title: Molecular docking study, green synthesis and pharmacological evaluation of 1,3,4-thiadiazole derivatives as potential antiepileptic agents.
abstract: Epilepsy is one of the commonly occurring chronic neurological disorders which involves abnormal electrical impulses in the brain. It is characterized by the sudden loss of consciousness, followed by abnormal shaking of the body. Though there are various types of antiepileptic drugs available clinically, the treatment of epilepsy still remains inadequate because of their toxicity and idiosyncratic side effects. Thus, there is unmet medical need to develop safe drugs for the treatment of epilepsy with lower side effects and improved bioavailability profiles. Considering the structural similarity between phenytoin/lamotrigine, a series of 1,3,4-thiadiazole was designed based on molecular docking study into the active site of the voltage-gated sodium channels. Antiepileptic activity of the synthesized compounds was evaluated in rats by maximal electroshock induced seizures (MES) model at different doses. Among the tested compounds, some exhibited significant anticonvulsant activity as compared to phenytoin in a dose-dependent manner. The neurotoxicity study was carried out using the rotarod test and the results of which suggests that the target compounds are safe and could be further developed as potential lead for antiepileptic drugs.
authors.forename: Biswa Mohan
authors.initials: BM
authors.lastname: Sahoo
authors.forename: S C
authors.initials: SC
authors.lastname: Dinda
authors.forename: B V V
authors.initials: BV
authors.lastname: Ravi Kumar
authors.forename: J R
authors.initials: JR
authors.lastname: Panda
authors.affiliation: SPER, Berhampur University, Bhanja Bihar-760 007, Odisha, India. pathik26@yahoo.com.
authors.forename: Pathik S
authors.initials: PS
authors.lastname: Brahmkshatriya
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D004195:Disease Models, Animal; D004597:Electroshock; D005260:Female; D055772:Green Chemistry Technology; D008297:Male; D008872:Microwaves; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D018675:Toxicity Tests
chemical_list: D000927:Anticonvulsants; D015222:Sodium Channels; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole