„IN SILICO“ PREDICTION OF PHARMACOKINETIC PROPERTIES AND DRUGLIKENESS OF NOVEL THIOUREA DERIVATIVES OF NAPROXEN

Masking the carboxyl group of naproxen with other functional groups may be a promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described as an important pharmacophore in a variety of pharmacologically active compounds, including anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research group has previously designed twenty novel thiourea derivatives of naproxen, containing amino acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine – compounds 1,2,3,4 and 5, respectively), their methyl (6–10) and ethyl esters (11–15), as well as aromatic amines (16–20). Pharmacokinetic properties and druglikeness of these compounds were predicted using SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties include potential for gastrointestinal absorption, blood-brain barrier permeability, skin permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential. Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as well as on the basis of bioavailability score. All tested compounds had high-predicted gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7, 9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with aromatic amines (16–20) showed inhibitory potential against all tested CYP isoforms. Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin permeability. Finally, derivatives 1–12, except 5 and 10, have druglike structures, since they obey to all imposed rules.

Efficient and Facile Synthesis of Benzimidazole Induced Schiff Bases and their Potent Antibacterial Activity and Computational Study

Synthesized benzimidazole induced Schiff base analogues were characterized by mass, 13C NMR, 1H NMR and UV-visible spectroscopy. To get more information about binding mechanism, molecular docking studies were carried out and the obtained results concluded that the compounds could effectively bind with receptor. in vitro Antibacterial screening was carried out against four strains (S. aureus, B. subtilis, P. aeruginosa and E. coli) and exhibited good antibacterial activity. The gastrointestinal absorption (HIA) and brain penetration (BBB) was evaluated by The BOILED-Egg model, which showed that two compounds anticipated being effectively effluated by the P-glycoprotein from central nervous system after penetration and can accounts for brain access and passive gastrointestinal absorption. Computational screening showed 0.55 bioavailability score for all synthesized compounds.