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Circular dichroism (CD) spectra of complexes of 4-benzylaminopyrimido[4′,5′ :4,5]selenolo(2,3-b)quinoline (BAPSQ) with octanucleotide I (d(TGACGTCA)), which is the cAMPresponsive element (CRE) in gene promoters, and its inverse d(ACTGCAGT) (octanucleotide II) have been measured over a range of drug/DNA ratios. It was demonstrated that the anticancer polyaromatic drug BAPSQ intercalates into DNA basepairs with its long direction perpendicular to both the DNA helix axis and the base pair long axis and induces larger conformational changes in CpG containing octanucleotide I CRE than in its reverse sequence, octanucleotide II. It was concluded that CD is a powerful and sensitive technique to discriminate between drug-binding modes of DNA and to define the geometry of the chromophore inserted into base pairs. [ABSTRACT FROM AUTHOR]

The interaction between double-stranded (ds) DNA and the 4-butylamino pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline (BPSQ) has been studied with spectral luminescence methods. Binding constant values determined by absorption and fluorescence titration indicated a binding constant of 4.24 × 104 and 5.9 × 104 M−1, respectively. The interaction was markedly suppressed by increasing the salt concentration. BPSQ exhibited a strong specificity for the guanine–cytosine (GC) sequence in total DNA at an ionic strength of 0.01 (5.54 × 106 M−1). BPSQ increased the viscosity of sonicated rod-like DNA fragments, producing a calculated increment in length of 2.4 Å per bound drug molecule. A circular dichroism experiment showed that BPSQ might interact with DNA according to two possible binding modes depending on its structure and concentration. The first mode concerned intercalation of BPSQ with its long axis perpendicular to the long axis of the DNA helix. The same drug was able to bind to external sites, second mode, once the intercalation sites were saturated at high concentration. The results from cytotoxicity assays indicate that BPSQ was found to be toxic to all cell lines tested with IC50 values ranging from 2.8 to ≥ 20 µM. It was concluded that the binding of BPSQ to DNA occurs by a mechanism of intercalation, which probably accounts for its reported antitumor activity. [ABSTRACT FROM AUTHOR]