天然来源黄酮类化合物与抗凋亡BCL-2和BCL-XL蛋白用于卵巢癌治疗的分子对接研究
Molecular Docking Study of Naturally Derived Flavonoids with Antiapoptotic BCL-2 and BCL-XL Proteins toward Ovarian Cancer Treatment.
作者信息
Abd Ghani Mohd Faiz, Othman Rozana, Nordin Noraziah
机构信息
Department of Basic Medical Sciences, Faculty Medicine & Health Sciences, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia.
School of Pharmacy, KPJ Healthcare University College, Nilai, Malaysia.
出版信息
J Pharm Bioallied Sci. 2020 Nov;12(Suppl 2):S676-S680. doi: 10.4103/jpbs.JPBS_272_19. Epub 2020 Nov 5.
The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin-Bcl-xl protein complex (-8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from -8.0 to -8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin-Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers.
天然衍生的黄酮类化合物具有抗癌作用,这是众所周知的。由于据报道现有的铂类药物会产生耐药性且生存率低,黄酮类化合物可能是治疗卵巢癌的一种替代策略。抑制抗凋亡蛋白,即B细胞淋巴瘤(Bcl - 2)和Bcl - 2超大蛋白(Bcl - xl),是刺激癌细胞凋亡过程的关键靶点。本研究旨在确定五种天然衍生的黄酮类化合物(鹰嘴豆芽素A、杨梅素、芹菜素、高良姜素和漆黄素)与潜在的抗凋亡靶蛋白(Bcl - 2和Bcl - xl)之间的结合相互作用。使用AutoDock Vina程序进行分子对接研究。预测了黄酮类化合物与靶蛋白之间的结合亲和力和氢键的存在。我们的研究结果表明,所有黄酮类化合物与Bcl - xl的结合亲和力均优于与Bcl - 2蛋白的结合亲和力。漆黄素 - Bcl - xl蛋白复合物的结合亲和力最高(-8.8千卡/摩尔)。同时,与Bcl - xl蛋白对接的其他黄酮类化合物的结合亲和力在-8.0至-8.6千卡/摩尔之间。在对接的漆黄素 - Bcl - xl复合物中总共检测到四个氢键、四个疏水接触和一个静电相互作用,这解释了其与Bcl - xl的高结合亲和力。目前的结果表明,所有黄酮类化合物都可能作为Bcl - xl蛋白抑制剂,从而导致卵巢癌的凋亡过程。
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