title: Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains.
abstract: An experimental and theoretical study was performed on the anti-staphylococcal activity of 18 natural and synthetic flavonoids against methicillin-resistant Staphylococcus aureus strains. The analysed flavonoids belong to three well-differentiated structural patterns: chalcones, flavanones and flavones. The quantitative analysis of the anti-staphylococcal activity of the compounds was carried out by determining their percent inhibition degree. The hierarchical cluster analysis method was used to analyse the anti-MRSA activity of the compounds. With this methodology, the flavonoids were classified into four groups according to their anti-staphylococcal activity (high, sufficient, intermediate and low). The carbonylic region is of importance because it is part of the bioactive region inducing anti-MRSA activity in the flavonoid molecules. The introduction of OH groups in positions 2' of chalcones and 5 of flavanones (or flavones) increases flavonoid activity, while the OCH(3)groups produce the reverse effect. Using the experimental anti-MRSA activity data of flavonoids and six quantum chemical parameters calculated by means of the AM1 semiempirical molecular orbital method, a very good quantitative structure-activity relationship was obtained (confidence range: 95%; significance level for tests: 0.05; correlation coefficient=0.9842). The selected parameters explain 96.86% of the percent inhibition degree. The obtained relation is consistent with the conclusions formulated in this paper and serves as a theoretical support for some of them. Finally, it is concluded that the flavonoids chalcone, 2'(OH)-chalcone, 2',4'(OH)(2)-chalcone and 2',4(OH)(2)-chalcone might constitute promising therapeutic agents against infections with methicillin-resistant S. aureus strains.
authors.affiliation: Facultad de Química, Areas de Bacteriología y Química-Física, San Luis, 5700, Argentina.
authors.forename: L E
authors.initials: LE
authors.lastname: Alcaráz
authors.forename: S E
authors.initials: SE
authors.lastname: Blanco
authors.forename: O N
authors.initials: ON
authors.lastname: Puig
authors.forename: F
authors.initials: F
authors.lastname: Tomás
authors.forename: F H
authors.initials: FH
authors.lastname: Ferretti
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D002599:Chalcone / Q000819:agonists / Q000627:therapeutic use; D016000:Cluster Analysis; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D005419:Flavonoids; D002599:Chalcone