LEGO-inspired drug design: unveiling a class of Benzo[d]thiazoles containing a 3,4-Dihydroxyphenyl moiety as plasma membrane H+-ATPase inhibitors
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LEGO-inspired drug design : unveiling a class of Benzo[d]thiazoles containing a 3,4-Dihydroxyphenyl moiety as plasma membrane H+-ATPase inhibitors. / Thanh Tung, Truong; Dao, Trong Tuan; Grifell Junyent, Marta; Palmgren, Michael Broberg; Günther-Pomorski, Thomas; Fuglsang, Anja Thoe; Christensen, Søren Brøgger; Nielsen, John.
I: ChemMedChem, Bind 13, Nr. 1, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - LEGO-inspired drug design
T2 - unveiling a class of Benzo[d]thiazoles containing a 3,4-Dihydroxyphenyl moiety as plasma membrane H+-ATPase inhibitors
AU - Thanh Tung, Truong
AU - Dao, Trong Tuan
AU - Grifell Junyent, Marta
AU - Palmgren, Michael Broberg
AU - Günther-Pomorski, Thomas
AU - Fuglsang, Anja Thoe
AU - Christensen, Søren Brøgger
AU - Nielsen, John
PY - 2018
Y1 - 2018
N2 - The fungal plasma membrane H+-ATPase(Pma1p)isapotential target for the discovery of new antifungal agents. Surprisingly,nostructure–activity rela tionship studies for small molecules targeting Pma1p have been reported. Herein, we disclose aLEGO-inspired fragmentassembly strategy for the design,synthesis, and discovery of benzo[d]thiazoles containing a3,4-dihydroxyphenyl moiety as potentialPma1p inhibitors. Aseries of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 mm in an in vitro plasma memb rane H+-ATPase assay.These compounds were also found to strongly inhibit the action of proton pumpingwhen Pma1p was reconstituted into liposomes. 1-(3,4-ihydroxyphenyl)-2-((6-(trifluoromethyl)-benzo[d]thiazol-2-yl)thio)ethan-one(compound 38)showed inhibitory activities on the growth of Candida albicans and Saccharomyces cerevisiae ,which could be correlated andsubstantiated with the ability to inhibitPma1p in vitro.
AB - The fungal plasma membrane H+-ATPase(Pma1p)isapotential target for the discovery of new antifungal agents. Surprisingly,nostructure–activity rela tionship studies for small molecules targeting Pma1p have been reported. Herein, we disclose aLEGO-inspired fragmentassembly strategy for the design,synthesis, and discovery of benzo[d]thiazoles containing a3,4-dihydroxyphenyl moiety as potentialPma1p inhibitors. Aseries of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 mm in an in vitro plasma memb rane H+-ATPase assay.These compounds were also found to strongly inhibit the action of proton pumpingwhen Pma1p was reconstituted into liposomes. 1-(3,4-ihydroxyphenyl)-2-((6-(trifluoromethyl)-benzo[d]thiazol-2-yl)thio)ethan-one(compound 38)showed inhibitory activities on the growth of Candida albicans and Saccharomyces cerevisiae ,which could be correlated andsubstantiated with the ability to inhibitPma1p in vitro.
U2 - 10.1002/cmdc.201700635
DO - 10.1002/cmdc.201700635
M3 - Journal article
C2 - 29139202
VL - 13
JO - Farmaco
JF - Farmaco
SN - 1860-7179
IS - 1
ER -
ID: 188125452