巯基乙酸酯硫酯及其水解产物巯基乙酸共同抑制金属β-内酰胺酶L1。
Mercaptoacetate thioesters and their hydrolysate mercaptoacetic acids jointly inhibit metallo-β-lactamase L1.
作者信息
Chen Cheng, Xiang Yang, Liu Ya, Hu Xiangdong, Yang Ke-Wu
机构信息
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education , Innovation Laboratory of Chemical Biology , College of Chemistry and Materials Science , Northwest University , Xi'an 710127 , P. R. China . Email:
出版信息
Medchemcomm. 2018 May 17;9(7):1172-1177. doi: 10.1039/c8md00091c. eCollection 2018 Jul 1.
The 'superbug' infection caused by metallo-β-lactamases (MβLs) including L1 has grown into an emerging threat. To probe whether mercaptoacetate thioesters inhibiting L1 is a contribution of the thioester itself or its hydrolysate, ten mercaptoacetate thioesters were synthesized, which specifically inhibited L1, exhibiting IC values ranging from 0.17 to 1.2 μM, and was found to be the best inhibitor (IC = 0.17 μM). These thioesters restored the antimicrobial activity of cefazolin against expressing L1 by 2-4-fold. UV-vis monitoring showed that , and were unhydrolyzed in Tris buffer (pH 6.0-8.5), but hydrolyzed by L1; further HPLC monitoring indicated that 1/3 of the thioester was converted to mercaptoacetic acid. STD-NMR monitoring suggested that both the thioester and its hydrolysate mercaptoacetic acid jointly inhibited L1.
由包括L1在内的金属β-内酰胺酶（MβLs）引起的“超级细菌”感染已成为一种新出现的威胁。为探究巯基乙酸硫酯对L1的抑制作用是硫酯本身还是其水解产物的作用，合成了十种巯基乙酸硫酯，它们能特异性抑制L1，IC值范围为0.17至1.2μM，其中 被发现是最佳抑制剂（IC = 0.17μM）。这些硫酯使头孢唑林对表达L1的菌株的抗菌活性恢复了2至4倍。紫外可见监测表明， 在Tris缓冲液（pH 6.0 - 8.5）中未水解，但会被L1水解；进一步的高效液相色谱监测表明，三分之一的硫酯 转化为巯基乙酸。STD-NMR监测表明，硫酯及其水解产物巯基乙酸共同抑制L1。
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