Advances in Chemotherapy

**155**

**Chapter 9**

**Abstract**

**1. Introduction**

of Anthracyclines

an effective, selective, and safe anti-cancer drugs.

*and Sonika Charak*

Molecular-Level Understanding of

the Anticancer Action Mechanism

*Manish Shandilya, Shrutika Sharma, Prabhu Prasad Das* 

Anthracyclines drugs are used as a treatment regime to combat cancer owing to their great chemotherapeutic potential. They are characterized by the presence of a wide range of derivatives, the most famous are doxorubicin and daunorubicin. The proposed action mechanism of anthracyclines and their derivatives to exert cytotoxic effect involves the intercalation of the drug molecule into nucleic acid and inhibition of the activity of topoisomerases. These events consequences in halting DNA replication and transcription mechanisms of the cell. Understanding of the structural and conformational changes associated with nucleic acid after binding with drugs provides significant knowledge for the development of more effective drugs. A comprehensive elucidation of the molecular mechanism(s) of action of anthracyclines drugs plays a significant role in the rational drug designing to obtain

**Keywords:** anthracycline, anti-cancer activity, DNA, molecular mechanism

Anthracyclines were primarily recognized as antibiotics due to their antibacterial properties in 1939 [1]. However, the chemical characterization of the anthracyclines which includes a rigid planar aromatic ring that remains bound to an amino-sugar by a glycosidic bond (**Figures 1** and **2**). Quinone and hydroquinone groups of these molecules on adjacent rings allow gain and loss of electrons in the conversion of quinone to the semiquinone radical [2, 3]. This semiquinone free radical converts back to quinine under aerobic conditions resulting in the formation of superoxide anion and hydrogen peroxide. The excessive formation of these free radical consequences in lipid peroxidation within cell membranes, DNA damage and finally cell death. This makes them the potent non-selective anti-cancer drugs i.e., they are used in the treatment of a wide range of cancer like small cell lung cancer, breast cancer, lymphoblastic and myeloblastic leukemia, etc. [1, 4–6]. There is a high probability that a cancer patient will be administered with anthracycline at some stage of their chemotherapy session. Daunomycin and doxorubicin were the earliest anthracyclines isolated from *Streptomyces peucetius* and were effective against a wide range of human cancers. Owing to significant antitumor potential, the World Health Organization (WHO) has included daunomycin and doxorubicin
