TY - JOUR
T1 - Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides
AU - Ferri, Nicola
AU - Beccalli, Egle Maria
AU - Contini, Alessandro
AU - Corsini, Alberto
AU - Antonino, Manuela
AU - Radice, Tiziano
AU - Pratesi, Graziella
AU - Tinelli, Stella
AU - Zunino, Franco
AU - Gelmi, Maria Luisa
PY - 2008/2/15
Y1 - 2008/2/15
N2 - 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.
AB - 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.
KW - 2,3-Heteroarylmaleimides
KW - Antiproliferative activity
KW - NCI-H460
KW - Polyheterocondensed imides
KW - Smooth muscular cells
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UR - http://www.scopus.com/inward/citedby.url?scp=38949146706&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.11.024
DO - 10.1016/j.bmc.2007.11.024
M3 - Article
C2 - 18061459
AN - SCOPUS:38949146706
VL - 16
SP - 1691
EP - 1701
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 4
ER -