Binding Modes of Doxorubicin Compared to Estratetrol and Tamoxifen

Abstract

Doxorubicin, a compound isolated from Streptomyces peucetius var Caesius, is commonly
used in the treatment of breast cancer. This drug works by interacting on human nucleic
acids. This work was aimed to study the binding modes of doxorubicin with estrogen receptor
alpha (ERα). Estratetrol and tamoxifen were used as natural ligand and standard drug,
respectively. Molecular docking simulations was performed by AutoDock v.3.05 using minimum
coordinates -34, -6, -15 (x, y, z) and the maximum coordinates -13, 13, 3 (x, y, z).
Tamoxifen formed one hydrogen bond with Glu353 (Ki=3.78 μM); estratetrol binds to Glu-
353, Arg394, Gly521, and His524 (Ki=0.01 μM). Doxorubicin only formed one hydrogen
bond with Ser317 (Ki=N/A). In conclusion, doxorubicin could not interact appropriately
with ERα due to its voluminioues structure which hinder its entrance to binding pocket of
the macromolecule.

Keywords: doxorubicin, estrogen receptor alpha.