Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones

• Condensation of aroylpropionic acids with (p-(methylsulfonyl)phenylhydrazine) gave sixteen new pyridazinones.
• Eleven pyridazinones were selected for antiproliferative studies by NCI.
• Compound 2f was most active against 36 human tumor cell lines with GI50 <1 μM.
• Compound 2f was more active than the standard drug 5-fluorouracil in 29 different cell lines.
• Pyridazinones 2k and 2n showed comparable anti-inflammatory activity to the standard drug etoricoxib.

Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones (2a–p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d, 2e–j and 2m–p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 μM on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 μM. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h.

Compounds 2f and 2g are potent antiproliferative agents whereas compounds 2k and 2n have comparable anti-inflammatory activity to the drug etoricoxib.Figure optionsDownload as PowerPoint slide