a Medicinal & Pharmaceutical Chemistry Department , Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC) , Dokki , Giza , Egypt.
b Department of Medicinal Chemistry , College of Pharmacy, University of Sharjah , Sharjah , United Arab Emirates.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):97-109. doi: 10.1080/14756366.2018.1530225.
The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives 1a-q and 2a-q and their in vitro biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds 1c, 1g, 1k-m, 1o, 2g, 2h, 2k-m, 2o, and 2q showed the highest mean inhibition percentages at 10 µM single-dose testing and were selected to be tested at 5-dose mode. The ICs of the most potent compounds were determined over the 60 cell lines. Compound 2l exhibited the strongest activity against different cell lines with IC 0.33 µM against A498 renal cancer cell line. Compound 2l was tested over a panel of 20 kinases to determine its molecular target(s), and its IC values over the most sensitive kinases were defined. In vitro stability and in vivo pharmacokinetic profile of compound 2l was also investigated.
本工作描述了一系列新型 1,3-二芳基-4-磺酰胺基芳基吡唑衍生物 1a-q 和 2a-q 的设计与合成及其体外生物活性。对目标化合物进行了抗 NCI-60 细胞系的体外增殖活性评价。在 10 μM 单剂量测试中，化合物 1c、1g、1k-m、1o、2g、2h、2k-m、2o 和 2q 表现出最高的平均抑制率，因此选择它们进行 5 剂量模式测试。对最有效的化合物进行了 60 个细胞系的 IC 值测定。化合物 2l 对不同细胞系表现出最强的活性，对 A498 肾癌细胞系的 IC 0.33 μM。化合物 2l 在 20 种激酶的组合中进行了测试，以确定其分子靶标，并确定其对最敏感激酶的 IC 值。还研究了化合物 2l 的体外稳定性和体内药代动力学特征。
