1H AND 13C NMR DATA FOR INDOLO[2,3-b]QUINOLINES - AMINOGLYCOSIDE HYBRIDS, A NOVEL POTENT ANTICANCER DRUG FAMILY .

Elżbieta Bednarek Wojciech Bocian Jerzy Sitkowski Agieszka Ulkowska Łukasz S. Kaczmarek 1Katarzyna Badowska-Rosłonek 1Agnieszka Ciesielska 1Lech Kozerski 

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Abstract

The family of indolo[2,3-b]quinolines exhibit significant cytotoxic activity. These tetracyclic, nitrogen heterocycles are synthetically obtained analogs of naturally occuring neocryptolepine, that is used for treatment of infectious diseases. 5,11-Dimethyl-5H-indolo[2,3-b]quinoline (DIMIQ) (I), displaying a structure remarkably close to that of antineoplastic alkaloid ellipticine, was shown to have significant antineoplastic effects on three of experimental tumors. Moreover the derivatives belonging to the 5H- and 6H-indoloquinolinium salts demonstrated significant activity against procaryotic and eucariotic organisms and were cytotoxic in vitro. The active compounds increase DNA denaturation temperature and stimulate the formation of calf thymus topoisomerase II mediated DNA cleavage.

We focused our work on construction an effective anticancer drug by modification of the parent 5H- and 6H-indoloquinoline system. The modification should lead to derivatives combining DNA intercalating and topoisomerase II inhibiting activity with more pronounced affinity to specific sites in polynucleotide chain (DNA sequence reading drug). Such a goal might be achieved in hybrid molecules composed of two parts, which have a defined functions: sequence specificity associated with the groove binding moiety and nuclear targeting promoted by the intercalating indoloquinoline system.

We synthesized aminoglycoside derivatives of indoloquinoline as novel hybrid compounds with potentially pronounced antitumor activity. New molecules consist of intercalating indoloquinoline skeleton and aminocarbohydrate with alkyloxy spacer (II-VII).

The complete assignments of title compounds was carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, GCOSY, GHSQC, GHMBC).

abstract_MKNOL.bmp

 

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Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Agnieszka Ciesielska
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-01-26 18:19
Revised:   2009-06-07 00:44