Synthesis, structural, and biological evaluation of bis- heteroarylmaleimides and bis-heterofused imides

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

Research output: Contribution to journalArticlepeer-review

Abstract

Bis-2,3-heteroarylmaleimides and polyheterocondensed imides joined through nitrogen atoms of the N,N′-bis(ethyl)-1,3-propanediamine linker were prepared from substituted maleic anhydrides and symmetrical diamines in good to satisfactory yields and short reaction times using microwave heating. The novel molecules were shown to inhibit proliferation of human tumor cells (NCI-H460 lung carcinoma) and rat aortic smooth muscle cells (SMCs) with variable potencies. Compound 11a, the most potent one of the series, showed IC 50 values comparable to those observed for the leading molecule elinafide in both cell lines, but with a higher selectivity toward human tumor cells. Compound 11a affected G1/S phase transition of the cell cycle, showed in vitro DNA intercalating activity and in vivo antitumor activity. A thorough structural analysis of the 11a-DNA complex was also made by mean of NMR and computational techniques.

Original languageEnglish
Pages (from-to)5291-5299
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number18
DOIs
Publication statusPublished - Sep 15 2011

Keywords

  • Biological activity
  • DNA intercalator
  • Microwave chemistry
  • Molecular dynamics
  • NMR spectroscopy

ASJC Scopus subject areas

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

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