Naturalne i syntetyczne pochodne 5,8-chinolinodionu wykazujące aktywność biologiczną

The compounds produced by a living organisms are most commonly used as medicinal agents and starting materials to the preparation of new semi-synthetic derivatives. It is estimated that over 23% of currently used medicinal products are natural substances. Natural compounds and their semisynthetic derivatives are most often used in the treatment of cancer and the treatment of infectious diseases. One of the groups of compounds obtained from Gram-positive bacterium are 5,8-quinolinedione antibiotics, like: streptonigrin, lavendamycin and streptonigron. The all compounds exhibit high anticancer, antimicrobial and antiviral activity. Unfortunately due to high toxicity this alkaloids did not find place in the therapy. The mechanism of action depends on interaction of compounds with the nicotinamide quinone oxidoreductase 1 (NQO1). The 5,8-quinolinedione can be reduced by the NAD(P)H as a cofactor to form the semiquinone or hydroquinone intermediates. These compounds can react with oxygen yielding a regenerated 5,8-quinolinedione fragment and creating the hydroxyl radicals, which are ultimately responsible for the DNA strands cleavage. The structure–activity relationship study has shown that the most important part of the molecule is the 5,8-quinolinedione moiety. Furthermore, it was found, that the introduction of amine, hydroxyl or thiol substituents at position 6 or 7 of the 5,8-quinolinedione moiety results in an enhanced biological activity. A lot of synthetic derivatives of 5,8-quinolinediones which containing amine, alkoxyl and thiol groups at the C-6 or/and C-7 positions have been obtained during the last few years. Commonly this compounds are obtained in the reaction of 6,7-dichloro-5,8-quinolinedione with nucleophilic factor. Depending on the reaction conditions, mono- or di-substituted derivatives are obtained. Most of synthesized compounds exhibit high biological activity, like: anticancer, antibacterial, antiviral, anti-inflammatory.