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.
Ferri
Nicola
N
Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy.
Beccalli
Egle Maria
EM
Contini
Alessandro
A
Corsini
Alberto
A
Antonino
Manuela
M
Radice
Tiziano
T
Pratesi
Graziella
G
Tinelli
Stella
S
Zunino
Franco
F
Gelmi
Maria Luisa
ML
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