title: Synthesis, structural, and biological evaluation of bis-heteroarylmaleimides and bis-heterofused imides.
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.
authors: Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Nicola
authors: N
authors: Ferri
authors: Tiziano
authors: T
authors: Radice
authors: Manuela
authors: M
authors: Antonino
authors: Egle Maria
authors: EM
authors: Beccalli
authors: Stella
authors: S
authors: Tinelli
authors: Franco
authors: F
authors: Zunino
authors: Alberto
authors: A
authors: Corsini
authors: Graziella
authors: G
authors: Pratesi
authors: Enzio M
authors: EM
authors: Ragg
authors: Maria Luisa
authors: ML
authors: Gelmi
authors: Alessandro
authors: A
authors: Contini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007094:Imides; D008301:Maleimides