascorbic acid in some molecular characteristics. No lactone derivatives have superior application potential as antioxidant when compared with ascorbic acid. Several structures are possible to be proposed and were related to spin density contributions and the increase of chemical stability. New promising structural derivatives related to ascorbic acid can be developed in the future.

Molecules ; 25(5)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32164183


Adenosine Receptor Type 2A (A2AAR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A2AAR. For the search for A2AAR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC50 = 7.54407; ZINC04257548 pEC50 = 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan®), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A2AAR.

Receptores A2 de Adenosina/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Humanos , Ligantes , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade
Molecules ; 24(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609687


A drug design for safer phenylbutazone was been explored by reactivity and docking studies involving single electron transfer mechanism, as well as toxicological predictions. Several approaches about its structural properties were performed through quantum chemistry calculations at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and ionization potential were associated to electron donation capacity. The spin densities contribution showed a preferential hydroxylation at the para-positions of phenyl ring when compared to other positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than alkyl hydroxylation. Docking studies indicate that six structures 1, 7, 8 and 13⁻15 have potential for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed are potentially more active as well safer than phenylbutazone and only structures 8 and 13⁻15 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.

Fenilbutazona/química , Fenilbutazona/farmacologia , Descoberta de Drogas/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fenilbutazona/efeitos adversos , Fenilbutazona/toxicidade , Relação Estrutura-Atividade