Title:Design, Synthesis, and Screening of Hybrid Benzothiazolyl-Oxadiazoles as Anticonvulsant Agents
VOLUME: 15 ISSUE: 4
Author(s):Sheikh Murtuja, Mohammad Shaquiquzzaman and Mohammad Amir*
Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi -110062, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi -110062, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi -110062
Keywords:Benzothiazole, oxadiazole, anticonvulsant, minimal motor impairment, CNS depressant, synergistic effect.
Abstract:Background: Epilepsy affects approximately 50 million people globally. It is generally
characterized by periodic seizures of unpredictable nature, though a variety of anticonvulsant drugs
are available but the major drawback is undesirable side effects. Here an effort is being made to
utilise the beneficial effect of benzothiazoles and oxadiazoles as potent anticonvulsants and there is
an anticipation of synergistic effect from the hybrid molecule.
Methods: Here a series of new hybrid molecules containing oxadiazole and benzothiazole pharmacophore
were synthesised using appropriate synthetic route and characterised by IR, 1H NMR, 13C
NMR, mass and elemental analysis. The synthesised compounds were examined for their maximal
electroshock seizure (MES) and subcutaneous pentylene tetrazole (Sc PTZ) induced seizure and
neurotoxicity screens. Those found potent were also evaluated for their CNS depressant effect.
Results: Among the compounds tested 4m N-(6-fluro-1,3-benzothiazol-2-yl)-2-{[5-(pyridin-4-yl)-
1,3,4-oxadiazol-2-yl]sulfanyl}acetamide and 4n N-(6-Chloro-1,3-benzothiazol-2-yl)-2-{[5-(pyridin-
4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl} acetamide showed protection from seizures in both the animal
models at dose level of 30 mg/kg after 0.5 hr and at 100 mg/kg after 4 hr period indicating that the
compound is potent and long acting. These compounds also exhibited lesser CNS depression and
neurotoxicity.
Conclusion: Among the synthesized compounds 4m and 4n possessed significant anticonvulsant
activity without any neurotoxicity and CNS depressant effects. Thus the hybrid benzothiazolyl
acetamide derivatives containing oxadizole scaffold provided a new opportunity for possible modification
and future exploitation to get the safer and effective anticvulsant agents.
