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. 2018 Oct 29;23(11):2801.
doi: 10.3390/molecules23112801.

An In Silico Study of the Antioxidant Ability for Two Caffeine Analogs Using Molecular Docking and Quantum Chemical Methods

Josivan da Silva Costa  1   2   3 , Ryan da Silva Ramos  4   5 , Karina da Silva Lopes Costa  6 , Davi do Socorro Barros Brasil  7 , Carlos Henrique Tomich de Paula da Silva  8 , Elenilze Figueiredo Batista Ferreira  9 , Rosivaldo Dos Santos Borges  10 , Joaquín María Campos  11 , Williams Jorge da Cruz Macêdo  12   13 , Cleydson Breno Rodrigues Dos Santos  14   15   16
Affiliations

An In Silico Study of the Antioxidant Ability for Two Caffeine Analogs Using Molecular Docking and Quantum Chemical Methods

Josivan da Silva Costa et al. Molecules. .

Abstract

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of the oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. We have performed an in silico study to evaluate the antioxidant potential of two molecules of the zinc database: ZINC08706191 (Z91) and ZINC08992920 (Z20). Molecular docking, quantum chemical calculations (HF/6-31G**) and Pearson's correlation have been performed. Molecular docking results of Z91 and Z20 showed both the lower binding affinity (BA) and inhibition constant (Ki) values for the receptor-ligand interactions in the three tested enzymes (cytochrome P450-CP450, myeloperoxidase-MP and NADPH oxidase-NO) than the control molecules (5-fluorouracil-FLU, melatonin-MEL and dextromethorphan-DEX, for each receptor respectively). Molecular descriptors were correlated with Ki and strong correlations were observed for the CP450, MP and NO receptors. These and other results attest the significant antioxidant ability of Z91 and Z20, that may be indicated for further analyses in relation to the control of oxidative stress and as possible antioxidant agents to be used in the pharmaceutical industry.

Keywords: antioxidant potential; binding free energy; free radicals; molecular descriptors; molecular docking; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Data obtained in the validation of the molecular docking protocols for the receptors cytochrome P450 (CP450), lypoxygenase (LO), myeloperoxidase (MP), NADPH oxidase (NO) and xanthine oxidase (XO).
Figure 2
Figure 2
Binding free energy values resulting from the molecular docking between the molecules and receptors evaluated. Control molecules for CP450, LO, MP, NO and XO were 5-fluorouracil (FLU), zileuton (ZIL), melatonin (MEL), dextromethorphan (DEX) and febuxostat (FEB), respectively.
Figure 3
Figure 3
Binding affinity provided by AutoDock/Vina software of the tested molecules (Z20 and Z91). Control 1/Control 2 molecules for CP450, LO, MP, NO and XO were FLU/S-warfarin, ZIL/protocatechuic acid, MEL/N-acetyl-D-glucosamine, DEX/adenosine-5’-diphosphate and FEB/hypoxanthine, respectively.
Figure 4
Figure 4
Interactions of the tested molecules (Z20 and Z91) and control (FLU) with the CP450 receptor. In A, interactions common to the three ligands (blue), two ligands (green) and interactions presented by a single ligand (yellow) are presented. formula image Hydrogen bond (A); formula image carbon-hydrogen bond (B); formula image pi-sigma (C); formula image pi-alkyl (D); formula image alkyl (E).
Figure 5
Figure 5
Interactions of the tested molecules (Z20 and Z91) and control (MEL) with the MP receptor. In A, interactions common to the three ligands (blue) and two ligands (green). formula image Hydrogen bond (A); formula image carbon-hydrogen bond (B); formula image pi-sigma (C); formula image pi-alkyl (D); formula image alkyl (E).
Figure 6
Figure 6
Interactions of the tested molecules (Z20 and Z91) and control (DEX) with the NO receptor. In A, interactions common to the three ligands (blue), two ligands (green) and interactions presented by a single ligand (yellow) are presented. formula image Hydrogen bond (A); formula image carbon-hydrogen bond (B); formula image pi-sigma (C); formula image pi-alkyl (D); formula image akyl (E).
See this image and copyright information in PMC

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