Design of potential anti-cancer agents as COX-2 inhibitors, using 3D-QSAR modeling, molecular docking, oral bioavailability proprieties, and molecular dynamics simulation

被引：14

作者：

Er-rajy, Mohammed ^{[1
,2
]}

El Fadili, Mohamed ^{[1
]}

Faris, Abdelmoujoud ^{[1
]}

Zarougui, Sara ^{[1
]}

Elhallaoui, Menana ^{[1
]}

机构：

[1] Sidi Mohamed Ben Abdellah Univ, Fac Sci Dhar El Mahraz, LIMAS Lab, Fes, Morocco

[2] Sidi Mohamed Ben Abdellah Univ, Dept Chem, Fes 3100, Morocco

来源：

ANTI-CANCER DRUGS | 2024年 / 35卷 / 02期

关键词：

3D-QSAR; COX-2; inhibitors; dynamic molecular; molecular docking; oral bioavailability; SIMILARITY INDEXES ANALYSIS; ANALOGS; QSAR; CYCLOOXYGENASE-2; EXPLORATION; DERIVATIVES; SELECTIVITY; BINDING;

D O I：

10.1097/CAD.0000000000001492

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Modeling the structural properties of novel morpholine-bearing 1, 5-diaryl-diazole derivatives as potent COX-2 inhibitor, two proposed models based on CoMFA and CoMSIA were evaluated by external and internal validation methods. Partial least squares analysis produced statistically significant models with Q2 values of 0.668 and 0.652 for CoMFA and CoMSIA, respectively, and also a significant non-validated correlation coefficient R-2 with values of 0.882 and 0.878 for CoMFA and CoMSIA, respectively. Both models met the requirements of Golbraikh and Tropsha, which means that both models are consistent with all validation techniques. Analysis of the CoMFA and CoMSIA contribution maps and molecular docking revealed that the R1 substituent has a very significant effect on their biological activity. The most active molecules were evaluated for their thermodynamic stability by performing MD simulations for 100 ns; it was revealed that the designed macromolecular ligand complex with 3LN1 protein exhibits a high degree of structural and conformational stability. Based on these results, we predicted newly designed compounds, which have acceptable oral bioavailability properties and would have high synthetic accessibility.

引用

页码：117 / 128

页数：12

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