MoS2-Calix[4]arene Catalyzed Synthesis and Molecular Docking Study of 2,4,5-Trisubstituted Imidazoles As Potent Inhibitors of Mycobacterium tuberculosis.
ACS Comb Sci
; 22(10): 509-518, 2020 10 12.
Article
in En
| MEDLINE
| ID: mdl-32806898
ABSTRACT
A MoS2-supported-calix[4]arene (MoS2-CA4) nanocatalyst was used for efficient synthesis of 2,4,5-trisubstituted imidazole derivatives from 1-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione, aldehydes and ammonium acetate under solvent-free conditions. Reusability of the catalyst up to five cycles without any significant loss in the yields of the product is the unique feature of this heterogeneous solid catalysis. Furthermore, the noteworthy highlights of this method are safe reaction profiles, broad substrate scope, excellent yields, economical, solvent-free, and simple workup conditions. All synthesized compounds were evaluated for their in vitro antitubercular (TB) activity against Mycobacterium tuberculosis (Mtb) H37Rv. Among the screened compounds 3c, 3d, 3f, 3m, and 3r had MIC values of 2.15, 2.78, 5.75, 1.36, and 0.75 µM, respectively, and exhibited more potency than the reference drugs pyrazinamide (MIC 3.12 µM), ciprofloxacin (MIC 4.73 µM), and ethambutol (7.61 µM). Besides, potent compounds (3c, 3d, 3f, 3m, and 3r) have been tested for inhibition of MabA (ß-ketoacyl-ACP reductase) enzyme and cytotoxic activity against mammalian Vero cell line. A molecular docking study was carried out on the MabA (PDB ID 1UZN) enzyme to predict the interactions of the synthesized compounds. The results of the in vitro anti-TB activity and docking study showed that synthesized compounds have a strong anti-TB activity and can be adapted and produced more effectively as a lead compound.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenols
/
Bacterial Proteins
/
Calixarenes
/
Disulfides
/
Enzyme Inhibitors
/
3-Oxoacyl-(Acyl-Carrier-Protein) Reductase
/
Imidazoles
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Molybdenum
/
Mycobacterium tuberculosis
/
Antitubercular Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
ACS Comb Sci
Year:
2020
Document type:
Article
Affiliation country:
India