Identification of natural potent inhibitors against Mycobacterium tuberculosis isocitrate lyase: an in silico study.
Drug discovery
Flavonoids
Isocitrate Lyase
MD simulation
Mycobacterium tuberculosis
Journal
Molecular diversity
ISSN: 1573-501X
Titre abrégé: Mol Divers
Pays: Netherlands
ID NLM: 9516534
Informations de publication
Date de publication:
14 Aug 2023
14 Aug 2023
Historique:
received:
29
03
2023
accepted:
02
08
2023
medline:
14
8
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
aheadofprint
Résumé
Tuberculosis (TB) is a global burden to humanity due to its adverse effects on health and society since time is not clearly defined. The existence of drug-resistant strains and the potential threat posed by latent tuberculosis act as strong impetuses for developing novel anti-tuberculosis drugs. In this study, various flavonoids were tested against the Mycobacterium tuberculosis (Mtb) Isocitrate Lyase (ICL), which has been identified as an authorised therapeutic target for treating Mtb infection. Using in silico drug discovery approach, a library of 241 flavonoid compounds was virtually screened against the binding pocket of the crystalline ligand, the VGX inhibitor, in the Mtb ICL protein. As a result, the top four flavonoids were selected based on binding score and were further considered for redocking and intermolecular contact profiling analysis. The global and local fluctuations in the protein and ligand structure were analysed using their root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values obtained from the GROMACS generated 100 ns molecular dynamics (MD) simulation trajectories. The end-state binding free energy was also calculated using the MMPBSA approach for all the respective docked complexes. All four selected compounds exhibited considerable stability and affinity compared to control ligands, i.e. VGX inhibitor; however, Vaccarin showed the highest stability and affinity against the Mtb ICL protein active site, followed by the Genistin, Glabridin, and Corylin. Therefore, this study recommends selected flavonoids for in vitro and in vivo experimental studies to check their potency and efficacy against Mtb.
Identifiants
pubmed: 37578620
doi: 10.1007/s11030-023-10711-w
pii: 10.1007/s11030-023-10711-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Prince Sattam bin Abdulaziz University
ID : PSAU/2023/R/1444
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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