[en] Benzothiazole is a privileged scaffold in medicinal chemistry present in diverse bioactive compounds with multiple pharmacological applications such as analgesic, anticonvulsant, antidiabetic, anti-inflammatory, anticancer and radioactive amyloidal imagining agents. We reported in this work the study of sixteen functionalized 2-aryl and 2-pyridinylbenzothiazoles as antimicrobial agents and as aryl hydrocarbon receptor (AhR) modulators. The antimicrobial activity against Gram-positive (S. aureus and M. luteus) and Gram-negative (P. aeruginosa, S. enterica and E. coli) pathogens yielded MIC ranging from 3.13 to 50 μg/mL and against the yeast C. albicans, the benzothiazoles displayed MIC from 12.5 to 100 μg/mL. All compounds showed promising antibiofilm activity against S. aureus and P. aeruginosa. The arylbenzothiazole 12 displayed the greatest biofilm eradication in S. aureus (74%) subsequently verified by fluorescence microscopy. The ability of benzothiazoles to modulate AhR expression was evaluated in a cell-based reporter gene assay. Six benzothiazoles (7, 8-10, 12, 13) induced a significant AhR-mediated transcription and interestingly compound 12 was also the strongest AhR-agonist identified. Structure-activity relationships are suggested herein for the AhR-agonism and antibiofilm activities. Furthermore, in silico predictions revealed a good ADMET profile and druglikeness for the arylbenzothiazole 12 as well as binding similarities to AhR compared with the endogenous agonist FICZ.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Goya-Jorge, Elizabeth ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Gestion de la qualité dans la chaîne alimentaire
Abdmouleh, Fatma; Conservatoire National des Arts et Métiers (Cnam) > Equipe de Chimie Moléculaire du Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (EA 7528),
Carpio, Laureano E; ProtoQSAR SL
Giner, Rosa M; University of Valencia > Department of Pharmacology > Professor
Veitía, Maité Sylla-Iyarreta; Conservatoire National des Arts et Métiers (Cnam) > Equipe de Chimie Moléculaire du Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (EA 7528) > Professor
Language :
English
Title :
Discovery of 2-aryl and 2-pyridinylbenzothiazoles endowed with antimicrobial and aryl hydrocarbon receptor agonistic activities
H2020 - 722634 - PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication.
Name of the research project :
protected - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication
Funders :
EC - European Commission EU - European Union
Funding number :
722634
Funding text :
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722634.
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