Design, synthesis, <i>in vitro</i> anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety

<p>The present work describes the design and synthesis of a novel series of 1,3-diaryl-4-sulfonamidoarylpyrazole derivatives <b>1a–q</b> and <b>2a–q</b> and their <i>in vitro</i> biological activities. The target compounds were evaluated for antiproliferative activity against NCI-60 cell line panel. Compounds <b>1c, 1g, 1k–m, 1o, 2g, 2h, 2k–m, 2o</b>, and <b>2q</b> showed the highest mean inhibition percentages at 10 µM single-dose testing and were selected to be tested at 5-dose mode. The ICs<sub>50</sub> of the most potent compounds were determined over the 60 cell lines. Compound <b>2l</b> exhibited the strongest activity against different cell lines with IC<sub>50</sub> 0.33 µM against A498 renal cancer cell line. Compound <b>2l</b> was tested over a panel of 20 kinases to determine its molecular target(s), and its IC<sub>50</sub> values over the most sensitive kinases were defined. <i>In vitro</i> stability and <i>in vivo</i> pharmacokinetic profile of compound <b>2l</b> was also investigated.</p>