Selección de nuevos antibacterianos por tipología molecular

  1. Simón García, Victoria Eugenia
Supervised by:
  1. Facundo Pérez Giménez Director
  2. Francisco José García March Director

Defence university: Universitat de València

Fecha de defensa: 19 May 2005

  1. José Luis Moreno Frigols Chair
  2. María Teresa Salabert Salvador Secretary
  3. Stella Moreno Grau Committee member
  4. Enrique Hernández Giménez Committee member
  5. Marina Herráez Domínguez Committee member

Type: Thesis

Teseo: 103268 DIALNET lock_openTDX editor


The molecular topology has been used to obtain the numeric characterization of series of molecules with antibacterial activity of the fluorquinolones group, using a set of topologic index describers of the molecular structure. After the obtaining of the relationships Q.S.A.R. and the connectivity functions, the discriminante lineal analysis is carried out that allows to obtain a function able to discern, of among to group of chemical compounds, those that possess the wanted activity. Those compounds that show theoretical activity are subjected to pharmacological rehearsals. In a first phase, tests of antimicrobial susceptibility are carried out, to show their activity and the predictive capacity of the proposed method, after that which, those structures that show activity, are subjected to rehearsals of sharp toxicity in experimentation animals. As a result, it was found that the discriminant function obtained, by means of the computer package BMDP, is able to discern, with a high success degree, the structures that possess antibacterial activity of those that don't present it, being reached percentages of success of 99.11% and 97.16% for the active and inactive set respectively of the group of training and of 100% and 97% for the same set of molecules of the group test. By means the discriminant function obtained a molecular selection is carried out, being obtained a total of fifteen products with theoretical antibacteriana activity displaying values of ?P>5, which are later on subjected to microbiológicos rehearsals showing activity seven of them. The determination of the intraperitoneal DL50 in mouse for the seven products that presented antimicrobial activity allows us to demonstrate and to check the scarce toxicity of two of them, the products N-[4-(2-Benzoxazolil)fenil]maleimide and 1,1'-(Metilene-di-4,1-fenilen) bismaleimide, which have therapeutic margins of considerable width, because the first one presents values of DL50 between ten and twenty times superior to those of IMC obtained respectively in front of Enterococcus faecalis and Staphylococcus aureus; while the second it have values of DL50 between three and six times superiors to its values of IMC in front of Enterococcus faecalis and Staphylococcus aureus respectively. The obtained results confirm completely the validity of the topologic method used, in the prediction and discrimination of the antimicrobial activity, as well as in the search and selection of new structures with theoretical antimicrobiana activity.