Design synthesis in vitro anticancer evaluation kinase inhibitory effects and pharmacokinetic profile of new 134-triarylpyrazole derivatives possessing terminal sulfonamide moiety

摘要

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 ICs50 of the most potent compounds were determined over the 60 cell lines. Compound >2l exhibited the strongest activity against different cell lines with IC50 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 IC50 values over the most sensitive kinases were defined. In vitro stability and in vivo pharmacokinetic profile of compound >2l was also investigated.