TY - JOUR
T1 - Synthesis, characterization of novel isoindolinyl- and bis-isoindolinylphenylboronic anhydrides. Antiproliferative activity on glioblastoma cells and microglial cells assays of boron and isoindolines compounds
AU - Mancilla Percino, Teresa
AU - Guzmán Ramírez, José Eduardo
AU - Mera Jiménez, Elvia
AU - Trejo Muñoz, Cynthia Raquel
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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; 1H, 13C, 11B NMR, IR and HRMS. 1H and 11B 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.
AB - 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; 1H, 13C, 11B NMR, IR and HRMS. 1H and 11B 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.
KW - Boronanhydrides
KW - Glioblastoma
KW - Isoindolines
KW - Isoindolinylboranes
KW - Microglia cells
KW - N-B bond coordination
UR - http://www.scopus.com/inward/record.url?scp=85064381872&partnerID=8YFLogxK
U2 - 10.1016/j.jorganchem.2019.04.011
DO - 10.1016/j.jorganchem.2019.04.011
M3 - Artículo
AN - SCOPUS:85064381872
SN - 0022-328X
VL - 891
SP - 35
EP - 43
JO - Journal of Organometallic Chemistry
JF - Journal of Organometallic Chemistry
ER -