可溶性9-溴取代中氮茚并喹啉-5,12-二酮衍生物的合成及其抗菌活性
Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives.
作者信息
Yang Hui, Wang Hao-Wen, Zhu Teng-Wei, Yu Le-Mao, Chen Jian-Wen, Wang Lu-Xia, Shi Lei, Li Ding, Gu Lian-Quan, Huang Zhi-Shu, An Lin-Kun
机构信息
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Department of Clinical Laboratory, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
出版信息
Eur J Med Chem. 2017 Feb 15;127:166-173. doi: 10.1016/j.ejmech.2016.12.054. Epub 2016 Dec 27.
In our previous research, 9-bromo indolizinoquinoline-5,12-dione 1 has been found to be a good anti-MRSA agent. However, it had very low bioavailability in vivo possibly due to its low solubility in water. In order to obtain the derivatives with higher anti-MRSA activity and good water solubility, twenty eight bromo-substituted indolizinoquinoline-5,12-dione derivatives were synthesized in the present study. The antibacterial activity of the synthesized compounds was evaluated against one gram-negative and some gram-positive bacterial strains including 100 clinical MRSA strains. The UV assays were carried out to determine the solubility of six active compounds 16, 21, 23 and 27-29. The most potent compound 28 exhibited strong activity against clinical MRSA strains with both MIC and MIC values lower than 7.8 ng/mL. Compound 27 had good water solubility of 1.98 mg/mL and strong activity against clinical MRSA strains with MIC value of 63 ng/mL and MIC value of 125 ng/mL, 16-fold higher than that of Vancomycin.
在我们之前的研究中，已发现9-溴中氮茚并喹啉-5,12-二酮1是一种良好的抗耐甲氧西林金黄色葡萄球菌（MRSA）药物。然而，其体内生物利用度非常低，可能是由于其在水中的溶解度低。为了获得具有更高抗MRSA活性和良好水溶性的衍生物，本研究合成了28种溴代中氮茚并喹啉-5,12-二酮衍生物。对合成的化合物针对1种革兰氏阴性菌和一些革兰氏阳性菌菌株（包括100株临床MRSA菌株）进行了抗菌活性评估。进行了紫外测定以确定6种活性化合物16、21、23以及27 - 29的溶解度。最有效的化合物28对临床MRSA菌株表现出强活性，其最低抑菌浓度（MIC）和最低杀菌浓度（MBC）值均低于7.8 ng/mL。化合物27具有1.98 mg/mL的良好水溶性，并且对临床MRSA菌株具有强活性，其MIC值为63 ng/mL，MBC值为125 ng/mL，比万古霉素高16倍。
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