Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors

Quantitative structure–activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum–chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic–androgenic receptor binding site. The calculated values predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene compound presents the highest anabolic–androgenic ratio (AAR) and the 7α-methyl-17β-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of “real” or “virtual” anabolic–androgenic steroids.

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► Quantum and physicochemical molecular descriptors allow new Quantitative structure–activity relationship (QSAR) models to predict their anabolic and androgenic activities of steroids.
► These new models for androgenic activity also explain the steroid–receptor interaction, which is mostly due to the biological activity expressed by electronic descriptors.
► Calculated values for the anabolic–androgenic ratio (AAR) predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene steroid present the higher AAR and the 7α-methyl-17β-acetoxy-estr-4-en-3-one the lowest AAR in agreement with the experimental data.