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

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 screenedin vitrofor their antibacterial activities against the two bacterial strainsMicrococcus luteusandPseudomonas aeruginosa. According to the results obtained, compounds4 a,4 d, and4 eshowed the lowest MIC value that was comparable to that for tetracycline with strong inhibition (MIC=62.5 mg/mL) againstM. luteusand also compound4 bexhibited the lowest MIC (62.5 mg/mL) againstP. aeruginos. Moreover, the results of the antibacterial activity of the synthesized compounds were investigated using molecular docking calculations. Insilicostudies showed that the screened molecules could occupy both pterin andp-aminobenzoic acid binding pockets of the dihydropteroate synthase enzyme. Thus, the active compounds could act using the inhibition of bacterial dihydropteroate synthase.