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

Autori
Piantanida, Ivo ; Žinić, Mladen ; Marczi, Saška ; Glavaš-Obrovac, Ljubica

Izvornik
Journal of Physical Organic Chemistry (0894-3230) 20 (2007), 4; 285-295

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

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

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

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