Mechanism of Selective Inhibition of Yohimbine and Its Derivatives in Adrenoceptor α2 Subtypes

Some natural alkaloids from medicinal plants, such as yohimbine and its derivatives, have been reported with adrenoceptor (AR) alpha 2 subtypes inhibiting activity. In trying to address the possible mechanism of the action, a set of homology models of AR alpha 2 was built based on MOE. After that, docking and molecular dynamics methods were used to investigate the bindingmodes of yohimbine and its 2 derivatives in the active pocket of adrenoceptor alpha 2 subtype A, B, and C. The key interactions between the 3 ligands and the 3 receptors were mapped. Binding mode analysis presents a strong identity in the key residues in each subtype. Only a few differences play the key role in modulating selectivity of yohimbine and its derivatives. These results can guide the design of new selective AR alpha 2 inhibitors.