Design, synthesis and biological evaluation of quinoxaline N-propionic and O-propionic hydrazide derivatives as antibacterial and antifungal agents

Novel series of quinaxoline derivatives incorporating N -propionic and O -propionic hydrazide moieties were synthesized. Alkylation of 3-methylquinoxalin-2(1 H )-one with ethyl 2-bromopropanoate afforded a mixture of O -alkylated and N -alkylated 3-methylquinoxaline. Hydrazide derivatives were afforded by reaction of O -alkylated and N -alkylated 3-methylquinoxaline with hydrazine hydrate. Condensation of hydrazide derivatives with different aromatic aldehydes and formylpyrazoles afforded the corresponding hydrazone derivatives. The synthesized quinaxoline derivatives were evaluated for their expected antimicrobial activity; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Hydrazone derivative which contain 3- p -tolyl-pyrazolyl moiety showed fourfold potency of amphotericin B in inhibiting the growth of Aspergillus fumigatus , twofold potency of gentamycin in inhibiting the growth of Neisseria gonorrhoeae , equipotent potency of ampicillin in inhibiting the growth of Streptococcus pyogenes , equipotent potency of gentamycin in inhibiting the growth of Proteus vulgaris and Shigella flexneri , equipotent potency of amphotericin B in inhibiting the growth of Aspergillus clavatus , Geotrichum candidum and Penicillium marneffei . Thus, these studies suggested that quinaxoline derivatives bearing a pyrazole moiety are interesting scaffolds for the development of novel antibacterial and antifungal agents.