Synthesis and molecular modeling of antimicrobial active fluoroquinolone–pyrazine conjugates with amino acid linkers

[Display omitted] •Designed and synthesized a set of hybrid conjugates using amino acid as linker.•Synthesized conjugates shows comparable antibacterial activity.•Computational (2D-QSAR and 3D pharmacophore) supports the biological data.•Developed QSAR model could be useful tool for new drug development. Novel fluoroquinolone–pyrazine conjugates 7a–h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6μM and 149.3μM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67μM and 92.9μM, respectively).