Synthesis, characterization of novel isoindolinyl- and bis-isoindolinylphenylboronic anhydrides. Antiproliferative activity on glioblastoma cells and microglial cells assays of boron and isoindolines compounds

摘要

Boron compounds importance have been raising due to the development of its synthesis and remarkable biological activities, so in this manner the study here presented is focused on the synthesis of novel isoindolinylphenylboronic anhydrides (2a, 2c and 2e) and bis-isoindolinylphenylboronic anhydrides (2b and 2d), as well as a comparative study of the antiproliferative activity of these and their precursors (a-e), 1(a-e) over glioblastoma cells U373 and the cytotoxic activity over normal microglial cells. All compounds were characterized by spectroscopic methods; H-1, C-13, B-11 NMR, IR and HRMS. H-1 and B-11 NMR data at variable temperature of 2b and 2d showed equilibrium between species that contain a tetrahedral and a trigonal boron atom due to an intramolecular N -> B coordination and decoordination bond. The study of frontier molecular orbitals of B-derivatives showed that 2b' and 2d' are harder molecules than 2a, 2c and 2e, therefore can react with a second isoindoline to obtain 2b and 2d. Whereas, HOMO site of potassium derived 1bK and 1dK are over NCHCO2K moiety, consequently, to react with 2b' and 2d' to obtain 2b and 2d. These results clarify the obtainment of 2a-2d independently of the equimolecular ratio of reagents. On another hand, the biological assay showed that compound 2d possessed the most pronounced effect over U373 cells with no effect over normal microglial cells, providing a new set of boron compounds with important antitumoral activity. (C) 2019 Elsevier B.V. All rights reserved.