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

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.

Microbiota-Accessible Boron-Containing Compounds in Complex Regional Pain Syndrome.

The microbiota-gut-brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota-gut-brain axis, offering hope for improved management of this challenging condition.

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives.

Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary (through Q1 of 2023) of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.

Zinc-Boron Complex-Based Dietary Supplements for Longevity and Healthy Life.

The nutritional role of zinc (Zn) and boron (B) in the plant-animal-human food chain is highly topical worldwide research. Our data indicated that Zn-B complex (ZBC)-based dietary supplements can be used as stable non-toxic formulations, with high intestinal absorption rate, inducing alpha2-macroglobulin (A2M) expression for longevity and healthy life. ZBC is metabolized by hydrolysis, mainly at the absorption site (intestinal level), and most of it is excreted in the urine. Within seven hours from the administration in mice, almost the entire amount of orally absorbed ZBC is eliminated in a metabolized form. The highest amount of A2M protein in mouse liver was determined by immunoabsorbance assay in the chronic experiment (1000mg/kg of ZBC), followed by the subchronic experiment (at the same dose of ZBC), and by the acute experiment (5000mg/kg of ZBC).

Zinc-Boron-PLGA biocomposite material: preparation, structural characterization, and in vitro assessment.

Nowadays, the state-of-the-art discoveries in the field of delivery systems for therapeutic purposes have redefined the importance of biocompatible and biodegradable poly(lactic-co-glycolic acid (PLGA) nanocomposites. The study aimed to obtain a biocomposite material, with improved properties of its constituents [zinc-boron (Zn-B) complex and PLGA], by a simple, cost-effective method. The water∕oil∕water double emulsion technique allowed the adjustment of the synthesis parameters, to maximize the degree of Zn-B complex encapsulation. The morphological aspects of the samples were established by scanning electron microscopy (SEM). Particle size distribution was determined by dynamic light scattering (DLS). Morphology was typical for PLGA, spherical one. Depending on the synthesis conditions, the obtained particles have diameters between 10-450 nm. Zeta potential (ZP) showed that the particles have electronegative surface charge, offering a favorable perspective on aggregation, flocculation, and dispersion phenomena. It was observed, applying the design of experiments, that the particles size increased with increasing amounts of PLGA and polyvinyl alcohol (PVA), while ZP increased with higher PLGA and smaller PVA amounts in the formulation. The encapsulation efficiency was determined by ultra-high performance liquid chromatography∕mass spectrometry (UHPLC∕MS). The in vitro assessment was performed using Vero CCL-81 epithelial cell line and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Zn-B-PLGA biocomposite has promising characteristics and can be used for future biomedical applications.

New Insights into Boron Essentiality in Humans and Animals.

Boron (B) is considered a prebiotic chemical element with a role in both the origin and evolution of life, as well as an essential micronutrient for some bacteria, plants, fungi, and algae. B has beneficial effects on the biological functions of humans and animals, such as reproduction, growth, calcium metabolism, bone formation, energy metabolism, immunity, and brain function. Naturally organic B (NOB) species may become promising novel prebiotic candidates. NOB-containing compounds have been shown to be essential for the symbiosis between organisms from different kingdoms. New insights into the key role of NOB species in the symbiosis between human/animal hosts and their microbiota will influence the use of natural B-based colon-targeting nutraceuticals. The mechanism of action (MoA) of NOB species is related to the B signaling molecule (autoinducer-2-borate (AI-2B)) as well as the fortification of the colonic mucus gel layer with NOB species from B-rich prebiotic diets. Both the microbiota and the colonic mucus gel layer can become NOB targets. This paper reviews the evidence supporting the essentiality of the NOB species in the symbiosis between the microbiota and the human/animal hosts, with the stated aim of highlighting the MoA and targets of these species.

Boron-containing compounds in Dentistry: a narrative review.

Research on the use of boron (B) in the field of oral health has gained momentum in recent years, with various studies on the possibilities of using various B-containing compounds (BCCs). A multitude of applications have been discovered, from cariostatic activity to anti-inflammatory and antifungal activity, paving the way for other new research directions. B is a microelement that is commonly found in the human diet, and present throughout the body, with the highest concentration in the structure of bones, teeth, and gastrointestinal mucus gel layer. Multiple studies have demonstrated that B plays some important roles, especially in bone development and recently has been proposed to have an essential role in the healthy symbiosis. In addition, B has also attracted the interest of researchers, as various studies used BCCs in conventional or modern biomaterials. In this review, we have brought together the information we have found about B updates in the dental field and analyzing its future perspectives and potential for further studies.

Preclinical and histological study of boron-containing compounds hydrogels on experimental model of periodontal disease.

Periodontitis is a disease that affects a wide group of people, and there has been an increased interest in the research of finding useful materials that help reduce inflammation and the further loss of tissue. In this study, we have tested a boron-containing compound (BCC) Calcium Fructoborate (CaFB) and Boric Acid (BA) hydrogels on the gingival level on Wistar rats. First, we have induced the periodontal disease at the lower incisors, we have applied the hydrogels and after a week, we have euthanized the rats. Next, the oral soft tissue reaction was clinically and then histologically investigated. Our study has shown good clinical response of the oral tissue, and we have noticed lower levels of inflammation on the experimental groups treated with the BCCs hydrogels. Despite the generally good response of the biological structures to the presence of BA and CaFB on periodontal level, more scientifically proved information is needed to obtain the desired biological responses in all clinical situations.

Natural and semisynthetic candidate molecules for COVID-19 prophylaxis and treatment.

Coronaviruses (CoVs) represent a family of viruses that have numerous animal hosts, and they cause severe respiratory, as well as systemic and enteric infections, in humans. Currently, there are limited antiviral strategies for treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of specific antiviral medicines and SARS-CoV-2 vaccines continues to aggravate the situation. Natural product-based antiviral drugs have been used in the two previous CoV outbreaks: Middle East respiratory syndrome coronavirus (MERS-CoV) and the first SARS-CoV. This review emphasizes the role of natural and semisynthetic candidate molecules for coronavirus disease 2019 (COVID-19) prophylaxis and treatment. The experimental evidence suggests that nature could offer huge possibilities for treatment of the COVID-19 pandemic.

The Fructoborates: Part of a Family of Naturally Occurring Sugar-Borate Complexes-Biochemistry, Physiology, and Impact on Human Health: a Review.

Sugar-borates (SBs) are mono- or di-sugar-borate esters (SBEs) comprised of one or two monosaccharide molecules linked to a boron (B) atom. SBEs occur naturally in commonly consumed herbs, vegetables, fruits, seeds, and nuts and, other than greatly varying levels of B found in local drinking water, are the primary natural dietary sources of B-containing molecules in humans. To date, the most studied SBE is calcium fructoborate (CaFB). CaFB represents an important example of how organic B-containing molecules are significantly distinct from their inorganic counterparts. During these past two decades, CaFB has been researched for its physical and biochemical characteristics, safety, and clinical outcomes. Results of these researches are presented and discussed herein. CaFB has been characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), high-performance thin-layer chromatography (HPTLC), nuclear magnetic resonance (NMR), liquid chromatography-multistage accurate mass spectrometry (LC-MSn), X-ray diffraction (XRD), Raman spectroscopy, and inductively coupled plasma (ICP) in non-biological and biological specimens. Potential health benefits of CaFB have been clinically investigated in pilot and efficacy studies demonstrating (i) significant reductions in knee discomfort and improved flexibility within 7, 14, and 90 days and (ii) significant effect on blood levels of inflammatory, cardiovascular, and other biomarkers. These studies support the use of CaFB as a dietary supplement for the management of joint discomfort. CaFB is presented here in order to illustrate how physiological benefits are imparted by distinct organic boron-containing molecules rather than solely by the element B itself. Considering recent National Health and Nutrition Examination Survey (NHANES) data reporting increases in age-related joint pain and an increasing elderly demographic, SBEs offer potential for safe, natural, and effective management of joint discomfort and improved mobility in human and animal health applications. Several of these studies may also open new opportunities for use of SBEs for health benefits beyond joint health.

Effects of boron-containing compounds on cardiovascular disease risk factors - A review.

Boron is considered to be a biological trace element but there is substantial and growing support for it to be classified as an essential nutrient for animals and humans, depending on its speciation. Boron-containing compounds have been reported to play an important role in biological systems. Although the exact biochemical functions of boron-containing compounds have not yet been fully elucidated, previous studies suggest an active involvement of these molecules in the mediation of inflammation and oxidative stress. Chronic inflammation and oxidative stress are known to amplify the effects of the main cardiovascular risk factors: smoking, diet, obesity, arterial hypertension, dyslipidemia, type 2 diabetes (as modifiable risk factors), and hyperhomocysteinemia and age (as independent risk factors). However, the role of boron-containing compounds in cardiovascular systems and disease prevention has yet to be established. This paper is a review of boron-containing compounds' existence in nature and their possible functions in living organisms, with a special focus on certain cardiovascular risk factors that may be diminished by intake of these compounds, leading to a reduction of cardiovascular morbidity and/or mortality.

Simultaneous Quantitation of Boric Acid and Calcium Fructoborate in Dietary Supplements by HPTLC-Densitometry.

The paper describes a new, simple, selective and precise high-performance thin-layer chromatographic (HPTLC) method for the simultaneous identification and quantitative determination of boric acid (BA) and calcium fructoborate (CFB) in bulk and tablet/capsule dosage forms of dietary supplements. HPTLC silica gel G 60 F254 precoated glass plates were used as the stationary phase. The mobile phase consisted of 2-propanol-water 8:2 (v/v). The two boron-based compounds were adequately separated with the Rf values of 0.83 ± 0.01 (BA) and 0.59 ± 0.01 (CFB).

Calcium fructoborate: plant-based dietary boron as potential medicine for cancer therapy.

It was predicted that more B-containing molecules will be discovered that will prove useful in applications involving cell surface signaling, but insufficient progress was made in this general direction. The main objective of this review is to reveal other promising research directions for B-chemoprevention and chemotherapy using Calcium Fructoborate (CF). Targets include breast cancer, prostate cancer, lung cancer and cervical cancer. CF has been identified as Ca ( (C6H10O6)2B)2o4H2O and is a natural product from plants (can be produced by chemical synthesis as well), and is efficient in the prevention and treatments (as adjuvant) of osteoporosis and osteoarthritis. CF showed inhibitory effects on MDA-MB-231 breast cancer cells as well, and enters the cell (most likely) by a co-transport mechanism via a sugar transporter. Inside cells CF acts as an antioxidant and induces the overexpression of apoptosis-related proteins and eventually apoptosis.