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

Abstract

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.

• Authors: Nicola Ferri, Egle Maria Beccalli, Alessandro Contini, Alberto Corsini, Manuela Antonino, Tiziano Radice, Graziella Pratesi, Stella Tinelli, Franco Zunino, Maria Luisa Gelmi
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 4 Pg. 1691-701 (Feb 15 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18061459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Imides
• Maleimides

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Aorta
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cells, Cultured
• Humans
• Imides (chemical synthesis, pharmacology)
• Inhibitory Concentration 50
• Maleimides (chemical synthesis, pharmacology)
• Muscle, Smooth, Vascular (cytology, drug effects)
• Rats
• Structure-Activity Relationship