Tabassum Rukhsana, Dilshad Erum
Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology (CUST), Islamabad, Pakistan.
J Taibah Univ Med Sci. 2025 Feb 13;20(1):89-106. doi: 10.1016/j.jtumed.2025.01.006. eCollection 2025 Feb.
Because aberrant Rho GTPase signaling has been associated with multiple cancers, it was investigated as a potential target for liver cancer treatment drugs. The important medicinal plant , found in the Karakoram Mountains, is believed to contain polyphenols that inhibit RhoA protein, thus potentially eliciting effects against liver cancer.
Polyphenols were identified in the methanolic extract of with HPLC, then screened for their anticancer potential against the RhoA protein through molecular docking and molecular dynamic simulations. The RMSD and RMSF values for each selected compound were determined, and ADMET characteristics were analyzed.
The polyphenols gallic acid, salicylic acid, caffeic acid, kaempferol, rutin, quercetin, coumarin, ferulic acid, sinapic acid, HB acid, vanillic acid, and chlorogenic acid were found in the methanolic extract of . On the basis of Lipinski's rule of five, the Vina score, and the cavity size, we chose five ligands with favorable features for further research. Caffeic acid was the most promising compound, on the basis of favorable ADMET qualities, and the best docking score and MD simulation results.
Caffeic acid remained intact and bound the protein structure throughout the simulation run, thus demonstrating a robust interaction between the protein and ligand, and indicating a possible inhibitory effect. Therefore, this compound might have the greatest ability to inhibit the RhoA protein. Further research is required to examine caffeic acid as a potential medication option for future drug development.
由于异常的Rho GTPase信号传导与多种癌症相关，因此将其作为肝癌治疗药物的潜在靶点进行研究。在喀喇昆仑山脉发现的一种重要药用植物被认为含有抑制RhoA蛋白的多酚，因此可能对肝癌产生作用。
用高效液相色谱法在该植物的甲醇提取物中鉴定多酚，然后通过分子对接和分子动力学模拟筛选其对RhoA蛋白的抗癌潜力。测定每种选定化合物的均方根偏差（RMSD）和均方根波动（RMSF）值，并分析其药物代谢动力学（ADMET）特征。
在该植物的甲醇提取物中发现了没食子酸、水杨酸、咖啡酸、山奈酚、芦丁、槲皮素、香豆素、阿魏酸、芥子酸、HB酸、香草酸和绿原酸等多酚。根据Lipinski的五规则、Vina评分和腔大小，我们选择了五种具有良好特性的配体进行进一步研究。基于良好的ADMET性质、最佳对接分数和分子动力学模拟结果，咖啡酸是最有前景的化合物。
在整个模拟过程中，咖啡酸保持完整并与蛋白质结构结合，从而证明了蛋白质与配体之间有强大的相互作用，并表明可能有抑制作用。因此，该化合物可能具有最大的抑制RhoA蛋白的能力。需要进一步研究将咖啡酸作为未来药物开发的潜在药物选择。
