Aryl-isoquinoline as a potential scaffold for novel antitumor agents against glioblastoma cells (original) (raw)

Letters in Drug Design & Discovery

Abstract

Background: Glioblastoma is one of the most aggressive types of tumors, which occurs in the central nervous system, and has a high fatality rate. Among the cellular changes observed in glioblastoma is the overexpression of certain anti-apoptotic proteins, such as Bcl-xL. Recently, the alkaloid sanguinarine (SAN) was identified as a potent inhibitor of this class of proteins. Objective: In this work, the antitumor activity of ten aryl-isoquinolines that were synthesized based on molecular simplification of SAN was investigated. Methods: The SAN derivatives were prepared by Suzuki reaction and bimolecular nucleophilic substitution. The compounds were tested against glioblastoma (U87MG) and melanoma (A375) tumor lines in the MTT and SRB assay. The cell death mechanism was evaluated by flow cytometry. The molecular modeling study was used to evaluate the interactions between the prepared compounds and the Bcl-xL protein. Results: Analogues presented IC50 values against glioblastoma lowe...

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