Aim: With the rapid emergence of antibiotic resistance, efforts are being made to obtain new selective antimicrobial agents. Hybridization between quinazolinone and benzenesulfonamide can provide new antimicrobial candidates. Also, the use of nanoparticles can help boost drug efficacy and lower side effects.
Materials And Methods: Novel quinazolinone-benzenesulfonamide derivatives were synthesized and screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, MRSA and yeast. The most potent compound was conjugated with copper oxide nanoparticles 16-CuONPs by gamma irradiation (4.5 KGy). Characterization was performed using UV-Visible, TEM examination, XRD patterns and DLS. Moreover, compound was used to synthesize two nanoformulations: 16-CNPs by loading in chitosan nanoparticles and the nanocomposites 16-CuONPs-CNPs. Characterization of these nanoformulations was performed using TEM and zeta potential. Besides, the inhibitory profile against DNA gyrase was assayed. Cytotoxic evaluation of , 16-CNPs and 16-CuONPs-CNPs on normal VERO cell line was carried out to determine its relative safety. Molecular docking of was performed inside the active site of DNA gyrase.
Results: Compound was the most active in this series against all the tested strains and showed inhibition zones and MICs in the ranges of 25-36 mm and 0.31-5.0 µg/mL, respectively. The antimicrobial screening of the synthesized nanoformulations revealed that 16-CuONPs-CNPs displayed the most potent activity. The MBCs of and the nanoformulations were measured and proved their bactericidal mode of action. The inhibitory profile against DNA gyrase showed IC ranging from 10.57 to 27.32 µM. Cytotoxic evaluation of , 16-CNPs and 16-CuONPs-CNPs against normal VERO cell lines proved its relative safety (IC= 927, 543 and 637 µg/mL, respectively). Molecular docking of inside the active site of DNA gyrase showed that it binds in the same manner as that of the co-crystallized ligand, ciprofloxacin.
Conclusion: Compound could be considered as a new antimicrobial lead candidate with enhanced activity upon nanoformulation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211327 | PMC |
| http://dx.doi.org/10.2147/IJN.S241433 | DOI Listing |
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