Introduction: The escalating threat due to dwindling effect of antibiotics and challenge
of tackling rising drug-resistant infections has gathered high focus in current medicinal research.
Methods: In an attempt to find new molecules that can defeat microbial resistance, two new series
of 2-[2-substituted ethenyl]-5-(substituted methoxy)-1,3,4-oxadiazole derivatives were synthesized.
Various aromatic hydrazides were allowed to undergo cyclization to substituted oxadiazole-2-
amines in the presence of cyanogen bromide and further condensed with different heterocyclic aldehydes
to give new oxadiazole derivatives. The synthesized molecules were fully characterized by
various spectral techniques and tested for antimicrobial activity.
Results: Almost all the newly synthesized compounds especially (5g-5l) displayed remarkable
growth inhibition against three bacterial strains: M. smegmatis, S. aureus, E. coli and fungi C. albicans.
The antimicrobial activity was further confirmed by MIC assay against the same microorganisms.
Oxadiazole 5g displayed promising activity with a MIC value of 0.025 mM for two bacteria
and fungi, whereas MIC of this compound for E. coli was 0.1 mM. Other active compounds (5h-5l)
also exhibited good MIC ranging between 0.313 to 5.0 mM against the selected microorganisms.
Docking simulations were generated to explore the potential binding approaches of ligand 5g at the
D-alanine:d-alanine ligase (Ddl) protein of E. coli and S. aureus.
Conclusion: Molecule 5g was active even at a lower concentration and could probably act as a
prospective lead molecule for targeting the drug resistant microorganisms.