Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Pará, Rua Augusto Corrêa, 01, Belém, Pará 66075110, Brazil.
Laboratory of Modeling and Computational Chemistry, Department of Biological Sciences, Federal University of Amapá, Rod. Juscelino Kubitschek, Km 02, s/n, Macapá, Amapá 68902-280, Brazil.
Molecules. 2018 Oct 29;23(11):2801. doi: 10.3390/molecules23112801.
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.
分子的抗氧化活性是调节氧化还原平衡和降低氧化应激的一个重要因素。受氧化应激影响的细胞可能会发生遗传改变，导致结构变化，并促进慢性疾病（如癌症）的发生。我们进行了一项计算机模拟研究，以评估锌数据库中的两种分子的抗氧化潜力：ZINC08706191（Z91）和 ZINC08992920（Z20）。进行了分子对接、量子化学计算（HF/6-31G**）和 Pearson 相关分析。Z91 和 Z20 的分子对接结果表明，在三种测试酶（细胞色素 P450-CP450、髓过氧化物酶-MP 和 NADPH 氧化酶-NO）中，受体-配体相互作用的结合亲和力（BA）和抑制常数（Ki）值均低于对照分子（每种受体的 5-氟尿嘧啶-FLU、褪黑素-MEL 和右美沙芬-DEX）。分子描述符与 Ki 相关，并且在 CP450、MP 和 NO 受体中观察到很强的相关性。这些和其他结果证明了 Z91 和 Z20 具有显著的抗氧化能力，这可能表明它们在控制氧化应激方面具有进一步分析的潜力，并且可能作为抗氧化剂用于制药工业。
