Confronting Tuberculosis: A Synthetic Quinoline-Isonicotinic Acid Hydrazide Hybrid Compound as a Potent Lead Molecule Against Mycobacterium tuberculosis
Rattachement africain : in. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The current tuberculosis (TB) treatment is challenged by a complex first-line treatment for drug-sensitive (DS) TB. Additionally, the prevalence of multidrug (MDR)- and extensively drug (XDR)-resistant TB necessitates the search for new drug prototypes. We synthesized and screened 30 hybrid compounds containing aminopyridine and 2-chloro-3-formyl quinoline to arrive at a compound with potent antimycobacterial activity, UH-NIP-16. Subsequently, antimycobacterial activity against DS and MDR Mycobacterium tuberculosis ( M.tb ) strains were performed. It demonstrated an MIC 50 value of 1.86 ± 0.21 μM for laboratory pathogenic M.tb strain H37Rv and 3.045 ± 0.813 μM for a clinical M.tb strain CDC1551. UH-NIP-16 also decreased the MIC 50 values of streptomycin, isoniazid, ethambutol, and bedaquiline to about 45, 55, 68, and 76%, respectively, when used in combination, potentiating their activities. The molecule was active against a clinical MDR M.tb strain. Cytotoxicity on PBMCs from healthy donors and on human cell lines was found to be negligible. Further, blind docking of UH-NIP-16 using Auto Dock Vina and MGL tools onto diverse M.tb proteins showed high binding affinities with multiple M.tb proteins, the top five targets being metabolically critical proteins CelA1, DevS, MmaA4, lysine acetyltransferase, and immunity factor for tuberculosis necrotizing toxin. These bindings were confirmed by fluorescence spectroscopy using a representative protein, MmaA4. Envisaging that a pathogen will have a lower probability of developing resistance to a hybrid molecule with multiple targets, we propose that UH-NIP-16 can be further developed as a lead molecule with the bacteriostatic potential against M.tb, both alone and in combination with first-line drugs.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Confronting Tuberculosis: A Synthetic Quinoline-Isonicotinic Acid Hydrazide Hybrid Compound as a Potent Lead Molecule Against <i>Mycobacterium tuberculosis</i>
- Date Crossref
- 08/05/2024
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
University of Hyderabad pays non établi dans la noticeUniversité ou école supérieure
-
Savitribai Phule Pune University Bioinformatics Centre pays non établi dans la noticeUniversité ou école supérieure
-
National Institute of Pharmaceutical Education and Research Department of Medicinal Chemistry pays non établi dans la noticeUniversité ou école supérieure
-
National Centre for Cell Science pays non établi dans la noticeStructure de recherche
-
School of Life Sciences Laboratory of Molecular Pathogenesis pays non établi dans la noticeUniversité ou école supérieure
-
ICMR-National Institute for Translational Virology and AIDS Research Molecular Biology Division pays non établi dans la noticeStructure de recherche
University of Hyderabad, Bioinformatics Centre — Savitribai Phule Pune University et Department of Medicinal Chemistry — National Institute of Pharmaceutical Education and Research, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.