Diflerence spectrophotometry shows that double-stranded DNA produces mnarked changes in the absorption spectrum of chloroquine; only minor changes occur with single-stranded DNA. A DNA-chloroquine complex was demonstrated to sediment in the analytical ultracentrifuge. Chloroquine strongly elevated the thermal dissociation temperature, T(m), of DNA. It is concluded that the drug forms a complex with DNA by ionic interaction and stabilizes the helix.
The drug chloroquine is bactericidal for Bacillus megaterium; it inhibits DNA and RNA biosynthesis and produces rapid degradation of ribosomes and dissimilation of ribosomal RNA. Inhibition of protein synthesis is also observed, evidently as a secondary effect. Inhibition of DNA replication is proposed as a general mechanism of the antimicrobial action of chloroquine.
A complex of calf-thymus DNA with berberine sediments in the analytical ultracentrifuge. The DNA produced systematic changes in the absorption spectrum of berberine which suggest that single alkaloid molecules bind to DNA. Flow dichroism of purines and pyrimidines and of berberine in the complex with DNA had the same signs and magnitudes. Berberine shifted the thermal strand separation profile of DNA to higher temperatures. Therefore, the alkaloid forms a complex with DNA, probably by intercalation.
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