title: 8-(Furan-2-yl)-3-phenethylthiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione as novel, selective and potent adenosine A(2A) receptor antagonist.
abstract: Antagonism of the human A2A receptor has been implicated to alleviate the symptoms associated with Parkinson's disease. The present finding reveals the potential of PTTP (8-(furan-2-yl)-3-phenethylthiazolo[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione) as novel and potent A2AR antagonist. In radioligand binding assay, PTTP showed significantly high binding affinity (Ki 6.3 nM) and selectivity with A2AR (A1R/A2AR=4603) which was comparable to the results of docking analysis (Ki=1.6 nM, ΔG=-14.52 Kcal/mol). PTTP antagonized (0.46 pmol/ml) the effect of NECA-induced increase in cAMP concentration (0.65 pmol/ml) better than SCH58261 (0.55 pmol/ml) in HEK293T cells. Haloperidol and NECA-induced mice pre-treated with PTTP at 10mg/kg showed attenuation in catalepsy and akinesia without significant neurotoxicity in rotarod test at 20mg/kg. Essentially, novel compound demonstrated remarkable potential as A2AR antagonist in the therapy of PD.
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Kumari
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
authors.forename: Amresh
authors.initials: A
authors.lastname: Prakash
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Mongre
authors.affiliation: Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India. Electronic address: pmlsci@yahoo.com.
authors.forename: Pratibha Mehta
authors.initials: PM
authors.lastname: Luthra
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D045442:Rotarod Performance Test; D014230:Triazoles / Q000494:pharmacology*
chemical_list: C000590216:8-(furan-2-yl)-3-phenethylthiazolo(1,2,4)triazolo(1,5-c)pyrimidine-2(3H)-thione; D058917:Adenosine A2 Receptor Antagonists; D006575:Heterocyclic Compounds, 3-Ring; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D000242:Cyclic AMP; C030986:pyrimidine
keywords: Adenosine A(2A) receptors (A(2A)R); Catalepsy; Motor activity; Mouse models of Parkinson; PTTP; cAMP