title: The phenanthridine biguanides efficiently differentiate between dGdC, dAdT and rArU sequences by two independent, sensitive spectroscopic methods.
abstract: At submicromolar concentrations two novel phenanthridine biguanides exhibit distinctly different spectroscopic signals for dGdC and dAdT sequences, respectively, by opposite fluorimetric changes (quenching for dGdC and increase for dAdT) and especially the bis-biguanide derivative gives an opposite ICD response (negative ICD for dGC and strong positive for dAdT). This specific signalling was explained by the ability of compounds to switch the binding mode from intercalation into dGdC to minor groove binding into dAdT sequences. Both compounds bind to rArU by intercalation, yielding different fluorimetric and CD response in comparison to any of aforementioned ds-DNA. Moreover, both compounds revealed significantly higher affinity toward ds-polynucleotides in comparison to previously studied alkylamine- and urea-analogues. Furthermore, DNA/RNA binding properties of novel compounds could be controlled by pH, due to the protonation of heterocyclic nitrogen. Low in vitro cytotoxicity of both compounds against human cell lines makes them interesting spectrophotometric probes.
authors: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, PO Box 180, HR-10002 Zagreb, Croatia.
authors: Marijana
authors: M
authors: Radić Stojković
authors: Snežana
authors: S
authors: Miljanić
authors: Katarina
authors: K
authors: Mišković
authors: Ljubica
authors: L
authors: Glavaš-Obrovac
authors: Ivo
authors: I
authors: Piantanida
mesh_terms: D000818:Animals; D001645:Biguanides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010617:Phenanthridines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001645:Biguanides; D007364:Intercalating Agents; D010617:Phenanthridines; D012313:RNA; D004247:DNA