Boron-containing compounds on neurons: Actions and potential applications for treating neurodegenerative diseases

Barrón-González, Mónica; Montes-Aparicio, A.V.; Cuevas-Galindo, M. Emilio; Orozco-Suárez, S.; Barrientos, Rafael; Alatorre, Alberto; Querejeta, E.; Trujillo‐Ferrara, José G.; Farfán‐García, Eunice D.; Soriano‐Ursúa, Marvin A.

doi:10.1016/j.jinorgbio.2022.112027

Cited by 11 publications

(14 citation statements)

References 123 publications

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“…However, the essentiality of boron in supporting animal life is substantiated by the detrimental effects of boron deficiency, 39 such as impeding embryo development, 40−43 pulmonary fibrosis, 44 osteoporosis, 45−49 cognitive function, 50,51 calcium and magnesium concentration, 52−55 and steroid hormone concentration. 56,57 As boric acid and borates enter animal/human cells, they interact with and often disrupt the kinetics and dynamics of other biomolecules containing cisdiols, such as flavin adenine dinucleotide, nicotinamide adenine dinucleotide (NAD), ribonucleic acids, ribonuclease, and S-adenosyl methionine (SAM).…”

Section: Introduction: Boron-containing Compounds In Naturementioning

confidence: 99%

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

Grams,

Santos,

Scorei

et al. 2024

Chem. Rev.

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Boron-containing compounds (BCC) have emerged as important pharmacophores. To date, five BCC drugs (including boronic acids and boroles) have been approved by the FDA for the treatment of cancer, infections, and atopic dermatitis, while some natural BCC are included in dietary supplements. Boron's Lewis acidity facilitates a mechanism of action via formation of reversible covalent bonds within the active site of target proteins. Boron has also been employed in the development of fluorophores, such as BODIPY for imaging, and in carboranes that are potential neutron capture therapy agents as well as novel agents in diagnostics and therapy. The utility of natural and synthetic BCC has become multifaceted, and the breadth of their applications continues to expand. This review covers the many uses and targets of boron in medicinal chemistry.

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Section: Introduction: Boron-containing Compounds In Naturementioning

confidence: 99%

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

Grams,

Santos,

Scorei

et al. 2024

Chem. Rev.

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“…[17] Heterocyclic molecules containing boron can interact with ionotropic channels in the neuron. [14] For example, while (+)-(S)-Trujillone activates the NMDA receptor, 2-APB affects Ca + 2 currents as an IP3 receptor antagonist. [18] Although many NMDA channel blockers have been developed to date, moderate NMDA channel blockers are clinically preferred because they do not show serious side effects like high affinity channel blockers.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, diphenhydramine which is an antihistamine and structurally similar to 2-APB, acts predominantly through histamine receptors and on sodium channels. [14] Disruption of the balance of neuronal excitation and inhibition causes epileptic seizures. Excitatory neurotransmission is a fundamental process for normal brain function, and it is mediated by glutamate, which is the most abundant neurotransmitter in the CNS.…”

Section: Introductionmentioning

confidence: 99%

“…Phenytoin, a drug used in the treatment of epilepsy, is active on cationic sodium channels, while its organoboron counterpart 2‐aminoethyldiphenyl borinate (2‐APB) is active on calcium channels. Moreover, diphenhydramine which is an antihistamine and structurally similar to 2‐APB, acts predominantly through histamine receptors and on sodium channels [14] …”

Section: Introductionmentioning

confidence: 99%

“…Influx of calcium ions triggers a cascade of intracellular signaling events, which are thought to be important for synaptic plasticity and learning [17] . Heterocyclic molecules containing boron can interact with ionotropic channels in the neuron [14] . For example, while (+)‐(S)‐Trujillone activates the NMDA receptor, 2‐APB affects Ca +2 currents as an IP3 receptor antagonist [18]…”

Section: Introductionmentioning

confidence: 99%

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Title: A Boron‐Chelating Piperazine‐Tethered Schiff Base Can Modulate Excitability in Brain Slices in a Specific Frequency Range

Basoglu,

Degirmencioglu,

Ozturk

et al. 2023

ChemistrySelect

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The ability of boron‐containing compounds to make various bonds with biological targets draws attention in their use as new therapeutic agents. In this study, the effect of a newly synthesized molecule with the short name fmpemboron, “Difluoro [2‐[([2‐[4‐(2,3,4‐trimethoxybenzyl)piperazin‐1‐yl]ethyl] imino‐κN)methyl]phenolato‐κO]boron (5)”on the excitability of neurons in the brain was investigated for the first time. First of all, fmpemboron was synthesized and characterized. Secondly, virtual scanning of the molecule was performed using ADME and molecular docking methods. Then, epileptiform activities were induced in mouse brain slices using Mg‐free or 4AP methods, and the effect of fmpemboron (5) at different concentrations was examined. The absorbance peak wavelength of fmpemboron (5) is between 330–340 nm and the fluorescence emission peak is 435 nm. According to ADME and molecular docking results, fmpemboron (5) can cross the blood‐brain barrier (BBB) and has affinity for the NMDA receptor. It also significantly reduces the power of oscillations between 8–12 Hz and 13–29 Hz in epileptiform activities generated by the Mg‐free method. Administration of 10 μM fmpemboron (5) had a modulatory effect on epileptiform activities, indicating that fmpemboron (5) can affect various neurological functions through NMDA channels. However, in‐vivo dose‐dependent studies are required to further investigate the effects of this novel molecule.

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Borolatonin limits cognitive deficit and neuron loss while increasing proBDNF in ovariectomised rats

Barrón‐González,

Rivera‐Antonio,

Jarillo‐Luna

et al. 2024

Fundamemntal Clinical Pharma

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BackgroundBorolatonin is a potential therapeutic agent for some neuronal diseases such as Alzheimer's disease (AD). Its administration exerts ameliorative effects such as those induced by the equimolar administration of melatonin in behavioral tests on male rats and in neuronal immunohistochemistry assays.ObjectiveIn this study, motivated by sex differences in neurobiology and the incidence of AD, the ability of borolatonin to induce changes in female rats was assessed.MethodsEffects of borolatonin were measured by the evaluation of both behavioral and immunohistopathologic approaches; additionally, its ability to limit amyloid toxicity was determined in vitro.ResultsSurprisingly, behavioral changes were similar to those reported in male rats, but not those evaluated by immunoassays regarding neuronal survival; while pro‐brain‐derived neurotrophic factor (BDNF) immunoreactivity and the limitation of toxicity by amyloid in vitro were observed for the first time.ConclusionBorolatonin administration induced changes in female rats. Differences induced by the administration of borolatonin or melatonin could be related to the differences in the production of steroid hormones in sex dependence. Further studies are required to clarify the possible mechanism and origin of differences in disturbed memory caused by the gonadectomy procedure between male and female rats.

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Boron-containing compounds on neurons: Actions and potential applications for treating neurodegenerative diseases

Cited by 11 publications

References 123 publications

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

Title: A Boron‐Chelating Piperazine‐Tethered Schiff Base Can Modulate Excitability in Brain Slices in a Specific Frequency Range

Borolatonin limits cognitive deficit and neuron loss while increasing proBDNF in ovariectomised rats

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