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Updated: Aug 16, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis and DNA binding properties of novel benzo[b]isoquino[2,3-h]-naphthyridines
Oliver Koepler1, Stefania Mazzini, Maria Cristina Bellucci
1Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany.
Abstract:
Several benzo[b]isoquino[2,3-h]-naphthyridines have been prepared via formal hetero-Diels Alder reaction of N-aryl imines as a key step. These compounds have different side chains at C-11, and a cis or trans configuration at the C-8a,C-14a ring junction. Binding constants for the interaction with oligonucleotides and polynucleotides were determined by UV absorption and melting experiments. NMR experiments (NOE) revealed that the cis isomers, showing a slightly folded structure, preferentially bind to the minor groove of AT-rich oligomers. In contrast, the trans isomers prefer the CG-rich sequences, leading to cap-complexes with the isoquinoline moiety stacked at the top of the double helix, in agreement with the flatter shape, and with a preference for the 3'-terminals, as found for camptothecins. Models of the complexes were built up by molecular dynamics (MD) calculations, by using the inter-proton distances derived from the NOE values. Cytotoxicity assays against human Ewing sarcoma cell lines RD-ES and CAD-ES1 were performed.
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