Introduction: Inhibitors of topoisomerases, essential regulators of cancer development, are promising as cancer treatments. These enzymes regulate DNA topology and eliminate topological constraints during various biological processes, including replication, transcription, and recombination. Nature has continually offered scientists pathways to explore the development of new drugs. Indeed, since ancient times, various plant extracts have been utilized in treating multiple pathologies. Objective: It’s intriguing to diversify the therapeutic classes of natural topoisomerase 1 inhibitors. We aimed to explore the relationship between the toxicity of certain medicinal plants in North Africa and their anti-topoisomerase 1 enzyme activity. This investigation aims to discover potentially valuable compounds for fighting cancer by inhibiting the Topo1 enzyme, enriching the anticancer therapeutic class. Methods: This study has conducted a virtual screening of the African Natural Products Database to identify new scaffolds as topoisomerase 1 inhibitors. Molecular docking as a structure-based drug design approach was selected as one of the best approaches, and the complex code ID: 1K4T was used for this purpose. Results and Discussion: The molecular docking of more than 5790 natural products extracted from this database was docked into the binding site of the above-cited complex using the Modlock optimizer and Moldock score as search and scoring function algorithms, respectively. The top-ranked compounds have been assessed, analyzed, and compared to Topotecan and Irinotecan as reference ligands and drugs. Conclusion: Consequently, the seven natural products have shown a strong affinity to topoisomerase 1 and DNA. They establish a clear link between topoisomerase 1 inhibition and the anticancer activity of their corresponding plant extracts. Therefore, these hits are promising and serve as a base for further development of new topoisomerase 1 inhibitors.

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基于计算机结构的非洲天然产品中潜在抗癌生物活性天然成分的筛选

简介：拓扑异构酶抑制剂是癌症发展的重要调节剂，作为癌症治疗方法很有前景。这些酶调节 DNA 拓扑并消除各种生物过程（包括复制、转录和重组）中的拓扑限制。大自然不断为科学家提供探索新药开发的途径。事实上，自古以来，各种植物提取物就被用来治疗多种病症。目的：使天然拓扑异构酶 1 抑制剂的治疗类别多样化是很有趣的。我们旨在探讨北非某些药用植物的毒性与其抗拓扑异构酶 1 酶活性之间的关系。本研究旨在通过抑制Topo1酶来发现潜在有价值的抗癌化合物，丰富抗癌治疗类别。方法：本研究对非洲天然产物数据库进行了虚拟筛选，以确定作为拓扑异构酶 1 抑制剂的新支架。分子对接作为基于结构的药物设计方法被选为最佳方法之一，并且使用复杂代码ID：1K4T用于此目的。结果与讨论：使用 Modlock 优化器和 Moldock 评分分别作为搜索和评分函数算法，将从该数据库中提取的 5790 多种天然产物的分子对接对接到上述复合物的结合位点。对排名靠前的化合物进行了评估、分析，并与作为参考配体和药物的拓扑替康和伊立替康进行了比较。结论：因此，这七种天然产物对拓扑异构酶1和DNA表现出很强的亲和力。他们在拓扑异构酶 1 抑制与其相应植物提取物的抗癌活性之间建立了明确的联系。因此，这些成果具有广阔的前景，并可作为进一步开发新型拓扑异构酶 1 抑制剂的基础。