New Oxadiazole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

Abstract

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.

Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative Against Candida albicans

“…Additionally, it is absent in humans, that can contribute with the development of selective drugs against pathogens [ 25 ]. 1,3,4-oxadiazole-based drugs have been widely studied by researchers [ 21 , 22 , 23 , 26 , 27 , 28 , 29 ]. These compounds have a high therapeutic power and broad spectrum of action, such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral activity, among others [ 29 ].…”

1,3,4‐oxadiazole derivatives as potential antimicrobial agents

“…Among all the studied derivatives, 147 showed the most potent antimicrobial activity (MIC = 25 μM) against S. aureus and C. albicans, which was comparable with the Ciprofloxacin (MIC <24 μM) and Fluconazole (MIC <24 μM). The SAR analysis revealed that quinoline containing 1,3,4‐oxadiazole compound ( 147 ) showed better activity than naphthalene containing 1,3,4‐oxadiazoles ( 148 – 153 , MIC >10) against studied microbial strains except E. coli (Dhara et al, 2018).…”