DNA: Reaction with Chloroquine

Abstract

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.

Studies on the complex of distamycin a with calf thymus DNA

“…5A). Single-stranded DNA, prepared as described previously [7] , also induced Cotton effects in the ORD spectrum of DMC but these were of lesser molecular amplitudes than those shown in fig. 5A.…”

Stage independent chloroquine resistance and chloroquine toxicity revealed via spinning disk confocal microscopy

“…It is striking that a reduction in schizont nuclei is now also defined to be a result of CQ toxicity, and that this occurs regardless whether CQ is administered at R, T or S. As CQ disturbs Hz formation primarily by acting on heme and heme-related compounds, reactive oxygen species created as a result of this chemistry might be damaging DNA or DNA replication machinery, and therefore indirectly decrease the amount of the DNA formed during S. This explanation also requires early Hb catabolism in R. Alternatively the explanation could be more complicated, and involve yet undescribed interactions between CQ (or CQ -heme conjugates) and cyclins or other molecules that regulate the poorly understood nuclear division during S, or perhaps even direct interaction between DNA and CQ or CQ -heme adducts [2][3][4][5][6][7][8][9].…”

“…However, none of these models easily explained much lower inhibitory concentrations of CQ for P. falciparum vs. mammalian cells ( ~ 1000 -10,000 fold lower). Thus the nucleic acid hypotheses have been largely discounted, particularly after the discovery that the P. falciparum genome was highly AT rich whereas CQ preferentially interacts with GC-rich DNA [9].…”

Efficient polyethylenimine-mediated gene delivery proceeds via a caveolar pathway in HeLa cells

“…Because of its aromatic ring structure, chloroquine is able to intercalate DNA, thereby causing a conformational change that is capable of inhibiting enzymatic DNA degradation. 35,36 The addition of 5 mM chloroquine prevents total DNA digestion, as evidenced by the faint pGL3…”