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General Research Article

姜黄素类似物的设计、合成、药代动力学及体外抗癌活性评价

卷 31, 期 5, 2024

发表于: 15 June, 2023

页: [620 - 639] 页: 20

弟呕挨: 10.2174/0929867330666230428162720

价格: $65

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摘要

背景：作为我们发现植物基先导分子的一部分，我们提供了一个有用的工具，有助于姜黄素的鉴定、设计、优化、结构修饰和预测，以发现具有增强生物利用度、药理安全性和抗癌潜力的新型类似物。 方法：建立了定量构效关系(Quantitative structure-activity relationship, QSAR)和药效团作图模型，并将其进一步用于姜黄素类似物的设计、合成、药代动力学和体外抗癌活性评价。 结果：QSAR模型的活动-描述符关系准确度(r2)为84%，活动预测准确度(rcv2)为81%，外部集预测准确度为89%。QSAR研究表明，这五种化学描述符与抗癌活性显著相关。确定的重要药效团特征是一个氢键受体、一个疏水中心和一个负电离中心。该模型的预测能力是针对一组化学合成的姜黄素类似物进行评估。9个姜黄素类似物的IC50值在0.10 ~ 1.86 μg/mL之间。评估活性类似物的药代动力学依从性。通过对接研究，发现EGFR是合成的活性姜黄素类似物的潜在靶点。 结论：集成芯片设计，QSAR驱动的虚拟筛选，化学合成和体外实验评估可能导致从天然来源中早期发现新的和有前途的抗癌化合物。所建立的QSAR模型和共同药效团的产生被用作设计和预测工具来开发新的姜黄素类似物。这项研究可能有助于优化所研究化合物的治疗关系，为进一步的药物开发和潜在的安全性问题提供帮助。该研究可指导化合物的选择和设计新的活性化学支架或新的姜黄素系列组合文库。

关键词: QSAR，药效团，ADMET，姜黄素，药代动力学，抗癌，对接，药物设计。

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