阿魏酸衍生物与 FGFR1 的对接研究、ADME 预测和 QSPR 分析

IF 0.5 Q4 EDUCATION, SCIENTIFIC DISCIPLINES

Pharmacy Education Pub Date : 2024-05-01 DOI:10.46542/pe.2024.243.178184

Darwin Riyan Ramadhan, J. Ekowati, Denayu Pebrianti, Farrah Yulian Listyandi, N. Diyah, M. Adrianto, Deepakkumar Mishra

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引用次数: 0

摘要

背景：FGFR-1 是一种血管生成受体，在癌症生长途径中发挥着巨大作用。抑制血管生成的药物有很大的副作用。因此，仍有必要研究发现抗血管生成药物，以实现身心健康：通过与 FGFR1 的对接研究，从阿魏酸（FA）中设计新型抗血管生成候选药物，预测其 ADME 谱，并通过 QSPR 分析找出其药代动力学特性的结构关系：Autodock工具进行了对接研究。采用 SwissADME 进行 ADME 预测。结果对接结果表明，FA-8 和 FA-18 的自由能结合率、抑制常数和胃肠道吸收率最低。QSPR 分析得到了方程模型：Log HIA = 0,018 Log P2 + 0,069 Log P + 0,020 CMR + 0,001 Etotal + 1,771 n = 24，相关系数（r）= 0.621，P 值= 0.046，F 值= 2.975：用酯类取代酚基上的 FA 可提高活性和 ADME 特征。高对数 P、摩尔折射率（CMR）和电子因子（Etotal）支持了预测的生物利用度。建议增加亲脂性以获得更好的药代动力学特性。

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Docking study of ferulic acid derivates on FGFR1, ADME prediction, and QSPR analysis

Background: FGFR-1 is an angiogenic receptor that plays a huge role in the cancer growth pathway. Angiogenesis inhibitory drugs released have significant side effects. Therefore, research into discovering anti-angiogenic agents to achieve good health and well-being is still necessary. Objective: To design the novel anti-angiogenic candidates from ferulic acid (FA) by docking study on FGFR1, to predict the ADME profile, and to find out the structural relationship of their pharmacokinetic properties as QSPR analysis. Method: Autodock Tools performed a docking study. ADME prediction was conducted using SwissADME. The MLR approach determined the QSPR model. Result: The docking results showed that FA-8 and FA-18 had the lowest free energy binding, inhibition constant, and GI absorption. The QSPR analysis obtained the equation model: Log HIA = 0,018 Log P2 + 0,069 Log P + 0,020 CMR + 0,001 Etotal + 1,771 with n = 24, correlation coefficient (r)= 0.621, p-value= 0.046 and F-value= 2.975. Conclusion: Modifying FA on the phenolic moiety replaced by an ester increased the activity and ADME profile. The predicted bioavailability was supported by high Log P, molar refractivity (CMR), and electronic factor (Etotal). It is recommended that lipophilicity be increased to achieve better pharmacokinetic properties.

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来源期刊

Pharmacy Education EDUCATION, SCIENTIFIC DISCIPLINES-

CiteScore

0.80

自引率

20.00%

发文量

174

期刊介绍： Pharmacy Education journal provides a research, development and evaluation forum for communication between academic teachers, researchers and practitioners in professional and pharmacy education, with an emphasis on new and established teaching and learning methods, new curriculum and syllabus directions, educational outcomes, guidance on structuring courses and assessing achievement, and workforce development. It is a peer-reviewed online open access platform for the dissemination of new ideas in professional pharmacy education and workforce development. Pharmacy Education supports Open Access (OA): free, unrestricted online access to research outputs. Readers are able to access the Journal and individual published articles for free - there are no subscription fees or ''pay per view'' charges. Authors wishing to publish their work in Pharmacy Education do so without incurring any financial costs.