Abstract
In the current study, new bis(2,5-disubstituted 1,3,4-oxadiazoles) linked to aliphatic cores were efficiently prepared. For this purpose, the appropriate bis(aldehydes) and benzohydrazides were reacted to produce the corresponding bis(N-benzoylhydrazones). The oxidative cyclization of the previous intermediates was optimized using different reagents, solvents, and reaction temperatures. Three equivalents of chloramine-T in ethanol at 80 °C for 3 h produced good yields of the target bis(1,3,4-oxadiazoles). The antibacterial activity of new bis(1,3,4-oxadiazoles) was screened against six gram-positive and negative strains using ciprofloxacin as a reference (MIC values of 2.9 µM). Hybrids 4a and 4b showed the highest efficacy with MIC values of 7.3 and 7.2 µM against the Staphylococcus aureus strain, respectively, and 14.7 and 14.3 µM against the Pseudomonas aeruginosa strain. SwissADME, the drug-likeness model score, bioactivity scores, and molecular docking were also used to validate the activity of some new hybrids as potential antibacterial drugs and DNA gyrase inhibitors.