friend or foe?
Matic Proj (Author), Martina Hrast (Author), Damijan Knez (Author), Krištof Bozovičar (Author), Katarina Grabrijan (Author), Anže Meden (Author), Stanislav Gobec (Author), Rok Frlan (Author)

Abstract

Thiazoles exhibit a wide range of biological activities and therefore represent useful and attractive building blocks. To evaluate their usefulness and pinpoint their liabilities in fragment screening campaigns, we assembled a focused library of 49 fragment-sized thiazoles and thiadiazoles with various substituents, namely amines, bromides, carboxylic acids, and nitriles. The library was profiled in a cascade of biochemical inhibition assays, redox activity, thiol reactivity, and stability assays. Our study indicates that when thiazole derivatives are identified as screening hits, their reactivity should be carefully addressed and correlated with specific on-target engagement. Importantly, nonspecific inhibition should be excluded using experimental approaches and in silico predictions. To help with validation of hits identified in fragment screening campaigns, we can apply our high-throughput profiling workflow to focus on the most tractable compounds with a clear mechanism of action.

Keywords

thiazoles;hit profiling;promiscuous compounds;frequent hitters;privileged scaffolds;fragments;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 547.78:615.4:54
COBISS: 130706947 Link will open in a new window
ISSN: 1948-5875
Views: 91
Downloads: 52
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Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: hit profiliranje;promiskuitetne spojine;pogosti napadalci;privilegirani odri;fragmenti;Tiazoli;Farmacevtska kemija;
Type (COBISS): Article
Pages: str. 1905–1910
Volume: ǂVol. ǂ13
Issue: ǂiss. ǂ12
Chronology: 2022
DOI: 10.1021/acsmedchemlett.2c00429
ID: 17361116