**4.1. Doxorubicin's chemical structure**

The chemical structure of DOX is {(7*S*, 9*S*)-7-[(2*R*, 4*S*, 5*S*, 6*S*)-4-amino-5-hydroxy-6-methyloxan-2-yl] oxy-6, 9, 11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8, 10-dihydro-7*H*-tetracene-5, 12-dione (**Figure 2**). Due to structural specifications with a tetracycline moiety containing a quinone and a conjugated amino sugar residue, DOX can undergo metabolic modification by enzymes dominantly in the liver and kidneys during the elimination process. Some oxidoreductase enzymes, especially nicotinamide adenine dinucleotide phosphate (NADPH) dependent cytochrome P450 reductases at the endoplasmic reticulum (ER), nicotinamide adenine dinucleotide (NADH) dehydrogenase (complex I) at the electron transport chain (ETC), and cytosolic xanthine oxidase, have been suggested to play an important role in DOX elimination. The oxidoreductase enzyme can convert DOX to its semiquinone form by using molecular oxygen [13].

DOX's structure includes a glycoside group with anthraquinone moiety. The structure is responsible for its antineoplastic activity and also its toxicity [14]. DOX contains a tetracyclic ring with two quinone-hydroquinones and daunosamine. Though the tetracyclic sugar is nonsoluble in water, daunosamine sugar is soluble in water. DOX has been produced in a derivative form, e.g., daunorubicin. The difference between DOX and daunorubicin is only in the hydroxyl groups. Even though there is a slight difference between the drugs, their

**Figure 2.** The chemical structure of doxorubicin antibiotics. From Imstepf et al. [27].

activities very are different to each other. How DOX intercalates DNA is related to the drug's chemical structure, including its chromophore's hydroxyl and daunosamine sugar's amino groups [22] (**Figure 2**).
