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.

Synthesis, Structural and Biological Evaluation of Bis-Heteroarylmaleimides and Bis-Heterofused Imides / N. Ferri, T. Radice, M. Antonino, E. Beccalli, S. Tinelli, F. Zunino, A. Corsini, G. Pratesi, E.M. Ragg, M.L. Gelmi, A. Contini. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 19:18(2011 Sep 15), pp. 5291-5299. [10.1016/j.bmc.2011.08.016]

Synthesis, Structural and Biological Evaluation of Bis-Heteroarylmaleimides and Bis-Heterofused Imides

N. Ferri
Primo
;
T. Radice
Secondo
;
E. Beccalli;A. Corsini;E.M. Ragg;M.L. Gelmi
Penultimo
;
A. Contini
Ultimo
2011

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.
DNA intercalator; Microwave chemistry; NMR spectroscopy; Molecular dynamics; Biological activity
Settore CHIM/06 - Chimica Organica
Settore BIO/14 - Farmacologia
15-set-2011
16-ago-2011
Article (author)
File in questo prodotto:
File Dimensione Formato  
Biorg_2011.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.14 MB
Formato Adobe PDF
1.14 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/164643
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 24
social impact