Computational Quantum Chemical Study, Drug-Likeness and In Silico Cytotoxicity Evaluation of Some Steroidal Anti-Inflammatory Drugs

This paper contains a theoretical study of ten Anti-inflammatory steroids (AIS) on the understanding of the relationship between the structure and activity of the drug, the pharmacokinetic parameters responsible for bioavailability and bioactivity and finally the toxicity evaluation. DFT calculations with B3LYP/6-31G (d, p) level have been used to analyze the electronic and geometric characteristics deduced for the stable structure of the compounds. Moreover, using the Frontier Molecular orbital (FMO) energies, MEP surface visualizations and the density-based descriptors such as chemical potential (µ), electronegativity (χ), hardness (η) and softness (σ), the chemical stability were determined. Furthermore, in silico, studies showed that Lipinski rules are applied, which means that these (AIS) are expected to have a high probability of good oral bioavailability. On the other side, the bioinformatic Osiris/Molinspiration analyses of the relative cytotoxicity of these derivatives are reported in comparison to Cortisol. In fact, it has been showed that almost of these compounds are non-toxics except for Mometasone that presents a great risk of tumorigenicity during reproduction with a slightly mutagenic structure due to the two chloride atoms. from all results obtained, we can conclude that fluticasone has the best physico-chemical properties which explains its high efficiency. Keywords: Anti-inflammatory steroids, DFT, Lipinski rules, Tumorigenicity