Rational design of novel compounds to serve as potential NDM-1 inhibitors using molecular docking, molecular dynamics simulation, and physicochemical studies

New Delhi Metallo-β-lactamase (NDM-1) is an enzyme that hydrolyses a wide range of β-lactam antibiotics, including most carbapenems, leading to antimicrobial resistance. The development novel NDM-1 inhibitor for use in combination with carbapenems may help combat drug-resistant pathogens. Twenty compounds were designed based on the structural features active site inhibit bacterial and protect antibiotics from attack. molecules naphthalene, thiazole, sulfone derivatives because they could coordinate zinc ions form hydrophobic contracts enzyme’s site. A molecular docking protocol was used identify potential inhibitor(s) target protein. Furthermore, drug-likeness pharmacokinetic properties predicted. Three more negative ΔGbinding results selected further investigation using dynamic (MD) simulations. T016 had significantly binding free energy than positive control other molecules, stable MD simulations (Root-mean-square deviation < 0.5 Å), passed Lipinski’s rule five, favourable physicochemical properties. findings can be inform synthesis vitro testing molecules.