Bioorganic and Medicinal Chemistry Letters p. 637 - 641 (2018)
Update date:2022-07-29
Topics:
Mori, Mattia
Deodato, Davide
Kasula, Mohan
Ferraris, Davide M.
Sanna, Adriana
De Logu, Alessandro
Rizzi, Menico
Botta, Maurizio
Sixteen 3-(carboxymethyl)rhodanines, and twelve aminothiazoles as rhodanine-mimetics were designed, synthesized and tested as inhibitors of the Zmp1 enzyme from Mycobacterium tuberculosis (Mtb). Almost all rhodanines (5a–d, 5f–n, and 7a–b) exhibited Zmp1 inhibition with IC50 values in the range 1.3–43.9 μM, whereas only aminothiazoles 12b and 12d proved active with IC50 values of 41.3 and 35.7 μM, respectively. Structure-activity relationships (SAR) were coupled with molecular modeling studies to highlight structural determinants for Zmp1 inhibition. Moreover, rhodanines 5a and 5c induced 23.4 and 53.8% of Mtb growth inhibition in THP-1 infected cells, respectively, at the non-toxic concentration of 10 μg/ml. This work represents a step forward in targeting Zmp1 by small molecules.
View Morewebsite:http://www.arromax.com
Contact:+86-0512-62959601 skype:aimmezhang
Address:Suite 401, Bldg A3, 218 Xinghu St.Suzhou Industrial Park 215123, P.R. China
Yurui(Shanghai)Chemical Co.,Ltd
Contact:0086 21-50456736
Address:No.3188 Xiupu Road,Shanghai
Junkai (Tianjin) Chemical Co., Ltd.
website:http://www.junkaichem.com
Contact:86-22-85689515
Address:Room 8-501, Building K2, The Hi-Tech Green Industrial Base, No.6, 6th Road, Hi-Tech Development Road, Tianjin Hi-Tech IndustrialPark, Tianjin, China.
website:http://www.maisonchem.com.cn
Contact:0086-311-83833777
Address:Leitou industrial district, xinji, shijiazhuang city, hebei province,
Contact:+86-577-65618087-605
Address:Room 402, Unit 4 Xinhu Bldg. Waitan Ruian City, Zhejiang China.
Doi:10.1246/bcsj.59.1656
(1986)Doi:10.1021/jacs.1c00564
(2021)Doi:10.1007/BF00599260
(1986)Doi:10.1039/jr9380002119
(1938)Doi:10.1039/jr9340001524
(1934)Doi:10.1021/ja01306a054
(1935)