Condensation of 4-benzoyl-1,2-phenylenediamine with sodium pyruvate in acetic acid furnished two products which were identified as 6-benzoyl and 7-benzoyl-3-methyl-2(1H)quinoxalinones (1a,b). Fusion of 1a with aromatic aldehydes furnished the styryl derivatives 2a-c. Alkylation of 1a,b with dimethyl sulphate or ethyl chloroacetate produced the N-alkyl derivatives 3a,b and 4a,b. Hydrazinolysis of the ester derivative 4a with hydrazine hydrate afforded the hydrazide derivative 5 which underwent condensation with aldehydes to give the corresponding hydrazone derivatives 6a,b. In addition, chlorination of 1a with thionyl chloride afforded the 2-chloro derivative 7 which was subjected to reaction with sodium azide and n-butylamine to yield the corresponding tetrazolo (8) and n-butylamino (9) derivatives, respectively. The structures of the compounds prepared were confirmed by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity.

A series of thiazol-4-one/thiophene-bearing pyrazole derivatives as pharmacologically attractive cores were initially synthesized using a hybridization approach. All structures were confirmed using spectra analysis techniques (IR, ¹H NMR, and ¹³C NMR). In vitro antimicrobial activities, including the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and time-kill assay, were evaluated for the most active derivatives 4a, 5a, 7b, 10, and 13. These derivatives were significantly active against the tested pathogens, with compound 7b as the most active derivative (MIC values range from 0.22 to 0.25 μg/mL). In the MBC and MFC, the active target pyrazole derivatives showed -cidal activities toward the pathogenic isolates. Further, the inhibition of biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis was also carried out. Additionally, these derivatives displayed significant antibiofilm potential with a superior % reduction in the biofilm formation compared with Ciprofloxacin. The target derivatives behaved synergistically with Ciprofloxacin and Ketoconazole, reducing their MICs. Hemolytic results revealed that these derivatives were nontoxic with a significantly low hemolytic activity (%lysis range from 3.23 to 15.22%) compared with Triton X-100 and showed noncytotoxicity activity with IC₅₀ values > 60 μM. In addition, these derivatives proved to be active DNA gyrase and DHFR inhibitors with IC₅₀ ranging between 12.27–31.64 and 0.52–2.67 μM, respectively. Furthermore, compound 7b showed bactericidal activity at different concentrations in the time-kill assay. Moreover, a gamma radiation dose of 10.0 kGy was efficient for sterilizing compound 7b and enhancing its antimicrobial activity. Finally, molecular docking simulation of the most promising derivatives exhibited good binding energy with different interactions.