PDF(Pubmed)
Abstract：
Combination therapy and multitarget drugs have recently attracted much attention as promising tools to fight against many challenging diseases and, thus, represent a new research focus area. The aim of the current project was to screen multitarget compounds and to study their individual and combined effects on acetaminophen-induced liver injury. In this study, 2 of the best hepatoprotective multitargeting compounds were selected from a pool of 40 major compounds present in Curcuma longa and Cinnamomum zeylanicum by using molecular docking, ADMET profiling, and Pfizer\'s rule of five. The two selected compounds, quercetin and curcumin, showed a high binding affinity for the CYP2E1 enzyme, MAPK, and TLR4 receptors that contribute to liver injury. The candidates caused the decreased viability of cancer cell lines (HepG2 and Huh7) but showed no effect on a normal cell line (Vero). Examination of biochemical parameters (ALT, AST, ALP, and bilirubin) showed the hepatoprotective effect of the candidate drugs in comparison with the control group, which was confirmed by histological findings. Taken together, quercetin and curcumin not only satisfied the drug-like assessment criterion and proved to be multitargeting by preventing liver damage but also showed anticancer activities.
摘要：
联合治疗和多靶点药物最近吸引了很多关注作为有前途的工具，以对抗许多具有挑战性的疾病，因此，代表了一个新的研究重点领域。当前项目的目的是筛选多靶标化合物，并研究它们对对乙酰氨基酚诱导的肝损伤的个体和联合作用。在这项研究中,通过使用分子对接，从姜黄和Cinnamomumzeylanicum中存在的40种主要化合物中选择了2种最佳的肝保护性多靶向化合物，ADMET分析，和辉瑞的第五条规则。选定的两种化合物，槲皮素和姜黄素,显示对CYP2E1酶的高结合亲和力，MAPK,和导致肝损伤的TLR4受体。候选物使癌细胞系(HepG2和Huh7)的活力降低,但对正常细胞系(Vero)没有影响。生化参数检查（ALT，AST,ALP,和胆红素）与对照组相比，显示了候选药物的肝保护作用，组织学发现证实了这一点。一起来看,槲皮素和姜黄素不仅满足药物样评估标准，并且被证明通过预防肝损伤而具有多靶向性，而且还具有抗癌活性。
