Nitrocarbazoles: studies on their electron accepting properties, enzymatic reactivity and cytotoxicity

摘要

Carbazole derivatives, possessing NO_2 groups, are widely used in different fields of industry. 1,3,6,8-Tetranitrocarbazole (TNC) found its application in military practice for the illuminating andfirring material formulations. In this work, six nitro- carbazole compounds (NCs) were synthesized by different nitration methods. The product structures were confirmed by spectral methods. The electronic characteristics of NCs and their electron-accepting potency were assessed by quantum mechanical methods. The enzymatic reactivity of NCs towards single- and two-electron/hydride-transferring flavoenzymes was examined. It has been found that the enzymatic reduction of TNC, as one of the most reactive NCs, was accompanied by formation of its main reductive azoxy-type product [MW=646.41] as confirmed by LC-MS method. The cytotoxic effects of certain selected NCs were examined against mammalian cell lines applying primary mice splenocytes. The concentrations of NCs for 50 % cell survival (CL_(50)) were defined to be equal to 75 microM (TNC), 88 microM (1,3,6-TriNC), 50 microM (3,6-DNC) and 150 microM (3-MNC). The cytotoxic effect of NCs was found to be in the range of nitroaromatic model compound 1,3-dinitrobenzene (CL_(50)=100 microM) and markedly lower than that of TNT(CL_(50)=10 microM) or tetryl (CL_(50) = 6 microM).