Minor Structural Differences of Monomethine Cyanine Derivatives Yield Strong Variation in Their Interactions with DNA, RNA As Well As on Their in Vitro Antiproliferative Activity

Comparison of binding properties of a series of monomethine cyanine derivatives to ds-DNA and ds-RNA revealed significant impact of the properties of substituent attached to the longer axis of aromatic core. Namely, it seems that only compounds 7, 8 characterised by length of longer axis not exceeding the length of longer axis of basepairs could intercalate into ds-DNA and ds-RNA, while the increased substituent length and additional possibility of hydrogen bonds formation directed binding of 1-6 into ds-DNA minor groove. Consequent ds-RNA over ds-DNA selectivity of 7 and 8 is the most appealing and rather rare property among small molecules. The interactions of 1-8 with ss-RNA were strongly dependent on both, structure of compound and base composition of RNA. The cytotoxicity screening of compounds 1-8 by MTT test revealed considerable antiproliferative activity against solid tumours and especially toward haematological malignancies (IC(50)=0.001-6.6 microM), whereby normal human aortic endothelial cells (HAEC) were significantly less affected (IC(50)=1-200 microM). The cells of chronic myeloid leukaemia in blast crisis (K562) were especially sensitive to all tested compounds (IC(50)=0.001-0.6 microM), while normal lymphocytes were more resistant (IC(50)=0.01-1 microM). Results of uptake and intracellular distribution of compounds 1 and 2 in the living cells showed that they do not bind primarily to nuclear DNA but their fluorescence is scattered through the whole cells. A detailed mechanism of antitumor activity of tested molecules remains to be investigated.