**2.2 How anthracyclines damage DNA?**

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**Figure 5.**

**Figure 4.**

*sequences.*

*nucleotide sequences.*

towards their therapeutic effects.

on mitochondrial toxicity. The effect of doxorubicin binding on the morphology of the single stranded DNA was further quantitatively analyzed using Atomic Force Microscopy (AFM). AFM studies strengthen the probable mechanism of intercalative binding mode as consequences of doxorubicin interaction with DNA [15].

*Intercalation of epirubicin and idarubicin between GC basepairs. Crystal structure of epirubicin getting intercalated between AT and GC basepairs. Crystal structure of idarubicin getting intercalated between GC bases. Structures are taken from protein data bank. Red dots represent crystallized water molecules. Figure clearly depicts intercalation of epirubicin and idarubicin in GC bases of DNA and preferential binding with* 

*Intercalation of daunorubicin between GC basepairs. Crystal structure of daunorubicin getting intercalated between GC bases. Structures are taken from protein data bank. Light green color depicts AT baseparing and dark green color shows GC bases. Red dots represent crystallized water molecules. Figure clearly depicts intercalation of doxorubicin in GC bases of DNA and preferential binding with nucleotide* 

Other studies found that B-DNA is preferred over Z-DNA by the daunorubicin for binding. Allosteric conversion of the Z form into B form has also been observed in some cases. Ionic concentration in which usually Z form of DNA is present changes to B form on the binding of daunorubicin to poly dGdC or resist to change from B form to Z form [16]. There are several pieces of evidence suggesting drug binding to DNA results in the inhibition of specific DNA function contributing

Anthracyclines are known to damage DNA by several mechanisms which include topoisomerase-II poisoning, free radical formation, and DNA-anthracycline adduct formation. The semiquinone radical of anthracycline can intercalate between DNA base pair resulting in DNA damage by forming reactive oxygen species (ROS).
