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

Nicola Ferri, Egle Maria Beccalli, Alessandro Contini, Alberto Corsini, Manuela Antonino, Tiziano Radice, Graziella Pratesi, Stella Tinelli, Franco Zunino, Maria Luisa Gelmi

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)1691-1701
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number4
DOIs
Publication statusPublished - Feb 15 2008

Keywords

  • 2,3-Heteroarylmaleimides
  • Antiproliferative activity
  • NCI-H460
  • Polyheterocondensed imides
  • Smooth muscular cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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