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首页> 外文期刊>Archiv der Pharmazie >New Coumarin Derivatives as Anti-Breast and Anti-Cervical Cancer Agents Targeting VEGFR-2 and p38 MAPK
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New Coumarin Derivatives as Anti-Breast and Anti-Cervical Cancer Agents Targeting VEGFR-2 and p38 MAPK

机译：新的香豆素衍生物作为抗乳腺和抗宫颈癌剂靶向VEGFR-2和P38 MAPK

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Breast and cervical cancers are the most common gender-specific cancers affecting women worldwide. In this investigation, we highlighted the synthesis, VEGFR-2 and p38 MAPK inhibitory activity of new series of fluorinated coumarin-based derivatives featuring a variety of bioactive chemical moieties attached or fused to the coumarin nucleus at the 3 and/or 4 position. The bioactive inhibitors were further assessed for their anti-proliferative effect against human MCF-7 breast cancer and HeLa cervical cancer cell lines, respectively. Most of the tested compounds showed potent preferential inhibition effects against human VEGFR-2 and remarkable anticancer activities in the human breast cancer cell line MCF-7. Compounds 29, 24, and 2 displayed the highest inhibitory activity against VEGFR-2 (94% inhibition) and they were the most potent anticancer agents toward MCF-7 cancer cells with IC50 values of 7.90, 8.28, and 8.30g/mL, respectively. Compound 13 inhibited p38 MAPK phosphorylation with a significant reduction in % cell viability against HeLa cancer cells at 10 and 30 mu M. Docking experiments carried out on VEGFR-2 and p38 MAPK crystallographic structures revealed that the active compounds bind to the active sites through H-bonds, arene-cation, and hydrophobic - interactions. QSAR analysis demonstrated considerable correlation coefficient (R-2=0.76969) and root mean square error (RMSE=0.10446) values. Also, the residual values between the experimental pIC(50) and predicted pIC(50) are very close, indicating the reliability of the established QSAR model.
机译：乳腺癌和宫颈癌是影响全世界妇女的最常见的性别特异性癌症。在这项研究中，我们强调了新系列氟化香豆素的衍生物的合成，VEGFR-2和P38 Mapk抑制活性，其各种生物活性化学部分在3和/或4个位置融合到香豆素核。进一步评估生物活性抑制剂，分别对人MCF-7乳腺癌和HeLa宫颈癌细胞分别进行抗增殖作用。大多数测试化合物对人类乳腺癌细胞系MCF-7中的人VEGFR-2和显着的抗癌活性显示有效的优先抑制作用。化合物29,24和2展示了VEGFR-2（94％抑制）的最高抑制活性，并且它们分别是MCF-7癌细胞的最有效的抗癌剂，IC 50值分别为7.90,8.28和8.30g / ml 。化合物13抑制P38Mapk磷酸化，在10和30μmM的Hela癌细胞上显着降低了％细胞活力。在VEGFR-2和P38 MAPK晶体结构上进行的对接实验表明，活性化合物通过H结合活性位点 - 粘合剂，芳烃和疏水性 - 相互作用。 QSAR分析表现出相当大的相关系数（R-2 = 0.76969）和均均方误差（RMSE = 0.10446）值。而且，实验照片（50）和预测的PIC（50）之间的残余值非常接近，表明所建立的QSAR模型的可靠性。

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