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Bioorganic & Medicinal Chemistry Jun 2022The incorporation of the "magic" boron atom has been established as an important new strategy in the field of medicinal chemistry as boron compounds have been shown to... (Review)
Review
The incorporation of the "magic" boron atom has been established as an important new strategy in the field of medicinal chemistry as boron compounds have been shown to form various bonds with their biological targets. Currently, a number of boron-based drugs (e.g. bortezomib, crisaborole, and tavaborole) have been FDA approved and are in the clinic, and several other boron-containing compounds are in clinical trials. Boron-based heterocycles have an incredible potential in the ongoing quest for new therapeutic agents owing to their plethora of biological activities and useful pharmacokinetic profiles. The present perspective is intended to review the pharmacological applications of boron-based heterocycles that have been published. We have classified these compounds into groups exhibiting shared pharmacological activities and discussed their corresponding biological targets focusing mainly on the most potent therapeutic compounds.
Topics: Boron; Bortezomib; Chemistry, Pharmaceutical
PubMed: 35453036
DOI: 10.1016/j.bmc.2022.116748 -
Pharmacology & Therapeutics Nov 2023Boron has become a crucial weapon in anticancer research due to its significant intervention in cell proliferation. Being an excellent bio-isosteric replacement of... (Review)
Review
Boron has become a crucial weapon in anticancer research due to its significant intervention in cell proliferation. Being an excellent bio-isosteric replacement of carbon, it has modulated the anticancer efficacy of various molecules in the development pipeline. It has elicited promising results through interactions with various therapeutic targets such as HIF-1α, steroid sulfatase, arginase, proteasome, etc. Since boron liberates alpha particles, it has a wide-scale application in Boron Neutron Capture therapy (BNCT), a radiotherapy that demonstrates selectivity towards cancer cells due to high boron uptake capacity. Significant advances in the medicinal chemistry of boronated compounds, such as boronated sugars, natural/unnatural amino acids, boronated DNA binders, etc., have been reported over the past few years as BNCT agents. In addition, boronated nanoparticles have assisted the field of bio-nano medicines by their usage in radiotherapy. This review exclusively focuses on the medicinal chemistry aspects, radiotherapeutic, and chemotherapeutic aspects of boron in cancer therapeutics. Emphasis is also given on the mechanism of action along with advantages over conventional therapies.
Topics: Humans; Boron; Boron Compounds; Neoplasms; Antineoplastic Agents; Boron Neutron Capture Therapy
PubMed: 37858628
DOI: 10.1016/j.pharmthera.2023.108548 -
Medicinal Research Reviews Sep 2023Boron neutron capture therapy (BNCT) is one of the most promising treatments among neutron capture therapies due to its long-term clinical application and... (Review)
Review
Boron neutron capture therapy (BNCT) is one of the most promising treatments among neutron capture therapies due to its long-term clinical application and unequivocally obtained success during clinical trials. Boron drug and neutron play an equivalent crucial role in BNCT. Nevertheless, current clinically used l-boronophenylalanine (BPA) and sodium borocaptate (BSH) suffer from large uptake dose and low blood to tumor selectivity, and that initiated overwhelm screening of next generation of BNCT agents. Various boron agents, such as small molecules and macro/nano-vehicles, have been explored with better success. In this featured article, different types of agents are rationally analyzed and compared, and the feasible targets are shared to present a perspective view for the future of BNCT in cancer treatment. This review aims at summarizing the current knowledge of a variety of boron compounds, reported recently, for the application of BCNT.
Topics: Humans; Boron Neutron Capture Therapy; Boron; Neoplasms; Boron Compounds
PubMed: 37102375
DOI: 10.1002/med.21964 -
Bioorganic Chemistry Feb 2024Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and... (Review)
Review
Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications.
Topics: Humans; Carbonic Anhydrase Inhibitors; Boron; Carbonic Anhydrases; Protein Isoforms; Neoplasms; Boron Compounds; Structure-Activity Relationship
PubMed: 38000350
DOI: 10.1016/j.bioorg.2023.106976 -
Chemical Record (New York, N.Y.) Jul 2023Catalytic, chemoselective, and asymmetric α-functionalizations of carboxylic acids promise up-grading simple feedstock materials to value-added functional molecules, as... (Review)
Review
Catalytic, chemoselective, and asymmetric α-functionalizations of carboxylic acids promise up-grading simple feedstock materials to value-added functional molecules, as well as late-stage structural diversifications of multifunctional molecules, such as drugs and their leads. In this personal account, we describe boron-catalyzed α-functionalizations of carboxylic acids developed in our group (five reaction types). The reversible boron carboxylate formation is key to the acidification of the α-protons and enolization using mild organic bases, allowing for chemoselective and asymmetric bond formations of carboxylic acids. The ligand effects on reactivity and stereoselectivity, substrate scopes, and mechanistic insights are summarized.
Topics: Carboxylic Acids; Boron; Catalysis
PubMed: 36639245
DOI: 10.1002/tcr.202200273 -
International Journal of Molecular... Feb 2020Boron is an essential plant micronutrient taken up via the roots mostly in the form of boric acid. Its important role in plant metabolism involves the stabilization of... (Review)
Review
Boron is an essential plant micronutrient taken up via the roots mostly in the form of boric acid. Its important role in plant metabolism involves the stabilization of molecules with -diol groups. The element is involved in the cell wall and membrane structure and functioning; therefore, it participates in numerous ion, metabolite, and hormone transport reactions. Boron has an extremely narrow range between deficiency and toxicity, and inadequate boron supply exhibits a detrimental effect on the yield of agricultural plants. The deficiency problem can be solved by fertilization, whereas soil boron toxicity can be ameliorated using various procedures; however, these approaches are costly and time-consuming, and they often show temporary effects. Plant species, as well as the genotypes within the species, dramatically differ in terms of boron requirements; thus, the available soil boron which is deficient for one crop may exhibit toxic effects on another. The widely documented intraspecies genetic variability regarding boron utilization efficiency and toxicity tolerance, together with the knowledge of the physiology and genetics of boron, should result in the development of efficient and tolerant varieties that may represent a long-term sustainable solution for the problem of inadequate or excess boron supply.
Topics: Boron; Cell Wall; Plant Roots; Plants; Soil
PubMed: 32093172
DOI: 10.3390/ijms21041424 -
Advances in Nutrition (Bethesda, Md.) Mar 2020
Topics: Animals; Boron; Diet; Humans; Nutritional Physiological Phenomena; Plants, Edible
PubMed: 31639188
DOI: 10.1093/advances/nmz110 -
Cells May 2023BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological... (Review)
Review
BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT delivery. Given this, developing novel boronated compounds with high selectivity, ease of delivery, and large boron payloads remains an area of active investigation. Furthermore, there is growing interest in exploring the immunogenic potential of BNCT. In this review, we discuss the basic radiobiological and physical aspects of BNCT, traditional and next-generation boron compounds, as well as translational studies exploring the clinical applicability of BNCT. Additionally, we delve into the immunomodulatory potential of BNCT in the era of novel boron agents and examine innovative avenues for exploiting the immunogenicity of BNCT to improve outcomes in difficult-to-treat malignancies.
Topics: Humans; Boron; Boron Neutron Capture Therapy; Neoplasms; Boron Compounds; Radiobiology
PubMed: 37408232
DOI: 10.3390/cells12101398 -
International Journal of Molecular... Jun 2020Although very recently, David H [...].
Although very recently, David H [...].
Topics: Agriculture; Boron; Fertilizers; Gene Expression Regulation, Plant; Micronutrients; Plant Proteins; Plant Roots; Plants
PubMed: 32526846
DOI: 10.3390/ijms21114107 -
Chemico-biological Interactions May 2023Boron is shown in the present review to induce hormetic dose responses in a broad range of biological models, organ systems and endpoints. Of particular importance is... (Review)
Review
Boron is shown in the present review to induce hormetic dose responses in a broad range of biological models, organ systems and endpoints. Of particular importance is that numerous hormetic findings have been reported with whole animal studies, with extensive dose response evaluations with the optimal dosing being similar across multiple organ systems. These findings appear to be underappreciated and suggest that boron may have clinically significant systemic effects beyond that of its putative and more subtle essentiality functions. The re-exploration of boron's bioactivity as seen through hormetic mechanisms may also underscore the value of this approach to the assessment of micronutrient effects in human health and disease.
Topics: Animals; Humans; Hormesis; Boron; Models, Biological; Trace Elements
PubMed: 36878460
DOI: 10.1016/j.cbi.2023.110432