title: [Inhibitory activity of dihydroxy-phenyl-propenone on betalactamase of Enterobacter cloacae : preliminary study for drug development to overcome bacterial resistance. ].
abstract: BACKGROUND
  Enterobacter cloacae is a pathogenic microorganism with the ability to produce betalactamase enzymes, which makes them resistant to betalactamic antibiotics. Additionally, the limited activity of enzymatic inhibitors has been identified, and, therefore, the design of new drugs and the promotion of their rational use are the only possibilities to overcome this problem.
  
  
  OBJECTIVE
  The aim of this research was to evaluate the effect of dihydroxy-phenyl-propenone on a clinical isolate of E. cloacae , as well as its activity on a betalactamase isolated from this resistant microorganism in order to contribute to the search for new betalactamase inhibitors.
  
  
  METHODS
  Dihydroxy-phenyl-propenone chalcone was synthesized and evaluated on a clinical isolate of E. cloacae to determine the minimum inhibitory concentration by broth microdilution; once the betalactamase enzyme was purified by affinity chromatography, a spectrophotometric analysis was done to evaluate its kinetic activity.
  
  
  RESULTS
  The minimum inhibitory concentration value of dihydroxy-phenyl-propenone on E. cloacae was 35 µg/ml; the recovery percentage of the betalactamase from the microorganism was 31.75% and the kinetic parameters were V max =1.7 x 10 -3 µM/min and K M = 2330 µM, which show an important inhibitory activity.
  
  
  CONCLUSIONS
  Dihydroxy-phenyl-propenone has shown inhibitory activity on betalactamase enzymes and the ability to protect the chemical integrity of betalactamic antibiotics; this synergistic effect turns it into a promising compound in the search for new alternatives to overcome bacterial resistance.
authors: Grupo de Investigación en Sustancias Bioactivas, Sede de Investigación Universitaria, Universidad de Antioquia.
authors: Cristina Lucía
authors: CL
authors: Mora
authors: Grupo de Investigación en Sustancias Bioactivas, Sede de Investigación Universitaria, Universidad de Antioquia.
authors: Julián
authors: J
authors: Castaño
authors: Grupo de Investigación en Sustancias Bioactivas, Sede de Investigación Universitaria, Universidad de Antioquia.
authors: María Consuelo
authors: MC
authors: Jaramillo
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002846:Chromatography, Affinity; D015169:Colony Count, Microbial; D003124:Colorimetry; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000201:enzymology; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D010405:Penicillinase / Q000302:isolation & purification / Q000378:metabolism*; D000078142:Tazobactam; D018440:beta-Lactam Resistance / Q000187:drug effects*; D065093:beta-Lactamase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000596546:1-(4-methylphenyl)-3-(2,3-dihydroxyphenyl)-2-propenone; D001426:Bacterial Proteins; D047188:Chalcones; D065093:beta-Lactamase Inhibitors; D000667:Ampicillin; D010397:Penicillanic Acid; D010405:Penicillinase; D000078142:Tazobactam