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Synthesis, Antitumor Activity and Interaction with DNA of Imidazolinyl Substituted Benzo[b]Thieno[2, 3-c]Naphthiridinones

As a part of our continuinig search for potential anticancer agents related to heterocyclic quinolones, we have synthesized novel imidazolinyl substituted acyclic amido-benzo[b]thiophenes and their cyclic derivatives benzo[b]thieno[2, 3-c]naphthiridinones. Substituted heterocyclic quinolones have attracted considerable attention from medicinal and synthetic organic chemists because of the wide range of biological activities displayed by this class of compounds. Earlier prepared class of substituted benzo[b]thieno[2, 3-c]quinolones and thieno[3', 2':4, 5]thieno[2, 3-c]quinolones showed strong and selective antitumor activity as well as strong intercalative binding with ds-DNA/RNA. Here we present the synthesis of above mentioned compounds starting from benzo[b]thiophene-2-carbonyl chloride which gave in the reaction with cyano-amino-pyridines corresponding acyclic amides. Their cyclic derivatives were prepared by reaction of photochemical dehydrohalogenation. Imidazolinyl substituted derivatives were prepared by Pinner reaction. All compounds were tested on their antitumor activity. Spectroscopic studies of the interaction of cyclic 3-4 derivatives with ct-DNA supported strong binding to DNA which is in good agreement with their antitumor activity. References [1] Jarak I. ; Kralj, M. ; Šuman, L ; Pavlović, G ; Dogan J ; Piantanida, I. ; Žinić, M ; Pavelić, K. ; Karminski-Zamola, G. ; J. Med. Chem. 48 (2005) 2346-2360. [2] Jarak, I. ; Kralj, M ; Piantanida, I ; Šuman, L. ; Žinić, M ; Pavelić, K ; Karminski-Zamola, G. ; Bioorg. & Med. Chem. 14 (2006) 2859-2868. [3] Natarajan, S. R. et al., Bioorg. & Med. Chem. Lett. 16 (2006) 5468-5471.

benzo[b]thieno[2; 3-c]naphthiridinones; amidines; antitumor activity; interaction with DNA

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