Virtual screening of zinc compounds similar to NSAIDS with better pharmacodynamic and pharmacokinetic profiles

BACKGROUND: Pain is a common symptom that managed in both outpatients and inpatients. There are many side effects associated with opioids such as respiratory depression, constipation, hyperalgesia, tolerance. Non- steroidal anti-inflammatory drugs cause gastrointestinal tract (GIT) irritation may be risk factor for developing peptic ulcer disease. This study aimed to generate active analgesic agents from known analgesics, determine the docking scores of these their receptors, pharmacokinetic properties agents, evaluate toxicity profiles. METHODS: PubChem was used download smiles ibuprofen, aspirin celecoxib. Avogadro optimized ligands. The were copied SwissSimilarity query compounds zinc compounds. DrugBank Protein Data Bank cyclooxygenase 1 2. Molecular done using Chimera Autodock Vina. Smiles generated pasted onto Protox II webserver SwissADME pharmacokinetics determination. data presented tabular forms textual descriptions contents tables. RESULTS: Aspirin, ibuprofen celecoxib’s first 20 docked COX-1 COX-2 enzymes. Seven, one, four showed better binding energies than COX-1. analyzed profiles. ZINC01680731 ZINC33823423 predicted have LD50 1240 mg/kg compared aspirin’s 250mg/kg. Ibuprofen ZINC39120409 299mg/kg they hepatoactive. Celecoxib its 1400mg/kg. All had high GIT absorption conformed Lipinski rule five. CONCLUSIONS: 0.994 ZINC00600558 0.988 identified best affinities, toxicities standard compounds.