Discovery of a novel sunitinib derivatives bearing boron cluster moiety as potent anti-glioblastoma agent

GARCIA MF; CERECETTO H.; SIRE COUTO M.; GAVISH M; GABAY M; DAVILA B; TEIXEDOR F; ALAMÓN C.; TRIAS E.; KOVACS M.; DAGROSA MA; NIEVAS S; VIÑAS C

Campinas, Galoá

Simposio; 10th Brazilian Symposium on Medicinal Chemistry; 2022

BrazMedChem 2022

Glioblastoma is the most frequent and the most malignant type of brain tumor among infiltrative gliomas, a group of primary tumors arising from the central nervous system. There are no effective treatments yet. However, tyrosine kinase receptor (TKR) inhibitors and boron neutron capture therapy (BNCT), together, have been proposed as future therapeutic strategies1. In this sense in our ongoing project of developing new anti-glioblastoma drugs, we identified a sunitinib-carborane hybrid agent, 1, with both in vitro selective cytotoxicity and excellent BNCT-behavior2. Consequently, we studied the ability of compound 1 to inhibit TKRs, its promotion of cellular death processes, and its effects on the cell cycle. Moreover, we analyzed some relevant drug-like properties of 1, i.e., mutagenicity, ability to cross the blood–brain barrier, mechanism of cell death, among others. The in vivo activity in immunosuppressed mice bearing U87 MG human glioblastoma evidenced excellent anti-tumor behavior3.