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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.

Alzheimer’s disease (AD) represents the principal cause of dementia among the elderly. Great efforts have been established to understand the physiopathology of AD. Changes in neurotransmitter systems in patients with AD, including cholinergic, GABAergic, serotoninergic, noradrenergic, and histaminergic changes have been reported. Interestingly, changes in the histaminergic system have been related to cognitive impairment in AD patients. The principal pathological changes in the brains of AD patients, related to the histaminergic system, are neurofibrillary degeneration of the tuberomammillary nucleus, the main source of histamine in the brain, low histamine levels, and altered signaling of its receptors. The increase of histamine levels can be achieved by inhibiting its degrading enzyme, histamine N-methyltransferase (HNMT), a cytoplasmatic enzyme located in astrocytes. Thus, increasing histamine levels could be employed in AD patients as co-therapy due to their effects on cognitive functions, neuroplasticity, neuronal survival, neurogenesis, and the degradation of amyloid beta (Aβ) peptides. In this sense, the evaluation of the impact of HNMT inhibitors on animal models of AD would be interesting, consequently highlighting its relevance.

Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown. Therefore, in this study, in vitro and computational studies were performed to determine the mechanism of action of perezone. Firstly, changes in K562 cell viability, as well as changes in the redox status of the cell in response to treatment with several concentrations of perezone were analyzed. The type of cell death induced, and the modification of the cell cycle were determined. In addition, MD simulations and docking studies were performed to investigate the interaction of perezone with seven regulators of the apoptotic process. Finally, the ability of perezone to inhibit PARP-1 was evaluated by in vitro studies. K562 cells treated with perezone exhibited decreased viability and more oxidized status, being this effect concentration-dependent. In addition, the increase of G0/G1 phase of cell cycle and apoptosis were observed. According to the performed computational studies conducted, perezone showed the highest affinity to PARP-1 enzyme being this complex the most stable due to the presence of a small and deep cavity in the active site, which allows perezone to fit deeply by forming hydrogen bonds and hydrophobic interactions, which drive this interaction. The activity of perezone as PARP-1 inhibitor was corroborated with an IC50 = 181.5 μM. The pro-apoptotic action of perezone may be related to PARP-1 inhibition and changes in the redox state of the cell. The obtained results allowed to understand the biological effect of perezone and, consequently, these could be employed to develop novel PARP-1 inhibitors.

Oxidative stress is related to the pathogenesis and progress of several human diseases. NADPH oxidase (NOX), and mainly the NOX2 isoform, produces superoxide anions (O2•- ). To date, it is known that NOX2 can be inhibited by preventing the assembly of its subunits, p47phox and p22phox. In this work, we analyzed the binding to NOX2 of the apocynin dimer, diapocynin (C1), a known NOX2 inhibitor, and of 18 designed compounds (C2-C19) which have chemical relationships to C1, by in silico methods employing a p47phox structure from the Protein Data Bank (PDB code: 1WLP). C1 and six of the designed compounds were recognized in the region where p22phox binds to p47phox and makes π-π interactions principally with W193, W263, and Y279, which form an aromatic-rich region. C8 was chosen as the best compound according to the in silico studies and was synthesized and evaluated in vitro. C8 was able to prevent the production of reactive oxygen species (ROS) similar to C1. In conclusion, targeting the aromatic region of p47phox through π-interactions is important for inhibiting NOX activity.

It is know that compounds with phenol and thiol moieties have antioxidant activity. Therefore, the aim of this study was to synthetized three compounds containing phenol and thiol groups ((cysteine...