title: Design, synthesis and anti-Parkinsonian evaluation of 3-alkyl/aryl-8-(furan-2-yl)thiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thiones against neuroleptic-induced catalepsy and oxidative stress in mice.
abstract: A series of 3-alkyl/aryl-8-(furan-2-yl)thiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thiones (3a-3f) were synthesised in good yield and evaluated for their anti-Parkinsonian and neuroprotective potential. The structures of the synthesised compounds were confirmed on the basis of their spectral data and elemental analysis. All of the compounds were found to be active in haloperidol-induced catalepsy and oxidative stress in mice. The most active compound carried a propyl group at the 3-position of the thiazolotriazolopyrimidine nucleus while substitution with a phenyl ring produced the least active compound among the series. A computational study was carried out for the prediction of pharmacokinetic properties and none of the compounds violated Lipinski's rule of five, making them potentially promising agents for the treatment of Parkinson's disease.
authors.affiliation: Laboratory of Medicinal Chemistry, Faculty of Pharmacy, University of Seventh October, Misurata, Libya. azamfaizul@yahoo.co.in
authors.forename: Faizul
authors.initials: F
authors.lastname: Azam
authors.forename: Bashir A
authors.initials: BA
authors.lastname: El-gnidi
authors.forename: Ismail A
authors.initials: IA
authors.lastname: Alkskas
authors.forename: Musa A
authors.initials: MA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D005663:Furans / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013871:Thiones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D015415:Biomarkers; D005663:Furans; D018696:Neuroprotective Agents; D011743:Pyrimidines; D013871:Thiones; D014230:Triazoles; D010088:Oxidoreductases; D005978:Glutathione