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

Abstract

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

Keywords:

• Quinolinyl-propan-2-ol
• 1
• 2
• 3-Triazole
• antimicrobial activity
• antitubercular activity
• cytotoxicity activity
• molecular docking

Acknowledgments

ADS expresses his gratefulness to the CSIR-SRF fellowship for the financial support (File No.08/319(000 4)/2017-EMR-1). The authors would like to acknowledge S. P. Mandali Pune and Late. Dr. T. R. Ingale’s family for providing infrastructure facilities. The authors would like to thank CIF-SPPU, Pune for spectral analysis. S. P. Mandali’s Bhide Foundation Pune has been acknowledged for lending support to their biological activities.

Authors’ contribution

ADS, APC and PCM contributed to the study’s conception and design of the scheme and manuscript writing. ADS, SW, YMN, YSW, and SU contributed to the synthesis and purification of compounds, all authors contributed to the data collection and characterization of synthesized compounds. Molecular docking and MD simulation analysis and writing were performed by Iqrar Ahmad and Harun Patel.

Disclosure statement

There are no conflicts to declare.

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research, India.