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Bis‐4,9‐diazapyrenium dications: synthesis of the methylenedibenzyl‐analogue, interactions with nucleotides, DNA, RNA. The antitumour activity of all till now prepared analogues
Author(s) -
Piantanida Ivo,
Žinić Mladen,
Marczi Saška,
GlavašObrovac Ljubica
Publication year - 2007
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1165
Subject(s) - chemistry , polynucleotide , dna , nucleotide , rna , dication , stereochemistry , cooperativity , nucleic acid , stacking , dimer , crystallography , biochemistry , molecule , organic chemistry , gene
Abstract 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 bis‐4,9‐diazapyrenium dications prepared till now have shown considerable antiproliferative activity against five human tumour cell lines, which suggested mechanism of action by interacting with cell DNA. Copyright © 2007 John Wiley & Sons, Ltd.