Etude comparative de la réactivité de la doxorubicine et de son complexe avec l’acide ascorbique par la DFT conceptuelle.

Abstract

Doxorubicin (DOX), an anthracycline, widely used as antineoplastic agent and shows a broad range of antitumor activity, including acute leukemia, malignant lymphomas, breast cancer. Despite of doxorubicin being potent anticancer therapeutic agent, its clinical usefulness is limited due its cardiotoxicity. A number of mechanisms have been proposed for cardiotoxic effects of DOX, including oxidative stress from free radical-induced myocardial injury, mitochondrial damage, iron-dependent oxidative damage to macromolecules DNA, accumulation of toxic metabolic in the cardiac tissues. Moreover, increased oxidative stress and release of reactive oxygen radicals ROS, as well as antioxidant deficits, have been suggested to play a major role in dox-induced cardiomyopathy. In recent years, there have been growing interests in uses of natural antioxidants as a protective strategy against the cardiovascular. Ascorbic acid is a potent water-soluble antioxidant that scavenges reactive oxygen and nitrogen species and protects cells from oxidative damage. In the present work we aim to study the chemical reactivity of vitamin C in complex with DOX .The complex was studied using DFT at B3LYP level with 6-311++G(d,p) basis set. Molecular properties such as ionization potential (I), electron affinity (A), chemical hardness (ɳ), chemical softness (S), electronegativity (χ), chemical potential (μ) and electrophilicity index (ω) parameters were determined via HOMO and LUMO energies of the complex.