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The mode of action of cyto toxic and anti tumor 1 nitro acridines 1. the 1 nitro acridines do not exert their cyto toxic effects by physicochemical binding with dna

, : The mode of action of cyto toxic and anti tumor 1 nitro acridines 1. the 1 nitro acridines do not exert their cyto toxic effects by physicochemical binding with dna. Chemico Biological Interactions 43(2): 131-150

The mode of action of cytotoxic and antitumor 1-nitroacridines and their isomeric derivatives was studied by comparing their effects in cell-free systems and towards cultured [human cervical cancer] HeLa cells, assuming that the nitroacridines considered exert cytotoxic effects by physicochemical binding with the DNA. All the nitroacridines impaired biosyntheses of DNA, RNA, and protein in cultured HeLa cells and a causal relationship between nitroacridine inhibition of macromolecular biosynthesis and lethal effects of the agents appears likely. In cell-free systems, the nitroacridines bound with 2 independent sites on the DNA, formed complexes with enhanced resistance to DNA strand separation upon melting, and inhibited the DNA polymerase reaction by altering activity of template and/or of enzyme. The 1-nitroacridines were poorly effective in cell-free systems and were the most potent inhibitors toward the growth of HeLa cells among the derivatives studied. The primary events responsible for cytotoxic effects of antitumor 1-nitroacridines and of their isomeric derivatives are probably different. The metabolic activation of 1-nitroacridines to more reactive intermediates which will attach to and alter the structure and/or function of sensitive cells is suggested.

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