Investigation of new 1,2,3-triazolyl-quinolinyl-propan-2-ol derivatives as potential antimicrobial agents: in vitro and in silico approach

A new series of 1-((1-(4-substituted benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol (9a-x) have been synthesized. The newly synthesized 1,2,3-triazolyl-quinolinyl-propan-2-ol (9a-x) derivatives were screened for in vitro antimicrobial activity against M. tuberculos...

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Published in:Journal of biomolecular structure & dynamics 2024-02, Vol.42 (3), p.1191-1207
Main Authors: Shinde, Abhijit D., Nandurkar, Yogesh M., Bhalekar, Swapnil, Walunj, Yogesh S., Ugale, Sandip, Ahmad, Iqrar, Patel, Harun, Chavan, Abhijit P., Mhaske, Pravin C.
Format: Article
Language:English
Subjects:
2-Propanol
3-Triazole
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents - pharmacology
antimicrobial activity
antitubercular activity
Antitubercular Agents - pharmacology
cytotoxicity activity
DNA Gyrase - metabolism
Escherichia coli - metabolism
Humans
Microbial Sensitivity Tests
molecular docking
Molecular Docking Simulation
Mycobacterium tuberculosis - metabolism
Quinolinyl-propan-2-ol
Staphylococcus aureus
Tuberculosis
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Summary:A new series of 1-((1-(4-substituted benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol (9a-x) have been synthesized. The newly synthesized 1,2,3-triazolyl-quinolinyl-propan-2-ol (9a-x) derivatives were screened for in vitro antimicrobial activity against M. tuberculosis H37Rv, E. coli, P. mirabilis, B. subtilis, and S. albus. Most of the compounds showed good to moderate antibacterial activity and all derivatives have shown excellent to good antitubercular activity with MIC 0.8-12.5 μg/mL. To know the plausible mode of action for antibacterial activity the docking study against DNA gyrase from M. tuberculosis and S. aureus was investigated. The compounds have shown significant docking scores in the range of −9.532 to −7.087 and −9.543 to −6.621 Kcal/mol with the DNA gyrase enzyme of S. aureus (PDB ID: 2XCT) and M. tuberculosis (PDB ID: 5BS8), respectively. Against the S. aureus and M. tuberculosis H37Rv strains, the compound 9 l showed good activity with MIC values of 62.5 and 3.33 μM. It also showed significant docking scores in both targets with −8.291 and −8.885 Kcal/mol, respectively. Molecular dynamics was studied to investigate the structural and dynamics transitions at the atomistic level in S. aureus DNA gyrase (2XCT) and M. tuberculosis DNA gyrase (5BS8). The results revealed that the residues in the active binding pockets of the S. aureus and M. tuberculosis DNA gyrase proteins that interacted with compound 9 l remained relatively consistent throughout the MD simulations and thus, reflected the conformation stability of the respective complexes. Thus, the significant antimicrobial activity of derivatives 9a-x recommended that these compounds could assist in the development of lead compounds to treat for bacterial infections. Communicated by Ramaswamy H. Sarma
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2023.2217922