A novel of quinoxaline derivatives tagged with pyrrolidinyl scaffold as a new class of antimicrobial agents: Design, synthesis, antimicrobial activity, and molecular docking simulation

Abstract

Globally, infectious diseases are becoming harder to treat due to antibiotic resistance, which has reached high levels. Additionally, developing new therapeutic options to combat the growing antimicrobial resistance in clinical settings is necessary. The new 3-(pyrrolidin-1-yl)quinoxaline derivatives 4–10 conjugated with a different substituent at C2 through ether or amine linkage were synthesized via nucleophilic substitution reaction. The structure of quinoxaline derivatives was confirmed by IR, 1H NMR, and 13C NMR spectra. The antimicrobial activity of quinoxaline derivatives 4–10 varied from good to potency against the tested strains. The quinoxaline derivatives 4, 6, and 7 exhibited excellent activity, especially against B. pumilis and E. cloacae, with MIC values of (7.8, 15.6, and 3.91 µg/mL) and (15.6, 7.8, and 15.6 µg/mL) compared with Ciprofloxacin (7.8 and 15.6 µg/mL). Further, hybrid quinoxaline with different methanimine moieties at C2 showed moderate to good antimicrobial activity, except methanimine 9 and 10 that had MIC values equipotent to Ciprofloxacin 15.6 and 31.25 µg/mL against E. coli and S. faecalis, respectively. On the other hand, all these derivatives revealed good to weak antifungal activity with MIC (31.25–500 µg/mL) and MFC (62.5–1000 µg/mL) against A. niger and C. albicans. Moreover, most of the quinoxaline derivatives exhibited bactericidal and fungicidal activity, except for quinoxaline derivatives 9 and 10, which displayed bacteriostatic against E. coli. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of DNA gyrase pocket indicating that these compounds could inhibit the enzyme and cause promising antimicrobial effects.