Design, pharmacokinetic profiling, and assessment of kinetic and thermodynamic stability of novel anti-Salmonella typhi imidazole analogues

Abstract Background Typhoid fever, a disease caused by gram negative bacterial species known as Salmonella typhi , constitutes significant cause of morbidity and mortality, especially in developing nations the world. Antibiotic therapy is major treatment option currently but rising incidences resistance to existing antibiotics has necessitated search for newer ones. The aim this study apply silico techniques design highly potent novel imidazole-based drug candidates that strongly antagonize cell invasion protein (SipA) . Methods In study, set anti- imidazole analogues were subjected molecular docking against an important bacterium SipA using PyRx graphical user interface AutoDock Vina software. best ligand was selected template designing more analogues. Drug-likeness, pharmacokinetic toxicity profiles designed ligands assessed through use Swiss ADME online tool Osiris DataWarrior V5.5.0 chemo-informatics program. Kinetic thermodynamic stabilities ascertained via Density Functional Theory’s Becke-3-parameter Lee–Yang–Parr hybrid functional 6-31 G ** basis set-based quantum chemical calculations. Results bioactive found possess Gibb’s free binding energy (Δ ) values ranging from − 5.4 6.7 kcal/mol active sites protease. Ligand 13 with Δ = used analogues; B-1 B-2 value 7.8 7.6 kcal/mol, respectively, target. When compared ciprofloxacin control 6.8 be potent. Furthermore, drug-likeness ADMET profiling revealed they have excellent oral bioavailability sound profiles. addition, calculations HOMO–LUMO gap 3.58 eV 3.45 eV; global electrophilicity index 4.95 4.79 ligands, indicative their favorable kinetic stabilities. Conclusions It envisaged findings would provide blueprint multidrug resistant