Alcaráz L E, Blanco S E, Puig O N, Tomás F, Ferretti F H
Facultad de Química, Areas de Bacteriología y Química-Física, San Luis, 5700, Argentina.
J Theor Biol. 2000 Jul 21;205(2):231-40. doi: 10.1006/jtbi.2000.2062.
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.
对18种天然和合成黄酮类化合物针对耐甲氧西林金黄色葡萄球菌菌株的抗葡萄球菌活性进行了实验和理论研究。所分析的黄酮类化合物属于三种差异明显的结构模式：查耳酮、黄烷酮和黄酮。通过测定化合物的抑制百分度对其抗葡萄球菌活性进行定量分析。采用层次聚类分析法分析化合物的抗耐甲氧西林金黄色葡萄球菌（MRSA）活性。用这种方法，根据黄酮类化合物的抗葡萄球菌活性（高、足够、中等和低）将其分为四组。羰基区域很重要，因为它是黄酮类分子中诱导抗MRSA活性的生物活性区域的一部分。在查耳酮的2'位和黄烷酮（或黄酮）的5位引入羟基会增加黄酮类活性，而甲氧基则产生相反的效果。利用黄酮类化合物的实验抗MRSA活性数据和通过AM1半经验分子轨道方法计算的六个量子化学参数，得到了很好的定量构效关系（置信区间：95%；检验显著性水平：0.05；相关系数 = 0.9842）。所选参数解释了抑制百分度的96.86%。所得关系与本文得出的结论一致，并为其中一些结论提供了理论支持。最后得出结论，查耳酮、2' - 羟基查耳酮、2',4' - 二羟基查耳酮和2',4 - 二羟基查耳酮可能构成针对耐甲氧西林金黄色葡萄球菌菌株感染的有前景的治疗剂。
