Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy
ACS Omega ( IF 3.7 ) Pub Date : 2020-10-14 , DOI: 10.1021/acsomega.0c03975
Mohd Yousuf 1 , Parvez Khan 2 , Anas Shamsi 2 , Mohd Shahbaaz 3, 4 , Gulam Mustafa Hasan 5 , Qazi Mohd Rizwanul Haque 1 , Alan Christoffels 3 , Asimul Islam 2 , Md Imtaiyaz Hassan 2
ACS Omega ( IF 3.7 ) Pub Date : 2020-10-14 , DOI: 10.1021/acsomega.0c03975
Mohd Yousuf 1 , Parvez Khan 2 , Anas Shamsi 2 , Mohd Shahbaaz 3, 4 , Gulam Mustafa Hasan 5 , Qazi Mohd Rizwanul Haque 1 , Alan Christoffels 3 , Asimul Islam 2 , Md Imtaiyaz Hassan 2
Affiliation
|
Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 107 M–1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6–quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors.
中文翻译：
通过槲皮素抑制 CDK6 活性是一种有吸引力的癌症治疗策略
细胞周期蛋白依赖性激酶 6 (CDK6) 是一个潜在的药物靶点，在不同类型癌症的进展中发挥着重要作用。我们对不同的天然化合物进行了计算机和体外筛选，发现槲皮素对 CDK6 具有高结合亲和力，并抑制其活性，IC 50 = 5.89 μM。 CDK6-槲皮素复合物的分子对接和 200 ns 全原子模拟提供了对该复合物的结合机制和稳定性的深入了解。通过荧光和等温滴定量热法研究确定的结合参数揭示了槲皮素与 CDK6 的结合常数在 10 7 M –1范围内。与 CDK6-槲皮素复合物形成相关的热力学参数表明静电相互作用驱动的过程。乳腺癌 (MCF-7) 和肺癌 (A549) 细胞中基于细胞的蛋白质表达研究表明，槲皮素治疗可降低 CDK6 的表达。槲皮素还降低选定癌细胞的活力和集落形成潜力。此外，槲皮素通过减少活性氧的产生和 CDK6 的表达来诱导细胞凋亡。计算机模拟和体外研究都强调了槲皮素对于开发 CDK6 抑制剂抗癌先导化合物的重要性。
更新日期：2020-10-28
中文翻译：
通过槲皮素抑制 CDK6 活性是一种有吸引力的癌症治疗策略
细胞周期蛋白依赖性激酶 6 (CDK6) 是一个潜在的药物靶点，在不同类型癌症的进展中发挥着重要作用。我们对不同的天然化合物进行了计算机和体外筛选，发现槲皮素对 CDK6 具有高结合亲和力，并抑制其活性，IC 50 = 5.89 μM。 CDK6-槲皮素复合物的分子对接和 200 ns 全原子模拟提供了对该复合物的结合机制和稳定性的深入了解。通过荧光和等温滴定量热法研究确定的结合参数揭示了槲皮素与 CDK6 的结合常数在 10 7 M –1范围内。与 CDK6-槲皮素复合物形成相关的热力学参数表明静电相互作用驱动的过程。乳腺癌 (MCF-7) 和肺癌 (A549) 细胞中基于细胞的蛋白质表达研究表明，槲皮素治疗可降低 CDK6 的表达。槲皮素还降低选定癌细胞的活力和集落形成潜力。此外，槲皮素通过减少活性氧的产生和 CDK6 的表达来诱导细胞凋亡。计算机模拟和体外研究都强调了槲皮素对于开发 CDK6 抑制剂抗癌先导化合物的重要性。
京公网安备 11010802027423号