Synthesis, antimicrobial activity, and in silico studies of fluoroquinolones bearing 1,3,4-oxadiazolyl-triazole derivatives

Compounds containing fluoroquinolone (FQ) moiety occupy privileged chemical space for discovering novel bioactive substances. In continuation of our research work, a new series of FQs linked to triazolyl-thiadiazine hybrids (3a-f) and triazolyl-oxadiazoles (5a-f) were developed as a new antimicrobial agent targeting DNA gyrase of Staphylococcus aureus. All the novel compounds have been characterized with IR, H-1 NMR, C-13 NMR, mass spectral analysis and elemental analysis. All the synthesized derivatives were investigated for their antibacterial effect against various bacterial and fungal strains. Against Gram-positive bacteria S. aureus, compounds 3e, 5a, and 5d showed the highest antibacterial activity with minimum inhibitory concentrations (MIC) values 5.0 & PLUSMN; 0.04, 8.6 & PLUSMN; 0.03, and 6.1 & PLUSMN; 0.02 & mu;g/mL, respectively. FQ derivatives 3a, 5c had the most potent antibacterial activity against Klebsiella pneumonia bacteria with MICs 6.4 & PLUSMN; 0.01, 4.1 & PLUSMN; 0.01 & mu;g/mL and compounds 3e, 5d are active against Gram-negative bacteria Bacillus cereus with MICs 8.3 & PLUSMN; 0.02, 10.0 & PLUSMN; 0.02 & mu;g/mL, respectively. Interestingly, the molecules 3e were slightly more selective towards antifungal activity against Fusarium oxysporum (MIC 4.2 & PLUSMN; 0.01 & mu;g/mL), compared to fluconazole (MIC 3.5 & PLUSMN; 0.01 & mu;g/mL). In addition, a fascinating molecular modeling investigation showed that our FQs 3, 5 demonstrated good binding inhibition of S. aureus complex in DNS gyrase (2XCT) towards advancing an efficient medication against antibacterial disease. The prepared ligand 3c forms three hydrogen bonds with amino acid residues LysB:1043 (N23 horizontal ellipsis NZ), ArgB:1092 (O20 horizontal ellipsis NH), GlyB:1082 (O horizontal ellipsis N) with bond lengths 3.13, 2.15, 2.76 A & DEG;, respectively.