Inhibition of Nonessential Bacterial Targets : Discovery of a Novel Serine O-Acetyltransferase Inhibitor

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http://hdl.handle.net/10138/326416

Lähdeviite

Pinto de Magalhães , J , Franko , N , Raboni , S , Annunziato , G , Tammela , P , Bruno , A , Bettati , S , Mozzarelli , A , Pieroni , M , Cambanini , B & Costantino , G 2020 , ' Inhibition of Nonessential Bacterial Targets : Discovery of a Novel Serine O -Acetyltransferase Inhibitor ' , ACS Medicinal Chemistry Letters , vol. 11 , no. 5 , pp. 790-797 . https://doi.org/10.1021/acsmedchemlett.9b00627

Julkaisun nimi: Inhibition of Nonessential Bacterial Targets : Discovery of a Novel Serine O-Acetyltransferase Inhibitor
Tekijä: Pinto de Magalhães, Joana; Franko, Nina; Raboni, Samanta; Annunziato, Giannamaria; Tammela, Päivi; Bruno, Agostino; Bettati, Stefano; Mozzarelli, Andrea; Pieroni, Marco; Cambanini, Barbara; Costantino, Gabriele
Tekijän organisaatio: Division of Pharmaceutical Biosciences
Drug Research Program
Bioactivity Screening Group
University Management
Päiväys: 2020-05-14
Kieli: eng
Sivumäärä: 8
Kuuluu julkaisusarjaan: ACS Medicinal Chemistry Letters
ISSN: 1948-5875
DOI-tunniste: https://doi.org/10.1021/acsmedchemlett.9b00627
URI: http://hdl.handle.net/10138/326416
Tiivistelmä: In Upsilon-proteobacteria and Actinomycetales, cysteine biosynthetic enzymes are indispensable during persistence and become dispensable during growth or acute infection. The biosynthetic machinery required to convert inorganic sulfur into cysteine is absent in mammals; therefore, it is a suitable drug target. We searched for inhibitors of Salmonella serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The virtual screening of three ChemDiv focused libraries containing 91 243 compounds was performed to identify potential SAT inhibitors. Scaffold similarity and the analysis of the overall physicochemical properties allowed the selection of 73 compounds that were purchased and evaluated on the recombinant enzyme. Six compounds displaying an IC50
Avainsanat: Adjuvant therapies
Antimicrobial resistance
CARBOXYLIC-ACIDS
COMPLEX
Cysteine biosynthesis
ESCHERICHIA-COLI
KINETIC MECHANISM
L-CYSTEINE
Nonessential targets
PURIFICATION
Serine acetyltransferase
317 Pharmacy
116 Chemical sciences
11832 Microbiology and virology
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: unspecified
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: acceptedVersion


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