Schiff Bases of Benzothiazol-2-ylamine and Thiazolo[5,4-b] pyridin-2-ylamine as Anticonvulsants: Synthesis, Characterization and Toxicity Profiling.
BACKGROUND
Schiff bases have a broad spectrum of biological activities like antiinflammatory, analgesic, antimicrobial, anticonvulsant, antitubercular, anticancer, antioxidant, anthelmintic and so forth. Thus, after a thorough perusal of literature, it was decided to conjugate benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine with aromatic and heteroaromatic aldehydes to get a series of Schiff bases.


OBJECTIVE
Synthesis, characterization, in-silico toxicity profiling and anticonvulsant activity of the Schiff bases of Benzothiazol-2-ylamine and Thiazolo [5, 4-b] pyridin-2-ylamine.


METHODS
Aniline/4-aminopyridine was converted to the corresponding thiourea derivatives, which were cyclized to obtain benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine. Finally, these were condensed with various aromatic and heteroaromatic aldehydes to obtain Schiff bases of benzothiazol-2-ylamine and thiazolo [5, 4-b] pyridin-2-ylamine. The synthesized compounds were characterized and screened for their anticonvulsant activity using maximal electroshock (MES) test and isoniazid (INH) induced convulsions test. In-silico toxicity profiling of all the synthesized compounds was done through "Lazar" and "Osiris" properties explorer.


RESULTS
Majority of the compounds were more potent against MES induced convulsions than INH induced convulsions. Schiff bases of benzothiazol-2-ylamine were more effective than thiazolo [5, 4-b] pyridin-2-ylamine against MES induced convulsions. The compound benzothiazol-2-yl-(1H-indol-2-ylmethylene)-amine (VI) was the most potent member of the series against both types of convulsions.


CONCLUSIONS
Compound VI exhibited the most significant activity profile in both the models. The compounds did not exhibit any carcinogenicity or acute toxicity in the in-silico studies. Thus, it may be concluded that the Schiff bases of benzothiazol-2-ylamine exhibit the potential to be promising and non-toxic anticonvulsant agents.
Rashmi
R
Shukla
Ajeet P
AP
Singh
Pankaj K
PK
Sonar
Mudita
M
Mishra
Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Sector-2, Dr. Akhilesh Das Nagar, Faizabad Road, Lucknow, 227105, U.P., India.
Shailendra K
SK
Saraf
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000633:toxicity*; D008297:Male; D051379:Mice; D012545:Schiff Bases / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000633:toxicity*; D023382:Toxicity Tests, Acute / Q000379:methods
D000927:Anticonvulsants; D052160:Benzothiazoles; D012545:Schiff Bases; D013844:Thiazoles