Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides

A series of 2,3-heteroarylmaleimides 9 and polyheterocondensed imides 12 were prepared in good yields and short reaction time using a very efficient procedure consisting in the condensation of the corresponding anhydrides and N,N-diethylethylenediamine and microwave heating. The antiproliferative activity of the novel molecules was tested against human tumor cells (NCI-H460 lung carcinoma) and rat aortic smooth muscle cells (SMCs). The IC50 values for the novel molecules ranged from 0.08 to 13.9 μM in SMCs, and from 0.84 to 9 μM in the tumor cell line. The activity profile for compounds 9 and 12 is comparable to that obtained for amonafide in NCI-H460, except for fused imides 12b,i which proved to be about 10-fold more potent. Whereas, in rat SMCs, only the compound 12b was shown to be 10-fold more potent than amonafide. Instead 12c is equipotent to amonafide. These results suggest that the extended π-system and the kind of heteroatom are essential in the binding with the molecular target.

A series of 2,3-heteroarylmaleimides and polyheterocondensed imides were prepared and their antiproliferative activity was tested against human tumor cells (NCI-H460 lung carcinoma) and rat SMCs.Figure optionsDownload as PowerPoint slide