Design, synthesis of new novel quinoxalin-2(1H)-one derivatives incorporating hydrazone, hydrazine, and pyrazole moieties as antimicrobial potential with in-silico ADME and molecular docking simulation

A series of 6-(morpholinosulfonyl)quinoxalin-2(1H)-one based hydrazone, hydrazine, and pyrazole moieties were designed, synthesized, and evaluated for their in vitro antimicrobial activity. All the synthesized quinoxaline derivatives were characterized by IR, NMR (H-1/C-13), and EI MS. The results displayed good to moderate antimicrobial potential against six bacterial, and two fungal standard strains. Among the tested derivatives, six quinoxalin-2(1H)-one derivatives 4a, 7, 8a, 11b, 13, and 16 exhibited a significant antibacterial activity with MIC values (0.97-62.5 mu g/mL), and MBC values (1.94-88.8 mu g/mL) compared with Tetracycline (MICs = 15.62-62.5 mu g/mL, and MBCs = 18.74-93.75 mu g/mL), and Amphotericin B (MICs = 12.49-88.8 mu g/mL, and MFC = 34.62-65.62 mu g/mL). In addition, according to CLSI standards, the most active quinoxalin-2(1H)-one derivatives demonstrated bactericidal and fungicidal behavior. Moreover, the most active quinoxaline derivatives showed a considerable antibacterial activity with bactericidal potential against multi-drug resistance bacteria (MDRB) strains with MIC values ranged between (1.95-15.62 mu g/mL), and MBC values (3.31-31.25 mu g/mL) near to standard Norfloxacin (MIC = 0.78-3.13 mg/mL, and MBC = 1.4-5.32 mu g/mL. Further, in vitro S. aureus DNA gyrase inhibition activity were evaluated for the promising derivatives and displayed potency with IC50 values (10.93 +/- 1.81-26.18 +/- 1.22 mu M) compared with Ciprofloxacin (26.31 +/- 1.64 mu M). Interestingly, these derivatives revealed as good immunomodulatory agents by a percentage ranging between 82.8 +/- 0.37 and 142.4 +/- 0.98 %. Finally, some in silico ADME, toxicity prediction, and molecular docking simulation were performed and showed a promising safety profile with good binding mode. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

A series of compounds based on 6-(morpholinosulfonyl)quinoxalin-2(1H)-one were designed, synthesized, and evaluated for their in vitro antimicrobial activity, showing good potential against multi-drug resistance bacteria. These compounds also exhibited immunomodulatory and DNA gyrase inhibition activities.