Le. Alcaraz et al., Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains, J THEOR BIO, 205(2), 2000, pp. 231-240
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.