Synthesis and biological evaluation of novel coumarin–pyrazoline hybrids endowed with phenylsulfonyl moiety as antitumor agents

Two groups of coumarin–pyrazoline hybrids were synthesized. The target compounds were obtained by cyclization of the coumarin chalcones with various substituted hydrazines to produce the corresponding pyrazolines through 1,4-addition on α,β-unsaturated carbonyl system. Selected compounds were investigated for their anticancer activity toward 60 cancer cell lines according to US NCI protocol where breast cancer MCF7 and colon cancer HCT-116 were the most susceptible to the influence of compounds 7d, 8c and 9c. Encouraged by this, all final compounds were screened against colorectal cell line HCT-116. The tested compounds exhibited high potency with IC50 ranging from 0.01 μM to 2.8 μM. Moreover, compound 9c which possessed the highest cytotoxicity proved to have weak enzyme inhibitory activity against PI3K (p110α/p85α).

Two groups of coumarin-pyrazoline hybrids bearing either (un)-substituted phenylsulfonyl or terminal sulfamoyl moiety were synthesized as potential antitumor agents utilizing the patent compounds IX as lead.Figure optionsDownload as PowerPoint slideHighlights
► Two groups of coumarin-pyrazoline hybrids were synthesized.
► Selected compounds were tested toward 60 cell lines according to US NCI protocol.
► All compounds were screened against HCT-116.
► The most active compounds were screened for PI3K (P110α/p85α) inhibition.