title: Design, synthesis, anticonvulsant evaluation and docking study of 2-[(6-substituted benzo[d]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothioureas.
abstract: In this paper, we report the synthesis of 2-[(6-substituted benzo[d]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothiourea derivatives (4a-y) carrying active pharmacophores essential for anticonvulsant activity. The anticonvulsant activity was evaluated in vivo by maximal electroshock (MES) test and subcutaneous pentylenetetrazole (scPTZ) test in mice. Most of the compounds showed promising anticonvulsant activity. The most active compounds 4b and 4q were found active in both MES and scPTZ models, without signs of neurotoxicity. Compound 4b showed the moderate change in SGOT and alkaline phosphatase level as compared to control. Compounds 4b and 4w were also found to elevate GABA levels in the olfactory lobe, mid brain, medulla oblongata and cerebellum regions of rat brain. In molecular docking study, the title compounds exhibited good binding properties with epilepsy molecular targets such as GABA-A. Structure-activity relationships are also elaborated along with the analysis of lipophilicity. The results suggested that compound 4b is likely to have varied mechanisms of action including voltage-gated ion channel inhibition and modulating GABAergic action.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: nadeems_03@yahoo.co.in.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Siddiqui
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India; Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box no. 114, Jazan University, Jazan, Saudi Arabia.
authors.forename: Md Shamsher
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Meeta
authors.initials: M
authors.lastname: Sahu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Mohd Javed
authors.initials: MJ
authors.lastname: Naim
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: M Shahar
authors.initials: MS
authors.lastname: Yar
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Ozair
authors.initials: O
authors.lastname: Alam
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D052160:Benzothiazoles; D011963:Receptors, GABA-A; D013890:Thiourea
keywords: Anticonvulsant activity; Benzothiazoles; GABA-A; Molecular docking; Structure-activity relationship; Toxicity