Synthesis and characterization of some new Schiff base derivatives of gabapentin, and assessment of their antibacterial, antioxidant and anticonvulsant activities

Purpose: To synthesize and characterize some new gabapentin Schiff base derivatives, and to assess their antibacterial, antioxidant and antiepileptic activities. Methods: Four Schiff base derivatives of gabapentin, termed G1, G2, G3 and G4, were synthesized by condensation with benzoin, vanillin, acetophenone, and benzophenone, respectively. Their chemical identities were established by FTIR, 1H NMR and 13C NMR techniques. The new compounds were screened for antibacterial activity using agar well method, antioxidant activity by DPPH assay, and anticonvulsant activity against pentylenetetrazole (PTZ) induced seizures in mice. Results: All the compounds showed antibacterial activity against the test strains to variable degrees, while the parent drug did not exhibit antibacterial activity. The zones of inhibition of compound G2 against Micrococcus luteus (36.2 ± 1.0 mm) and Serratia marcescens (28.2 ± 1.0 mm), and of compound G4 against Stenotrophomonas maltophilia (36.8 ± 1.0 mm) were larger compared to the standard drug, doxycycline, exhibiting zones of inhibition 28.2 ± 1.3, 28.2 ± 0.9 and 20.0 ± 0.9 mm, respectively. In addition, compounds G1 and G2 possessed significantly greater (p < 0.05) radical scavenging activity (82.3 ± 1.8 and 92.3 ± 2.2 %, respectively) than the precursor drug, gabapentin (63.2± 2.6 %). The seizure scores for compounds G1 (0.7 ± 0.06) and G2 (0.9 ± 0.07) were comparable (p > 0.05) with gabapentin (0.8 ± 0.06), while compounds G3 and G4 were less active (p < 0.05) than gabapentin. Conclusion: Compounds G1 and G2 exhibit good antibacterial and antioxidant activities while retaining the anticonvulsant activity of the parent drug, gabapentin, thus making them suitable candidates for further development for the treatment of neurodegenerative pathologies associated with bacterial infections.