Lak Parnia, Amini Mohsen, Safavi Maliheh, Shafiee Abbas, Shahverdi Ahmad Reza
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Medical Sciences/University of Tehran, Tehran, Iran.
Arzneimittelforschung. 2008;58(9):464-8. doi: 10.1055/s-0031-1296540.
In this study, 3-alkyl and 3-aryl esters of hexahydroquinoline derivatives were screened for their ability to decrease bacterial resistance to ciprofloxacin (CAS 85721-33-1), which is extensively used to treat bacterial infections. A group of 3-alkyl and 3-aryl esters of hexahydroquinoline derivatives in which 2-aryl thiazole is substituted at 4-position were synthesized. The enhancement of the antibacterial activity of ciprofloxacin by these new synthetic compounds was evaluated against a resistant clinical strain of Staphylococcus aureus. The agar disk diffusion method was used to determine the antibacterial activity of different synthetic compounds in the absence and presence of ciprofloxacin. These results indicate that the antibacterial effect of ciprofloxacin is enhanced by two 3-alkyl esters of hexahydroquinoline derivatives (7b-3 and 7b-4).The enhancing effect of 7b-4 on the antibacterial activity of ciprofloxacin was greater than that of compound 7b-3. In comparison to the other synthetic compounds, 7b-4 showed a 5.61-fold increase of the inhibition zone on the ciprofloxacin supplemented plates. The result demonstrated that compounds 7b (3 and 4) could serve as valuable probes to study the structure-function relationships of agents that reverse the resistance to ciprofloxacin.
在本研究中,对六氢喹啉衍生物的3-烷基酯和3-芳基酯进行了筛选,以评估它们降低细菌对环丙沙星(CAS 85721-33-1)耐药性的能力,环丙沙星被广泛用于治疗细菌感染。合成了一组在4位被2-芳基噻唑取代的六氢喹啉衍生物的3-烷基酯和3-芳基酯。针对耐环丙沙星的金黄色葡萄球菌临床菌株,评估了这些新合成化合物对环丙沙星抗菌活性的增强作用。采用琼脂平板扩散法测定不同合成化合物在有无环丙沙星存在时的抗菌活性。这些结果表明,六氢喹啉衍生物的两种3-烷基酯(7b-3和7b-4)增强了环丙沙星的抗菌效果。7b-4对环丙沙星抗菌活性的增强作用大于化合物7b-3。与其他合成化合物相比,7b-4在添加环丙沙星的平板上显示出抑菌圈增大了5.61倍。结果表明,化合物7b(3和4)可作为有价值的探针,用于研究逆转对环丙沙星耐药性的药物的构效关系。