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(1H)-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 Neisseriagonorrhoeae, equipotent potency of ampicillin in inhibiting the growth of Streptococcuspyogenes, equipotent potency of gentamycin in inhibiting the growth of Proteusvulgaris and Shigella flexneri, equipotent potency of amphotericin B in inhibiting the growth of Aspergillus clavatus, Geotrichumcandidum 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.