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Design, Synthesis, in vitro and in silico Characterization of 2‐Quinolone‐L‐alaninate‐1,2,3‐triazoles as Antimicrobial Agents
Author(s) -
Moussaoui Oussama,
Bhadane Rajendra,
Sghyar Riham,
Ilaš Janez,
El Hadrami El Mestafa,
Chakroune Said,
SaloAhen Outi M. H.
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100714
Subject(s) - quinolone , antimicrobial , chemistry , combinatorial chemistry , dna gyrase , moiety , in silico , pharmacophore , stereochemistry , antibacterial activity , in vitro , triazole , antibiotics , organic chemistry , biochemistry , escherichia coli , bacteria , biology , gene , genetics
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.