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 microM in SMCs, and from 0.84 to 9 microM 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 pi-system and the kind of heteroatom are essential in the binding with the molecular target.
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy.
Nicola
N
Ferri
Egle Maria
EM
Beccalli
Alessandro
A
Contini
Alberto
A
Corsini
Manuela
M
Antonino
Tiziano
T
Radice
Graziella
G
Pratesi
Stella
S
Tinelli
Franco
F
Zunino
Maria Luisa
ML
Gelmi
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001011:Aorta; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008301:Maleimides / Q000138:chemical synthesis / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007094:Imides; D008301:Maleimides