التفاصيل البيبلوغرافية
| العنوان: |
Arylamino containing hydroxamic acids as potent urease inhibitors for the treatment of Helicobacter pylori infection. |
| المؤلفون: |
Liu, Qi1, Shi, Wei-Kang1, Ren, Shen-Zhen2, Ni, Wei-Wei1, Li, Wei-Yi1, Chen, Hui-Min1, Liu, Pei1, Yuan, Jing1, He, Xiao-Su1, Liu, Jia-Jia1, Cao, Peng1, Yang, Pu-Zhen1, Xiao, Zhu-Ping1,2 xiaozhuping2005@163.com, Zhu, Hai-Liang1,2 zhuhl@nju.edu.cn |
| المصدر: |
European Journal of Medicinal Chemistry. Aug2018, Vol. 156, p126-136. 11p. |
| مصطلحات موضوعية: |
*HELICOBACTER pylori, *DRUG therapy, *ACIDS, *GRAM-negative bacteria, *CHEMISTRY |
| مستخلص: |
A novel series of aniline-containing hydroxamic acids were designed, synthesized and evaluated as anti-virulence agents for the treatment of gastritis and gastric ulcer caused by Helicobacter pylori . In vitro enzyme-based screen together with in vivo assays and structure−activity relationship (SAR) studies led to the discovery of three potent urease inhibitors 3-(3,5-dichlorophenylamino) N -hydroxypropanamide ( 3a ), 3-(2-chlorophenylamino) N -hydroxypropanamide ( 3d ) and 3-(2,4-dichlorophenylamino) N -hydroxypropanamide ( 3n ). Compounds 3a , 3d and 3n showed excellent urease inhibition with IC 50 values 0.043 ± 0.005, 0.055 ± 0.008 and 0.018 ± 0.002 μM, and significantly depressed gastritis developing at the dose of 32 mg/kg b. i.d with eradication rates of H. pylori reaching 92.3, 84.6 and 100%, respectively. Preliminary safety studies (acute toxicity in mice) disclosed that 3a , 3d and 3n was well-tolerated in KM mice with LD 50 s of 2982.8, 3349.4 and 3126.9 mg/kg, respectively. Collectively, the data obtained in this study indicate that 3a , 3d and 3n , in particular 3n , could considered as promising candidates for the potential treatment of H. pylori caused gastritis and gastric ulcer, and hence merit further studies. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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