Development of Novel Triazolo-Thiadiazoles from Heterogeneous "Green" Catalysis as Protein Tyrosine Phosphatase 1B Inhibitors

C P Baburajeev; Chakrabhavi Dhananjaya Mohan; Hanumappa Ananda; Shobith Rangappa; Julian E Fuchs; Swamy Jagadish; Kodappully Sivaraman Siveen; Arunachalam Chinnathambi; Sulaiman Ali Alharbi; M E Zayed; Jingwen Zhang; Feng Li; Gautam Sethi; Kesturu S Girish; Andreas Bender; Basappa; Kanchugarakoppal S Rangappa

doi:10.1038/srep14195

Development of Novel Triazolo-Thiadiazoles from Heterogeneous "Green" Catalysis as Protein Tyrosine Phosphatase 1B Inhibitors

Sci Rep. 2015 Sep 21:5:14195. doi: 10.1038/srep14195.

Authors

C P Baburajeev¹, Chakrabhavi Dhananjaya Mohan², Hanumappa Ananda², Shobith Rangappa³, Julian E Fuchs⁴, Swamy Jagadish², Kodappully Sivaraman Siveen⁵, Arunachalam Chinnathambi⁶, Sulaiman Ali Alharbi⁶, M E Zayed⁶, Jingwen Zhang⁵, Feng Li⁵, Gautam Sethi⁵, Kesturu S Girish⁷, Andreas Bender⁴, Basappa¹, Kanchugarakoppal S Rangappa²

Affiliations

¹ Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560001, India.
² Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-570006, India.
³ Frontier Research Center for Post-genome Science and Technology, Hokkaido University, Sapporo 0600808, Japan.
⁴ Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.
⁵ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore-117597, Singapore.
⁶ Department of Botany and Microbiology, College of Science, King Saudi University, Riyadh -11451, Kingdom of Saudi Arabia.
⁷ Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore-570006, India.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Benzofurans / pharmacology
Carcinoma, Ehrlich Tumor / drug therapy
Carcinoma, Hepatocellular / drug therapy*
Caspase 3 / biosynthesis
Cell Line, Tumor
Cell Movement / drug effects
Chromones / pharmacology
Cyclin D1 / biosynthesis
Disease Models, Animal
Dose-Response Relationship, Drug
Female
G1 Phase Cell Cycle Checkpoints / drug effects
Hep G2 Cells
Human Umbilical Vein Endothelial Cells
Humans
Inhibitor of Apoptosis Proteins / biosynthesis
Liver Neoplasms / drug therapy*
Mice
Models, Molecular
Neoplasm Invasiveness / pathology
Neovascularization, Pathologic / drug therapy
Poly(ADP-ribose) Polymerases / biosynthesis
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Rats
Rats, Sprague-Dawley
STAT3 Transcription Factor / metabolism
Structure-Activity Relationship
Survivin
Thiadiazoles / chemical synthesis
Thiadiazoles / pharmacology*
Triazoles / chemical synthesis
Triazoles / pharmacology*

Substances

6-(2-benzylphenyl)-3-phenyl-(1,2,4)triazolo(3)(1,3,4)thiadiazole
Antineoplastic Agents
BIRC5 protein, human
Benzofurans
Chromones
Inhibitor of Apoptosis Proteins
Proto-Oncogene Proteins c-bcl-2
STAT3 Transcription Factor
STAT3 protein, human
Survivin
Thiadiazoles
Triazoles
Cyclin D1
sanggenone C
Poly(ADP-ribose) Polymerases
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Caspase 3