Synthesis, Characterization, in silico and in vivo Evaluation of Amino Acid Derived Schiff Bases of Quinoline-Benzimidazole Hybrids as Anti-epileptic Agents

Abstract:

Aim/Background: Novel quinoline compounds containing benzimidazole have been synthesized in a number of different ways and screened for anti-epileptic potential through in vivo and in silico studies. Materials and Methods: The novel quinoline-benzimidazole hybrids were synthesized by using substituted carbaldehyde (1,2) and substituted benzimidazole (derived from amino acids) (3a-f). The synthesized derivatives were characterized by IR, 13C-NMR, 1 H-NMR, and Mass spectroscopy and anti-convulsant activity was analyzed by in silico studies on the swiss albino mice using the ScPTZ model. Conclusion and Results: Compounds (1H-Benzoimidazol-2-yl)- substituted-(2-p-tolyloxy-quinolin-3-ylmethylene)-amine (4a-f) and (Benzoimidazol-2-yl)- substituted-(2-ethoxy-quinolin-3-ylmethylene)-amine (5a-f) were synthesized. The synthesized derivatives were characterized (IR, 13C-NMR, 1 H-NMR, and mass spectrometry) and screened for their anticonvulsant potentiality by subcutaneous pentylenetetrazol method using carbamazepine. Additionally, the anti-epileptic potential of the produced compounds is confirmed by in silico study results that were obtained. The study also proved that the synthesized derivatives used aminobutyric acid (GABAA) receptors. At a dose level of 30 mg/kg body weight, 4a, 4b, and 4d were found to be more effective than the other synthesized derivatives.

Keywords: Seizure, Anti-epileptic, Quinoline, Benzimidazole, Subcutaneous pentylenetetrazol.