Design,Synthesis,Antibacterial Evaluation and Molecular Docking Study of New 3-Aminoquinoxaline-2-alkynyl Carboxylate Esters

摘要

Antibacterial chemotherapy is the clinical application of the antibiotic drug to treat infectious disease.A new series of 3-aminoquinoxaline-2-alkynyl carboxylate esters have been synthesized through the multi-component copper-free Sonogashira coupling reaction.Aromatic and aliphatic carboxylic acids were successfully reacted with 3-bromoprop-1-yne and different amine substituted 3-chloroquinoxalines in the presence of a Pd-catalyst to produce the new 3-(3-(aminoquinoxalin-2-yl)prop-2-yn-1-yl carboxylates.All the newly synthesized compounds were screened in vitro for their antibacterial activities against the two bacterial strains Micrococcus luteus and Pseudomonas aeruginosa.According to the results obtained,compounds 4a,4d,and 4e showed the lowest MIC value that was comparable to that for tetracycline with strong inhibition(MIC=62.5 mg/mL)against M.luteus and also compound 4b exhibited the lowest MIC(62.5 mg/mL)against P.aeruginos.Moreover,the results of the antibacterial activity of the synthesized compounds were investigated using molecular docking calculations.In silico studies showed that the screened molecules could occupy both pterin and p-aminobenzoic acid binding pockets of the dihydropteroate synthase enzyme.Thus,the active compounds could act using the inhibition of bacterial dihydropteroate synthase.