M. Consuelo Jaramillo, Cristina Mora, Luis E. Velez and Jairo Quijano Pages 434 - 439 ( 6 )
Staphyloccoccus aureus, Escherichia coli, Pseudomona aeruginosa Klebsiella pneumoniae, Acinetobacter baumannii, Enetrobacter cloacae and more bacterias have shown resistance to antibiotics in Colombia, therefore, resistance to antibiotics is a problem that is on increase in Colombia. The resistance mechanism to penicillin antibiotics in these bacterias is the expression of β-Lactamase enzyme. In order to use the penicillin antibiotics which are still effective against them, we had evaluated 10 chalcones as inhibitors of this enzyme. The most active chalcone showed Km = 406.7 μM higher than clavulanic acid that showed Km = 211.9 μM at 37oC during 10 h, and using amoxycillin as substrate. The chalcones were better competitive inhibitors because of they allowed the hydrolysis of smaller quantity of amoxycillin than the clavulanic acid, the most active chalcone showed Kcat/KM = 1.398 (minM)-1 and the clavulanic acid showed Kcat/KM = 2.674 (minM)-1. The molecular modelling of the Enzyme-chalcones complexes showed that the chalcones with electron-donating groups on ortho, meta position of A ring favour the interaction with the residues Threonine-319, Lysine- 67, Serine-64 and Tyrosine-150 of the active site of the enzyme, because of the number and strong of Hydrogen bonds of the chalcones in the active site of the enzyme increase, and therefore the affinity of the chalcones increases too. The electron- donating groups in the chalcones contribute to their inductive effect improving the interaction with the active site of the enzyme because of rising of electrostatic attraction between them.
β-Lactamase, chalcones, molecular modelling, inhibitory activity, amoxycillin, clavulanic acid
Laboratorio de Sustancias Bioactivas, Sede de Investigacion Universitaria, Universidad de Antioquia. Carr. 53 =-30. Medellin, Colombia. Departamento de Farmacologia y Toxicología, Facultad de Medicina, Universidad de Antioquia. A.A. 1226, Spain.