Indole-like Trk receptor antagonists
Jaana Tammiku-Taul1, Rahel Park2, Kaur Jaanson2
1University of Tartu, Institute of Chemistry, Ravila 14A, Tartu, 50411, Estonia; Tallinn University of Technology, Department of Chemistry, Akadeemia 15, Tallinn, 12618, Estonia.
Abstract:
The virtual screening for new scaffolds for TrkA receptor antagonists resulted in potential low molecular weight drug candidates for the treatment of neuropathic pain and cancer. In particular, the compound (Z)-3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxindole and its derivatives were assessed for their inhibitory activity against Trk receptors. The IC50 values were computationally predicted in combination of molecular and fragment-based QSAR. Thereafter, based on the structure-activity relationships (SAR), a series of new compounds were designed and synthesized. Among the final selection of 13 compounds, (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-N-methyl-2-oxindole-5-sulfonamide showed the best TrkA inhibitory activity using both biochemical and cellular assays and (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-2-oxindole-5-sulfonamide was the most potent inhibitor of TrkB and TrkC.
More Related Videos
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Related Concept Videos
Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
Phenothiazines, such as prochlorperazine...
Drug-Receptor Interaction: Antagonist
Antagonists can be classified as competitive or noncompetitive based on their...
Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
