engleski

Bis-4, 9-diazapyrenium dications: synthesis of the methylenedibenzyl- analogue, interactions with nucleotides, DNA, RNA. The antitumor activity of all till now prepared analogues.

Novel bis-4, 9-diazapyrenium dication has shown reversible pH dependent formation of 4, 9-diazapyrenium pseudobase in water characteristic for most 4, 9-diazapyrenium derivatives. The compound has formed non-covalent complexes with nucleotides in water, whose stability is controlled dominantly by aromatic stacking interactions. No cooperativity between two 4, 9-diazapyrenium subunits was observed in binding of nucleotides. Novel bis-4, 9-diazapyrenium dication formed mono-intercalative complexes with studied double stranded DNA and RNA. Additional interactions of non-intercalated part were found to depend significantly on the polynucleotide secondary structure, yielding strong DNA over RNA preference. Appearance of ICD band of 3 was found to be specific for DNA polynucleotides and together with observed destabilisation of double stranded RNA is attributed to the aggregation of compound in one of the RNA grooves. All till now prepared bis-4, 9-diazapyrenium dications have shown considerable antiproliferative activity against five human tumour cell lines, what suggested mechanism of action by interacting with cell DNA.

bis-4; 9-diazapyrenium cations; DNA; RNA; intercalation; antiproliferative activity; antitumour activity

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