Institute of Biodiversity. Federal University of Western Pará, Santarém, Pará, Brazil.
Institute of Pharmaceutical Sciences. Federal University of Pará, 66075-110, Belém, Pará, Brazil.
Comput Biol Chem. 2019 Dec;83:107102. doi: 10.1016/j.compbiolchem.2019.107102. Epub 2019 Aug 14.
Cancer is one of the leading causes of death worldwide, and the number of patients has only increased each year, despite the considerable efforts and investments in scientific research. Since natural products (NPs) may serve as suitable sources for drug development, the cytotoxicity against cancer cells of 2221 compounds from the Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBE) was predicted using CDRUG algorithm. Molecular modeling, chemoinformatics, and chemometric tools were then used to analyze the structural and physicochemical properties of these compounds. We compared the positive NPs with FDA-approved anticancer drugs and predicted the molecular targets involved in the anticancer activity. In the present study, 46 families comprising potential anticancer compounds and at least 19 molecular targets involved in oncogenesis. To the best of our knowledge, this is the first large-scale study conducted to evaluate the potentiality of NPs sourced from Brazilian biodiversity as anticancer agents, using in silico approaches. Our results provided interesting insights about the mechanism of action of these compounds, and also suggested that their structural diversity may aid structure-based optimization strategies for developing novel drugs for cancer therapy.
癌症是全球主要死因之一，尽管在科学研究方面投入了大量的努力和资金，但患者人数每年仍在增加。由于天然产物（NPs）可能是药物开发的合适来源，因此使用 CDRUG 算法预测了来自生物测定、生态生理学和天然产物生物合成数据库（NuBBE）的 2221 种化合物对癌细胞的细胞毒性。然后，使用分子建模、化学信息学和化学计量学工具来分析这些化合物的结构和物理化学性质。我们将阳性 NPs 与 FDA 批准的抗癌药物进行比较，并预测了参与抗癌活性的分子靶标。在本研究中，有 46 个家族包含潜在的抗癌化合物和至少 19 个参与肿瘤发生的分子靶标。据我们所知，这是第一项使用计算机模拟方法评估源自巴西生物多样性的 NPs 作为抗癌剂的潜力的大规模研究。我们的结果提供了关于这些化合物作用机制的有趣见解，并表明它们的结构多样性可能有助于基于结构的优化策略，以开发用于癌症治疗的新型药物。
