Biological-Activity Predictions and Hydrogen-Bonding Analysis of Estrane Derivatives of Steroids

Abstract

A total of twenty molecules of estrane derivatives of steroids have been included to predict their pharmacological effects, specific mechanisms of action, known toxicities, drug likeness, etc., by using the statistics of multilevel neighbourhoods of atoms (MNA) descriptors for active and inactive fragments. The biological activity spectra for substances have been correlated on Structure–activity relationships base (SAR data and knowledge base) which provides the different P_a (possibility of activity) and P_i (possibility of inactivity). Most of the probable activities are characterized by P_a and P_i values which depict that all the molecules have high value of teratogen activity. The Lipinski’s thumb rule predicts that all the estrane derivatives have stronger preponderance for “cancer-like-drug” molecules and some of their related analogous have been entered in the ANCI (American National Cancer Institute) database. D-θ and d-θ scatter plots for X–H···A intermolecular interactions are presented for better understanding of packing interactions which exist in estrane derivatives. Comparison of contacts from H(C) to O and H(O) to O, vis-à-vis their crystal structure reveals that contacts from H(O) to O predominate over H(C) to O. Few bifurcated hydrogen bonds based on O–H···O pattern have been observed while trifurcated O–H···O hydrogen bond has been observed only in one molecule (i.e. XVII). Solvent–solute/solute–solvent interactions have also been investigated to understand more complicated processes that occur for biomolecules in aqueous solutions. Most of the molecules have high probability of drug-likeness whereas molecule XIX (71.0%) and XX (86.4%) has low value of drug-likeness instead of observed range of 90.4–99.2%.

Graphical Abstract