Interaction between a 3-nitrobenzothiazolo (3,2-a) quinolinium antitumour drug and deoxyribonucleic acid.
The interaction of 3-nitrobenzothiazolo (3,2-a) quinolinium (NBQ) perchlorate with DNA was studied by u.v.-visible and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts, and the fluorescence was quenched. Binding parameters, determined from spectrophotometric measurements by Scatchard analysis according to an excluded-site model, indicated a binding constant of 2.4 X 10(5)M-1 for calf thymus DNA at ionic strength 0.01. The interaction was markedly suppressed by increasing the salt concentration. Binding to the GC-rich DNA of Micrococcus lysodeikticus was weaker than the binding to calf thymus DNA at ionic strength 0.01 NBQ increased the viscosity of sonicated rod-like DNA fragments, producing a calculated increment in length of 2.4 A/bound drug molecule. It removed and reversed the supercoiling of closed circular duplex plasmid pBR322 DNA by virtue of a helix-unwinding angle estimated as approximately 13 degrees/bound ligand molecule. We conclude that the binding of NBQ to DNA occurs by a mechanism of intercalation, which probably accounts for its reported antitumor activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D007364:Intercalating Agents; D009994:Osmolar Concentration; D011806:Quinolinium Compounds / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014783:Viscosity
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011806:Quinolinium Compounds; C038668:3-nitrobenzothiazolo(3,2-a)quinolinium; D004247:DNA