Design, Synthesis, in vitro and in silico Characterization of 2-Quinolone-L-alaninate-1,2,3-triazoles as Antimicrobial Agents.

Autor: Moussaoui O; Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, 30000, Fez, Morocco., Bhadane R; Structural Bioinformatics Laboratory, Biochemistry, Åbo Akademi University, 20520, Turku, Finland.; Pharmaceutical Sciences Laboratory, Pharmacy, Åbo Akademi University, 20520, Turku, Finland., Sghyar R; Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, 30000, Fez, Morocco., Ilaš J; Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia., El Hadrami EM; Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, 30000, Fez, Morocco., Chakroune S; Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, 30000, Fez, Morocco., Salo-Ahen OMH; Structural Bioinformatics Laboratory, Biochemistry, Åbo Akademi University, 20520, Turku, Finland.; Pharmaceutical Sciences Laboratory, Pharmacy, Åbo Akademi University, 20520, Turku, Finland.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2022 Mar 04; Vol. 17 (5), pp. e202100714. Date of Electronic Publication: 2022 Jan 27.
DOI: 10.1002/cmdc.202100714
Abstrakt: Due to the ever-increasing antimicrobial resistance there is an urgent need to continuously design and develop novel antimicrobial agents. Inspired by the broad antibacterial activities of various heterocyclic compounds such as 2-quinolone derivatives, we designed and synthesized new methyl-(2-oxo-1,2-dihydroquinolin-4-yl)-L-alaninate-1,2,3-triazole derivatives via 1,3-dipolar cycloaddition reaction of 1-propargyl-2-quinolone-L-alaninate with appropriate azide groups. The synthesized compounds were obtained in good yield ranging from 75 to 80 %. The chemical structures of these novel hybrid molecules were determined by spectroscopic methods and the antimicrobial activity of the compounds was investigated against both bacterial and fungal strains. The tested compounds showed significant antimicrobial activity and weak to moderate antifungal activity. Despite the evident similarity of the quinolone moiety of our compounds with fluoroquinolones, our compounds do not function by inhibiting DNA gyrase. Computational characterization of the compounds shows that they have attractive physicochemical and pharmacokinetic properties and could serve as templates for developing potential antimicrobial agents for clinical use.
(© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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