Structure–Bioactivity-Relationships and Crystallographic Analysis of Secondary Interactions in Pregnane-Based Steroids

Abstract

A total of eighty-seven molecules of pregnane-based steroids (1–87) 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 descriptors for active and inactive fragments. The probable activities are characterized by Pa and Pi values which depict that most of the molecules have high value of teratogen activity. The biological activity spectra for substances have been correlated on SAR base (structure–activity relationships data and knowledge base) which provides the different Pa (probability of activity) and Pi (probability of inactivity). The Lipinski’s rule predicts that most of pregnane derivatives have stronger preponderance for “cancer-like-drug” molecules and some of their related analogous have been entered in the American National Cancer Institute database. The CCDC survey sets out to collate existing data on pregnane derivatives and its interpretations with special emphasis on intra- and intermolecular hydrogen bonds. X–H···A intra/intermolecular hydrogen bonds in the identified molecules have been described with the standard distance and angle cut-off criteria. D–θ and d–θ scatter plots for X–H···A intra- and intermolecular interactions are presented for better understanding of packing interactions existing among these derivatives. Comparison of contacts from H(C) to O and H(O) to O, vis-a-vis their crystal structure reveals that contacts from H(O) to O predominate over H(C) to O. The hydrogen interactions between crystallographic independent molecules represent a rich hunting ground for understanding packing in the solids. Bifurcated hydrogen bonds have been identified in some molecules and most of these bonds are based on C–H···O pattern in which ‘O’ atom acts as a prototype acceptor. 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 show high value of drug-likeness; whereas molecule-5(87.5%), 25 (87.4%), 34 (88.6%), 45 (89.9%), 58 (81.4%), 67 (87.2%) and 83 (89.9%) exhibit low value of drug-likeness, instead of observed range of 91.2–99.4%. Biochemical processes are transformations that occur in living organisms involve a great variety of steroids, proteins, lipids, carbohydrates, etc. and these complex substances make up some portion of the total weight of biochemical systems in which main constituent is water. Steroidal molecules are held in their defined 3-D structures by hydrogen bonds. The solvent–solute/solute–solvent interactions [O5(Methanol)–H(Methanol)···O3; O17–(HO17)···O5(Methanol)] for a pregnane derivative are plotted in Figure. These interactions greatly influence the behaviour of compounds. In biological–activity the ubiquitous presence of solvent affects many macroscopic results, such as excretion. The possibility of modeling such interactions can reduce experiments and permit better understanding of compound activity.