大多数乳腺癌是雌激素受体阳性复发,其稳定速率长达20年,使正常细胞周期失调。Dinaciclib仍在临床试验中,被认为是针对CDK2靶向此类癌症的研究药物。这项研究的主要目的是确定辣木中存在的用于治疗激素受体阳性乳腺癌的CDK-2的潜在抑制剂。为此,计算机技术;分子对接,MM-GBSA和分子动力学模拟用于筛选辣木化合物,并确定其针对CDK-2蛋白靶标的抗癌潜力。在文献报道的36种辣木化合物中,绿原酸(1),槲皮素(2),鞣花酸(3),niazirin(4),山奈酚(5)与靶标显示出良好的亲和力。使用PYMOL软件可视化化合物的相互作用。吸收的轮廓,分布,新陈代谢,使用SWISS和ProToxII网络服务器确定排泄(ADME)和毒性.使用MCF-7癌细胞系体外进行MTT测定以验证辣木叶提取物的抗癌潜力。MTT测定结果显示,在用组分A(石油醚)处理24小时后,Mcf-7细胞的增殖没有显著变化。然而,在200µg/mL剂量的B部分(乙酸乙酯)下观察到显着的抗增殖作用,细胞活力降低至40%。总之,数据表明,所有具有最高负对接得分比参考的化合物可能是潜在的候选细胞周期蛋白依赖性激酶-2(CDK-2)抑制,而鞣花酸,绿原酸和槲皮素是治疗雌激素受体阳性乳腺癌最稳定和最有效的抑制剂,靶向CDK-2。此外,数据表明,需要进一步的研究来确定使用体内模型获得显著抗增殖作用的最佳剂量,以验证我们的计算机模拟分析结果.
Most of the breast cancers are estrogen receptor-positive recurring with a steady rate of up to 20 years dysregulating the normal cell cycle. Dinaciclib is still in clinical trials and considered as a research drug against such cancers targeting CDK2.The major goal of this study was to identify the potential inhibitors of CDK-2 present in Moringa oleifera for treating hormonal receptor positive breast cancers. For this purpose, in silico techniques; molecular docking, MM-GBSA and molecular dynamics simulations were employed to screen Moringa oleifera compounds and their anticancer potential was determined against CDK-2 protein targets. Among 36 compounds of Moringa oleifera reported in literature, chlorogenic acid (1), quercetin (2), ellagic acid (3), niazirin (4), and kaempferol (5) showed good affinity with the target. The interaction of the compounds was visualized using PYMOL software. The profiles of absorption, distribution, metabolism, excretion (ADME) and toxicity were determined using SWISS and ProTox II webservers. The MTT assay was performed in-vitro using MCF-7 cancer cell lines to validate the anticancer potential of Moringa oleifera leaf extract.MTT assay results revealed no significant change in proliferation of Mcf-7 cells following 24 h treatment with fraction A (petroleum ether). However, significant antiproliferative effect was observed at 200 µg/mL dose of fraction B (ethyl acetate) and cell viability was reduced to 40%.In conclusion, the data suggested that all the compounds with highest negative docking score than the reference could be the potential candidates for cyclin dependent kinase-2 (CDK-2) inhibition while ellagic acid, chlorogenic acid and quercetin being the most stable and potent inhibitors to treat estrogen receptor positive breast cancer targeting CDK-2. Moreover, the data suggested that further investigation is required to determine the optimum dose for significant antiproliferative effects using in-vivo models to validate our findings of in-silico analysis.