Synthesis and Preclinical Validation of Novel Indole Derivatives as a GPR17 Agonist for Glioblastoma Treatment.

ABSTRACT: The discovery of a potential ligand-targeting G protein-coupled receptor 17 (GPR17) is important for developing chemotherapeutic agents against glioblastoma multiforme (GBM). We used the integration of ligand- and structure-based cheminformatics and experimental approaches for identifying the potential GPR17 ligand for GBM treatment. Here, we identified a novel indoline-derived phenolic Mannich base as an activator of GPR17 using molecular docking of over 6000 indoline derivatives. One of the top 10 hit molecules, CHBC, with a glide score of -8.390 was synthesized through a multicomponent Petasis borono-Mannich reaction. The CHBC-GPR17 interaction leads to a rapid decrease of cAMP and Ca²⁺. CHBC exhibits the cytotoxicity effect on GBM cells in a dose-depende

SUBMITTER: Nguyen P 

PROVIDER: S-EPMC8389915 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature