engleski

Guanidiniocarbonyl-pyrrole-aryl derivatives : structure tuning for spectrophotometric recognition of specific DNA and RNA sequences and antiproliferative activity

We present here a systematic study of different guanidiniocarbonyl-pyrrole-aryl derivatives designed to interact with DNA or RNA both by intercalation of an aromatic moiety into the base stack of the nucleotide as well as groove binding of a guanidinio-carbonyl pyrrole cation. We varied 1.) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2.) the length and flexibility of the linker connecting the two binding groups, as well as 3.) the total number of positive charges present at different pH values. The compounds and their interaction with DNA and RNA were studied by UV/Vis-, fluorescence and CD spectroscopy. Also the antiproliferative activity against human tumour cell lines was determined. Our studies show that efficient interaction with e.g. DNA requires a significantly large aromatic ring (pyrene) connected via a flexible linker to the pyrrole moiety. However, a positive charge as in 12 is also needed. Compound 12 allows for a base pair selective recognition of ds-DNA at physiological pH. The antiproliferative activity correlates with the binding affinity of these compounds towards DNA suggesting that the biological effect is most likely due to DNA binding.

DNA/RNA binding ; intercalation ; molecular recognition ; antiproliferation

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