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

Abstract

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.

1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

“…Structure‐activity relationship revealed that the presence of phenylacetamide next to triazole nucleus proved to be most efficient and the substitution of phenyl ring at that place deceases the activity. The phenyl ring with the methyl substitution or no substitution was equi‐potent [33] . Similarly, Kaushik et al .…”

“…The phenyl ring with the methyl substitution or no substitution was equi-potent. [33] Similarly, [34] (Figure 2).…”

Synthesis, structural characterization and antibacterial activity evaluation of novel quinolone-1,2,3-triazole-benzimidazole hybrids

“…2-Quinolones and their analogues are important nitrogen-containing heterocycles, widely present in nature as alkaloids (such as Viridicatol or Viridicatin (Fig. 1)) [5][6][7][8] and possess an extensive spectrum of biological properties among which is the antimicrobial [9,10]. Many of the quinolone-based scaffolds with antibacterial activity, were found to act mainly by inhibiting the activity of bacteria type II topoisomerase (DNA gyrase) or type IV topoisomerase [11].…”

Synthesis and In Silico Evaluation of Some New 2,4-Disubstituted Thiazole Derivatives

“…According to previous studies, DNA gyrase inhibition by thiazole derivatives was investigated and obtained remarkable enzyme inhibition results, even against drug-resistance pathogens [21][22][23]. The action mechanism of the DNA gyrase enzyme is need ATP energy.…”