Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University (Girls), Cairo 11754, Egypt.
Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, Egypt.
Molecules. 2018 Nov 24;23(12):3074. doi: 10.3390/molecules23123074.
A series of novel 1,3,4-triarylpyrazoles containing different heterocycles has been prepared, characterized and screened for their in vitro antiproliferative activity against HePG-2, MCF-7, PC-3, A-549 and HCT-116 cancer cell lines. The biological results revealed that compound showed the highest anticancer activity so it was subjected to a kinase assay study where it reduced the activity of several protein kinases including AKT1, AKT2, BRAF V600E, EGFR, p38α and PDGFRβ at 100 μM using the radiometric or ADP-Glo assay method. Molecular docking simulation supported the initial kinase assay and suggested a common mode of interaction at the ATP-binding sites of these kinases, which demonstrates that compound is a potential agent for cancer therapy deserving further research.
已经合成了一系列含有不同杂环的新型 1,3,4-三芳基吡唑，并对其进行了表征和体外抗增殖活性筛选，以评估它们对 HePG-2、MCF-7、PC-3、A-549 和 HCT-116 癌细胞系的抑制作用。生物实验结果表明，化合物 表现出最高的抗癌活性，因此对其进行了激酶测定研究，结果显示，在 100μM 浓度下，该化合物通过放射性或 ADP-Glo 测定法，能抑制 AKT1、AKT2、BRAF V600E、EGFR、p38α 和 PDGFRβ 等多种蛋白激酶的活性。分子对接模拟实验结果支持了初步的激酶测定结果，并提示了化合物与这些激酶的 ATP 结合位点的一种共同作用模式，这表明化合物 是一种有潜力的癌症治疗药物，值得进一步研究。
