Costa Norberto S, Lima Lúcio R, Cruz Jorddy N, Santos Igor V F, Silva Rai C, Maciel Alexandre A, Barros Elcimar S, Andrade Maracy L D S, Ramos Ryan S, Kimani Njogu M, Aragón-Muriel Alberto, Álvarez-Caballero Juan M, Campos Joaquín M, Santos Cleydson B R
Graduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapa 68902-280, AP, Brazil.
Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, Brazil.
Pharmaceuticals (Basel). 2025 Jun 13;18(6):888. doi: 10.3390/ph18060888.
Prostate cancer is the most common cancer in men, especially after the age of 50. It is a malignant disease that is increasing due to the increased life expectancy of the world population. Its development and progression are dependent on androgenic stimulation. This study aimed to identify potential inhibitors with anti-prostate cancer activity through the application of chemoinformatics tools, exploring the Princeton (1.2 million compounds) and Zinc Drug (175 million compounds) databases. The methodology used several computational techniques, such as ROCS (Rapid Chemical Structure Superposition) and EON (Electrostatic Potential Screening), predictions of pharmacokinetic and toxicological properties, molecular docking, synthetic accessibility, biological activity, and molecular dynamics. At the end of all these virtual screening steps, the study resulted in four promising potential candidates for the treatment of prostate cancer: the molecules ZINC34176694, ZINC03876158, ZINC04097308, and ZINC03977981, which exhibited all the desirable pharmacokinetic parameters (ADME/Tox) for a potential drug. Docking and molecular dynamics studies demonstrate stability and interaction with the androgen receptor of the selected compounds, showing them to be promising candidates for the development of new drugs.
前列腺癌是男性中最常见的癌症，尤其是在50岁之后。它是一种恶性疾病，由于世界人口预期寿命的增加而呈上升趋势。其发生和发展依赖于雄激素刺激。本研究旨在通过应用化学信息学工具，探索普林斯顿数据库（约120万种化合物）和锌药物数据库（约1.75亿种化合物），来确定具有抗前列腺癌活性的潜在抑制剂。该方法使用了多种计算技术，如ROCS（快速化学结构叠加）和EON（静电势筛选）、药代动力学和毒理学性质预测、分子对接、合成可及性、生物活性以及分子动力学。在所有这些虚拟筛选步骤结束时，该研究得到了四种有前景的前列腺癌治疗潜在候选物：分子ZINC34176694、ZINC03876158、ZINC04097308和ZINC03977981，它们展现出了作为潜在药物所需的所有药代动力学参数（ADME/Tox）。对接和分子动力学研究证明了所选化合物与雄激素受体的稳定性和相互作用，表明它们是开发新药的有前景的候选物。
