title: Design, synthesis and biological evaluation of 5-benzylidene-2-iminothiazolidin-4-ones as selective GSK-3β inhibitors.
abstract: In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2-85 nM). Further, in vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Minhajul
authors.initials: M
authors.lastname: Arfeen
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Bhagat
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Shivcharan
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Roy
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India.
authors.forename: Asit K
authors.initials: AK
authors.lastname: Chakraborti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062, Punjab, India. Electronic address: pvbharatam@niper.ac.in.
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001667:Binding, Competitive; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D053778:Thiazolidines; D000255:Adenosine Triphosphate; D000071679:Glycogen Synthase Kinase 3 beta
keywords: CDK-2; GSK-3; Molecular docking; Molecular dynamics; SBDD