Yildiz I, Ertan T, Bolelli K, Temiz-Arpaci O, Yalcin I, Aki E
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara University, Tandogan, Ankara, Turkey.
SAR QSAR Environ Res. 2008 Jan-Mar;19(1-2):101-13. doi: 10.1080/10629360701844159.
Considering the worth of developing new antibacterial agents against drug-resistant Stapylococcus aureus, the present study explores the structure-activity relationships analysis of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and phenylacetamide derivatives using classical QSAR and 3D-common-feature pharmacophore hypothese approaches. QSAR analysis revealed that the compounds possessing a methylene group between the phenyl and the carboxyamido moiety played a role for decreasing the activity. On the other side, substituent effects on position R1 was found important for the activity and holding a substituent possessing a minimum width property on this position like as alkyl groups enhanced the activity. Moreover, substituting position R3 with a group enhancing the electron-donor capability of the phenolic ring system increased the potency. 3D-common-feature pharmacophore approach considered that the conformational properties of the compounds were important for the activity against drug-resistant S. aureus and compounds possessing a benzamide moiety rather than phenylacetamide structure increased the activity. Furthermore, holding NO2 and OH groups on the phenyl ring attached to the benzamide moiety was important for improving the potency against drug-resistant S. aureus.
鉴于开发新型抗耐药金黄色葡萄球菌抗菌剂的价值，本研究采用经典定量构效关系（QSAR）和三维共同特征药效团假说方法，对N-(2-羟基-4(或5)-硝基/氨基苯基)苯甲酰胺和苯乙酰胺衍生物进行构效关系分析。QSAR分析表明，在苯基和羧酰胺部分之间具有亚甲基的化合物对活性降低起作用。另一方面，发现R1位的取代基效应对于活性很重要，并且在该位置上具有如烷基等具有最小宽度性质的取代基会增强活性。此外，用增强酚环系统给电子能力的基团取代R3位会提高效力。三维共同特征药效团方法认为，化合物的构象性质对于抗耐药金黄色葡萄球菌的活性很重要，并且具有苯甲酰胺部分而非苯乙酰胺结构的化合物会增加活性。此外，在连接到苯甲酰胺部分的苯环上带有NO2和OH基团对于提高抗耐药金黄色葡萄球菌的效力很重要。
