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DNA and RNA interactions of benzimidazole amidines with antitrypanosomal activity

A series of novel benzimidazole amidines derivatives are synthesized at the Department of Organic Chemistry, Faculty of Chemical Engineering and Technology. They differ only in one substituent (–F vs –H vs –OCH3) attached on phenyl ring (Figure 1.). These three compounds were selected for the binding study with DNA and RNA based upon their antitrypanosomal activity. Binding of studied compounds to DNA and RNA polynucleotides (ctDNA, poly(dAdT)2, poly(dGdC)2 and poly A – poly U) was monitored with the fluorescence spectroscopy. CD titrations and DTm experiments were used for a determination of the binding modes (intercalation, groove binding, external binding).Interestingly, despite the fact that even benzimidazole amidines derivatives differ only in one substituent, they caused opposite changes in fluorescence upon interaction with studied polynucleotides. While addition of derivatives 1 and 2 caused a decrease of fluorescence in the presence of DNA/RNA, the addition of any polynucleotide resulted exclusively in strong emission increase of derivative 3 which can probably be ascribed to donor properties of methoxy group. All three compounds exhibited positive induced CD spectra (ICD) with ctDNA, poly(dAdT)2 and poly A – poly U. Usually, a positive ICD band, with an intensity similar or stronger than CD band of DNA/RNA, strongly supports the minor groove binding to DNA or the major groove binding to ds-RNA.1 Thus, it can be concluded that studied compounds bind to minor groove of ctDNA and AT-DNA and to major groove of ds-RNA.

DNA ; benzimidazole ; amidines ; minor groove ; fluorescence ; spectroscopy ; CD titrations

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