Development of Oxadiazole-Sulfonamide-Based Compounds as Potential Antibacterial Agents

Abstract

In this work, substituted 1,2,4-oxadiazoles (OX1− OX27) were screened against five bacterial strains, identified to be OX7 and OX11 as growth inhibitors with minimum inhibitory concentration (MIC) values of 31.25 and 15.75 μg/mL, respectively. The growth inhibitory property of OX7 and OX11 was further validated by disk diffusion, growth curve, and time kill curve assays. Both disrupted biofilm formation with 92−100% reduction examined by the XTT assay were further visualized by scanning electron microscopy analysis. These compounds in combination with ciprofloxacin also exhibit synergy against Escherichia coli cells. With insignificant cytotoxic behavior on HEK293 cells, human red blood cells, and Galleria mellonella larvae, OX11 was tested against 28 multidrug resistant environmental isolates of bacteria and showed inhibition of Kluyvera georgiana and Citrobacter werkmanii strains with 32 and 16 μg/mL MIC values, respectively. The synergistic behavior of OX11 with ampicillin showed many fold reductions in MIC values against K. georgiana and Klebsiella pneumoniae multidrug resistant strains. Further, transmission electron microscopy analysis of OX11-treated E. coli cells showed a significantly damaged cell wall, which resulted in the loss of integrity and cytosolic oozing. OX11 showed significant changes in the secondary structure of human serum albumin (HSA) in the presence of OX11, enhancing HSA stability. Overall, the study provided a suitable core for further synthetic alterations and development as an antibacterial agent.

Synthesis of 1,2,4‐Oxadiazole‐sulfonamide Conjugates and Their Synergistic Effect with Ampicillin as Antimicrobial Agents

“…It was performed according to the standard protocol of NCCLS [19] . The test compounds (8 c , 8 g , and 8 i ) were studied for their antibacterial activity against E. coli , K. pneumonieae , P. aeruginosa , B. subtilis , E. faecalis and S. aureus using the conventional broth dilution method [11,20] . The MIC values were calculated and compared with ciprofloxacin (CIP) and ampicillin (AMP) as the reference antibiotics.…”

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors

“…The 96-well plates were kept in an incubator shaker at 100 rpm for 24 h. The MIC was determined as the lowest concentration that prevented observable cell growth. All experiments were conducted with three biological triplicates [ 45 , 46 ].…”

“…Discs with doses equivalent to ½ MIC, MIC, and 2MIC were placed on a solid nutrient agar medium and incubated overnight at 37 °C. After incubation, the zone of inhibition (mm) was recorded and analyzed as explained in Ali et al [ 46 ].…”

“…A time–kill curve study was performed against bacterial strains (E. coli , E. faecalis, K. pneumonia and P. aeruginosa ) to determine whether compound PS9 is bactericidal or bacteriostatic. MIC, 2MIC and 4MIC concentrations were employed for the time–kill assay as explained by Ali et al [ 46 ]. Untreated bacterial cells were used as a control.…”

Acrylonitrile adducts: design, synthesis and biological evaluation as antimicrobial, haemolytic and thrombolytic agent

“…In recent years, the majority of infectious diseases have been linked to bacteria, as a result of widespread antibiotic resistance among bacteria strains. According to the 2016 United Nations (UN) declaration on antimicrobial resistance 1,2 , global plans and initiatives to address antimicrobial resistance are advancing. If current trends continue, bacterial infections with multidrug-resistant traits will be listed among the top three global public health risks, causing up to 10 million fatalities worldwide by 2050 [3][4][5] .…”