Novel 1,2,3‐triazolo phosphonate derivatives as potential antibacterial agents

Abstract

We describe the synthesis, characterization, and in vitro antibacterial evaluation of a library of novel compounds based on 1,2,3‐triazolo phosphonate framework along with the evaluation of DNA gyrase inhibitory potential of a promising molecule in silico. Preparation of these compounds was carried out via a multistep sequence comprising of the Abramov reaction followed by the Cu(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) as the key steps. Various α‐hydroxyphosphonate derivatives containing either a secondary or tertiary alcohol at the α position were prepared. When screened for their antibacterial activities in vitro using a Gram‐positive (Staphylococcus aureus) and three Gram‐negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) strains, majority of these derivatives exhibited reasonable to good effects with the analogue 5k being active against all the strains. The SAR analysis indicated that the activity was influenced by the position of the α‐hydroxyphosphonate moiety as well as the substituent present on the benzene ring attached to the 1,2,3‐triazole ring. Moreover, the compound 5k showed strong interactions with the DNA active site when docked into the DNA gyrase in silico. Thus, the 1,2,3‐triazolo phosphonate derivative 5k appeared to be a novel and promising hit molecule that deserves further study as a potential antibacterial agent.