Design of acyl salicylic acid derivates as COX-1 inhibitors using QSAR approach, molecular docking and QSPR analysis

Pub Date : 2024-05-01 DOI:10.46542/pe.2024.243.8894
N. Diyah, Dhea Ananda Ainurrizma, Denayu Pebrianti
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Abstract

Background: Acetylsalicylic acid (aspirin), widely used as an antiplatelet agent, is more likely to inhibit COX-1. Along with discovering the cardioprotective role of COX-1 in controlling platelet aggregation, it is important to develop a selective COX-1 inhibitor. Objective: This study aims to design acyl salicylic acid derivatives intended as COX-1 inhibitors. Method: Fourteen derivatives (AcS1-14) were subjected to a quantitative structure-activity relationship (QSAR) study, and 31 QSAR models were obtained using multiple linear regression (MLR) analysis. Molecular docking was performed on COX-1 (PDB. 1PTH) using the Molecular Orbital Environment (MOE) program ver2022.02, and QSPR analysis was conducted to ascertain the contribution of physicochemical descriptors to the free energy score (S) of ligand-receptor complexes. Results: The QSAR-Hansch model predicted hydrophobicity (LogP) and molecular energy (Etotal) and contributed to pain inhibitory action. All derivatives displayed higher in silico affinity than aspirin (S= -4.33±0.00 kcal/mol), and compound AcS7 afforded the highest (S= -5.32 kcal/mol). In QSPR, Etotal also revealed a positive contribution to the affinity. AcS1, AcS2, AcS5, AcS7, and AcS8 expressed higher drug-like properties than aspirin. Conclusion: Derivatives with optimum hydrophobicity and high energy would generate potent COX-1 inhibition. The five selected compounds were recommended to be developed as drug candidates for COX-1 inhibitors.
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利用 QSAR 方法、分子对接和 QSPR 分析设计作为 COX-1 抑制剂的酰基水杨酸衍生物
背景:乙酰水杨酸(阿司匹林)作为一种抗血小板药物被广泛使用,它更有可能抑制 COX-1。在发现 COX-1 在控制血小板聚集中的心脏保护作用的同时,开发一种选择性 COX-1 抑制剂也非常重要:本研究旨在设计可作为 COX-1 抑制剂的酰基水杨酸衍生物:对 14 种衍生物(AcS1-14)进行了定量结构-活性关系(QSAR)研究,并通过多元线性回归(MLR)分析获得了 31 个 QSAR 模型。使用分子轨道环境(MOE)程序 ver2022.02 对 COX-1(PDB.1PTH)进行了分子对接,并进行了 QSPR 分析以确定理化描述因子对配体-受体复合物自由能得分(S)的贡献:结果:QSAR-Hansch 模型预测了疏水性(LogP)和分子能(Etotal),并认为它们对止痛作用有贡献。所有衍生物的硅亲和力均高于阿司匹林(S= -4.33±0.00 kcal/mol),其中化合物 AcS7 的亲和力最高(S= -5.32 kcal/mol)。在 QSPR 中,Etotal 也显示出对亲和力的积极贡献。与阿司匹林相比,AcS1、AcS2、AcS5、AcS7 和 AcS8 具有更高的类药物特性:结论:具有最佳疏水性和高能量的衍生物将产生强效的 COX-1 抑制作用。结论:具有最佳疏水性和高能量的衍生物可产生强效的 COX-1 抑制作用,建议将所选的五个化合物开发为 COX-1 抑制剂的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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