Design of e-pharmacophore models using compound fragments for the trans-sialidase of Trypanosoma cruzi: screening for novel inhibitor scaffolds.

摘要: Chagas’ is a fatal disease that affects millions of people worldwide. The lack safe and effective treatments for highlights the need discovery new drugs to fight disease. Trypanosoma cruzi, parasitic cause disease, synthesizes trans-sialidase (TcTS) enzyme responsible transfer sialic acids from host cell surface glycoconjugates on surface. TcTS has no human analogs vital life cycle T. making an important drug design against We use fragment docking generate various e-pharmacophore hypotheses depicting protein residues ligand binding. Virtual screening ZINC Clean Leads database with more than 4 million compounds using models found 82 potential inhibitors TcTS. Molecular dynamics free energy binding calculations were used rank based their affinity Two compounds—ZINC13359679 ZINC02576132—were be most promising lead candidates inhibition, modes are analyzed in detail.