Academic Journal
Exploring the Antitubercular Activity of Anthranilic Acid Derivatives: From MabA (FabG1) Inhibition to Intrabacterial Acidification
| العنوان: | Exploring the Antitubercular Activity of Anthranilic Acid Derivatives: From MabA (FabG1) Inhibition to Intrabacterial Acidification |
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| المؤلفون: | Faïon, Léo, Djaout, Kamel, Pintiala, Catalin, Piveteau, Catherine, Leroux, Florence, Biela, Alexandre, Slupek, Stéphanie, Antoine, Rudy, Záhorszká, Monika, Cantrelle, Francois-Xavier, Hanoulle, Xavier, Korduláková, Jana, Deprez, Benoit, Willand, Nicolas, Baulard, Alain, Flipo, Marion |
| المساهمون: | Médicaments et molécules pour les systèmes vivants - U 1177 (M2SV), Institut Pasteur de Lille, Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Comenius University in Bratislava, Biologie Structurale Intégrative (ERL 9002 - INSERM U1167 - BSI), Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), ANR-20-PAMR-0005,Mustart,Multiparametric Strategies against Antibiotic Resistance in Tuberculosis(2020) |
| المصدر: | ISSN: 1424-8247 ; Pharmaceuticals ; https://hal.science/hal-04007450 ; Pharmaceuticals, 2023, 16 (3), pp.335. ⟨10.3390/ph16030335⟩. |
| بيانات النشر: | CCSD MDPI |
| سنة النشر: | 2023 |
| المجموعة: | LillOA (HAL Lille Open Archive, Université de Lille) |
| مصطلحات موضوعية: | anthranilic acid, FabG1, tuberculosis, mycolic acids, MabA inhibitors, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
| الوصف: | International audience ; Mycobacterium tuberculosis, the pathogen that causes tuberculosis, is responsible for the death of 1.5 million people each year and the number of bacteria resistant to the standard regimen is constantly increasing. This highlights the need to discover molecules that act on new M. tuberculosis targets. Mycolic acids, which are very long-chain fatty acids essential for M. tuberculosis viability, are synthesized by two types of fatty acid synthase (FAS) systems. MabA (FabG1) is an essential enzyme belonging to the FAS-II cycle. We have recently reported the discovery of anthranilic acids as MabA inhibitors. Here, the structure–activity relationships around the anthranilic acid core, the binding of a fluorinated analog to MabA by NMR experiments, the physico-chemical properties and the antimycobacterial activity of these inhibitors were explored. Further investigation of the mechanism of action in bacterio showed that these compounds affect other targets than MabA in mycobacterial cells and that their antituberculous activity is due to the carboxylic acid moiety which induces intrabacterial acidification. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.3390/ph16030335 |
| الاتاحة: | https://hal.science/hal-04007450 https://hal.science/hal-04007450v1/document https://hal.science/hal-04007450v1/file/pharmaceuticals-16-00335-v2.pdf https://doi.org/10.3390/ph16030335 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.FD89D4FE |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ph16030335 |
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