Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains

An experimental and theoretical study was performed on the anti-staphylococ cal activity of 18 natural and synthetic flavonoids against methicillin-res istant Staphylococcus aureus strains. The analysed flavonoids belong to thr ee well-differentiated structural patterns: chalcones, flavanones and flavo nes. The quantitative analysis of the anti-staphylococcal activity of the c ompounds was carried out by determining their percent inhibition degree. Th e hierarchical cluster analysis method was used to analyse the anti-MRSA ac tivity of the compounds. With this methodology, the flavonoids were classif ied into four groups according to their antistaphylococcal activity thigh, sufficient, intermediate and low). The carbonylic region is of importance b ecause it is part of the bioactive region inducing anti-MRSA activity in th e flavonoid molecules. The introduction of OH groups in positions 2' of cha lcones and 5 of flavanones (or flavones) increases flavonoid activity, whil e the OCH3 groups produce the reverse effect. Using the experimental anti-M RSA activity data of flavonoids and six quantum chemical parameters calcula ted by means of the AM1 semiempirical molecular orbital method, a very good quantitative structure-activity relationship was obtained (confidence rang e: 95%; significance level for tests: 0.05; correlation coefficient = 0.984 2). The selected parameters explain 96.86% of the percent inhibition degree . The obtained relation is consistent with the conclusions formulated in th is 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)-ch alcone and 2',4(OH)(2)-chalcone might constitute promising therapeutic agen ts against infections with methicillin-resistant S. aureus strains. (C) 200 0 Academic Press.