Journal of Medicinal Chemistry p. 6759 - 6778 (2018)
Update date:2022-08-15
Topics:
Sharma, Shiv K.
Yip, Christopher
Esposito, Emilio Xavier
Sharma, Prateek V.
Simon, Matthew P.
Abel-Santos, Ernesto
Firestine, Steven M.
Clostridium difficile infections (CDI), particularly those caused by the BI/NAP1/027 epidemic strains, are challenging to treat. One method to address this disease is to prevent the development of CDI by inhibiting the germination of C. difficile spores. Previous studies have identified cholic amide m-sulfonic acid, CamSA, as an inhibitor of spore germination. However, CamSA is inactive against the hypervirulent strain R20291. To circumvent this problem, a series of cholic acid amides were synthesized and tested against R20291. The best compound in the series was the simple phenyl amide analogue which possessed an IC50 value of 1.8 μM, more than 225 times as potent as the natural germination inhibitor, chenodeoxycholate. This is the most potent inhibitor of C. difficile spore germination described to date. QSAR and molecular modeling analysis demonstrated that increases in hydrophobicity and decreases in partial charge or polar surface area were correlated with increases in potency.
View MoreZhengzhou Yuanli Biological Technology Co., Ltd.
Contact:+86-371-67897870/67897895
Address:No. 38, Qingyang Street, Zhengzhou, Henan, China
Contact:13813902930 025-52714267
Address:20 Fengji Road, Yuhua Economic Development Zone, Nanjing, Jiangsu, P. R. China
Shanghai united Scientific Co.,Ltd.
Contact:+86-21-53535353
Address:28F No.900 huaihai Road Shanghai China
Contact:86-931-8272767
Address:Room 602, No.461, Nanchang Road, Chengguan District, Lanzhou City, China PRC
Tianjin Jiuri New Materials Co., Ltd.
Contact:+86-22-58889220
Address:C-5/6, Vison Hill, No.1 Gonghua Road, Huayuan Hi-tech Park, Tianjin, China.
Doi:10.1002/hlca.19780610728
(1978)Doi:10.1021/jo01313a050
(1980)Doi:10.1002/hlca.19780610828
(1978)Doi:10.1021/ja01260a013
(1942)Doi:10.1055/s-0033-1339693
(2013)Doi:10.1016/S0040-4039(00)97705-0
(1990)