Synthesis and evaluation of biological activity from two steroid-diazacyclododecin derivatives on left ventricular pressure

There are several studies which indicate that some cardiovascular diseases are relationship with biological activity of estrogens through of its receptors activation. The objective of this work was synthesizing two new steroid-diazacyclododecin derivatives (compounds 11 or 12) to evaluate their effect on left ventricular pressure in Langendorff model using as control to 17 β -estradiol. In addition, a theoretical study was carried out to evaluate the interaction of compound 11 or 12 with the estrogen receptor (3os8 protein) using a docking model. The experimental results showed that only the compound 12 decreased left ventricular pressure in a similar form to 17 β -estradiol. In addition, other experimental data showed that effect exerted by 17β-estradiol was inhibited in presence of 12. Finally, theoretical results indicated that interaction of 12 with 3os8 protein involved some aminoacid residues such as Pro₂₂₄, Leu₃₁₉, Leu₃₂₀, Leu₃₂₇, Asp₃₂₁, Ala₃₂₂, Glu₃₂₃, Pro₃₂₄, Pro₃₂₅, Ile₃₂₆ and Leu₃₂₇. All these data suggest that compound 12 may act as a selective agonist of estrogen receptor which translated as changes on left ventricular pressure.