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.
A series of new 20 corticosteroids were subjected to molecular property prediction. The Molecular, Physicochemical, and Biological properties were determined using Molinspiration Cheminformatics software. These compounds were further subjected to Toxicity Predictions using the Osiris Software. The calculated drug-related properties of the designed molecules were similar to those found in most marketed drugs. Amongst the proposed molecules, fourteen promising candidates can be considered as promising structures for the synthesis of new and more effective anti-asthmatic drugs. Result indicates that the derivatives are orally active molecules. In-silico ADME and toxicity prediction was accomplished with the help of Swiss-ADMET tool provides the latest and most inclusive for diverse chemicals associated with known Absorption, Distribution, Metabolism, Excretion and Toxicity profiles. furthermore, BBB (Blood brain barrier) penetration, HIA (Human intestinal absorption), Caco-2 cell permeability and Ames test were calculated using ADMET web-based query tools incorporating a molecular build in interface enable the database to be queried by Smiles and structural similarity search. According to molecular docking results, derivatives No 4, 10 and 11 showed better docking Scores values compared to other derivatives and also dexamethasone and hydrocortisone.
Keywords: Corticosteroids, Drug-likeness, Lipophilicity, Anti-asthmatic, ADME.
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