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

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.

Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism

“…The indomethacin structure is a non-selective inhibitor ( Mus musculus , PDB 4COX) and rofecoxib structure bound to human COX-2 ( Homo sapiens , PDB 5KIR) were used via AutoDock 4.2/Vina 1.1.2 (Scripps Research Ins., San Diego, CA, USA) by graphical interface Pyrx (version 0.8.30) with default parameters via the genetic algorithm, following the protocol described previously by Padilha et al (2016), Pereira et al (2018) and Costa et al (2018) [64,65,66]. The population size was 100, selection-pressure was 1.1, the number of operations was 10,000, the number of islands was 1, the niche size was 2, operator weights for migrate was 0, mutate was 100 and crossover was 100.…”

Computational Approaches for Drug Discovery

“…Molecular descriptors were correlated with Ki and strong correlations were observed for the CYP450, 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 [31]. Frau and collaborators employed an in-silico protocol to assess the reactivity behavior of the anticancer marine drugs, Soblidotin and Tasidotin based on the calculation of the global and local descriptors resulting from Chemical Reactivity Theory (CRT), also known as Conceptual DFT, for their consideration as a useful complement to approximations based on Molecular Docking.…”

In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity

“…One way to probe the ability of scoring functions is analyzing the best pose obtained through the program and the conformation of crystallographic ligand [30]. When root-mean-square deviation of atomic positions (RMSD) between them is less than 2 Å, the model achieves satisfactory solutions (conformational search and scoring functions), according to the literature data [31,32,33,34,35,36,37,38,39].…”

“…We have considered alerts of toxicity involving the human species and also classified it as plausible in mammals. It is considered that in addition to toxicity, DEREK can identify aspects related to carcinogenicity, mutagenicity, skin sensitization, irritation, teratogenicity and neurotoxicity [38,39,63].…”