title: Development of Novel Triazolo-Thiadiazoles from Heterogeneous "Green" Catalysis as Protein Tyrosine Phosphatase 1B Inhibitors.
abstract: Condensed-bicyclic triazolo-thiadiazoles were synthesized via an efficient "green" catalyst strategy and identified as effective inhibitors of PTP1B in vitro. The lead compound, 6-(2-benzylphenyl)-3-phenyl-[1,2,4]triazolo[3][1,3,4]thiadiazole (BPTT) was most effective against human hepatoma cells, inhibits cell invasion, and decreases neovasculature in HUVEC and also tumor volume in EAT mouse models. This report describes an experimentally unidentified class of condensed-bicyclic triazolo-thiadiazoles targeting PTP1B and its analogs could be the therapeutic drug-seeds.
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560001, India.
authors.forename: C P
authors.initials: CP
authors.lastname: Baburajeev
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
authors.forename: Chakrabhavi
authors.initials: C
authors.lastname: Dhananjaya Mohan
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
authors.forename: Hanumappa
authors.initials: H
authors.lastname: Ananda
authors.affiliation: Frontier Research Center for Post-genome Science and Technology, Hokkaido University, Sapporo 0600808, Japan.
authors.forename: Shobith
authors.initials: S
authors.lastname: Rangappa
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Fuchs
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
authors.forename: Swamy
authors.initials: S
authors.lastname: Jagadish
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore-117597, Singapore.
authors.forename: Kodappully
authors.initials: K
authors.lastname: Sivaraman Siveen
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saudi University, Riyadh -11451, Kingdom of Saudi Arabia.
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Chinnathambi
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saudi University, Riyadh -11451, Kingdom of Saudi Arabia.
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Ali Alharbi
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saudi University, Riyadh -11451, Kingdom of Saudi Arabia.
authors.forename: M E
authors.initials: ME
authors.lastname: Zayed
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore-117597, Singapore.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore-117597, Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore-117597, Singapore.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
authors.forename: Kesturu S
authors.initials: KS
authors.lastname: Girish
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.affiliation: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560001, India.
authors.lastname: Basappa
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D019938:Cyclin D1 / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D009361:Neoplasm Invasiveness / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013329:Structure-Activity Relationship; D000077022:Survivin; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000609854:6-(2-benzylphenyl)-3-phenyl-(1,2,4)triazolo(3)(1,3,4)thiadiazole; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001572:Benzofurans; D002867:Chromones; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D013830:Thiadiazoles; D014230:Triazoles; D019938:Cyclin D1; C477157:sanggenone C; D011065:Poly(ADP-ribose) Polymerases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D053148:Caspase 3