TY - JOUR
T1 - New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents
AU - Chiarelli, Laurent R.
AU - Mori, Matteo
AU - Beretta, Giangiacomo
AU - Gelain, Arianna
AU - Pini, Elena
AU - Sammartino, Josè Camilla
AU - Stelitano, Giovanni
AU - Barlocco, Daniela
AU - Costantino, Luca
AU - Lapillo, Margherita
AU - Poli, Giulio
AU - Caligiuri, Isabella
AU - Rizzolio, Flavio
AU - Bellinzoni, Marco
AU - Tuccinardi, Tiziano
AU - Villa, Stefania
AU - Meneghetti, Fiorella
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K i of 8.8 µM and its antimycobacterial activity (MIC 99 = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.
AB - Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K i of 8.8 µM and its antimycobacterial activity (MIC 99 = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.
KW - antimycobacterial agent
KW - drug design
KW - molecular modelling
KW - mycobactins
KW - siderophores
KW - Tuberculosis
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U2 - 10.1080/14756366.2019.1589462
DO - 10.1080/14756366.2019.1589462
M3 - Article
C2 - 30889995
AN - SCOPUS:85063209816
VL - 34
SP - 823
EP - 828
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
SN - 1475-6366
IS - 1
ER -