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Review
. 2022 Apr 19;27(9):2615.
doi: 10.3390/molecules27092615.

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective

Bhaskar C Das  1   2   3 , Nitesh K Nandwana  1   2 , Sasmita Das  1 , Varsha Nandwana  1 , Mohammed Adil Shareef  1 , Yogarupa Das  4 , Mariko Saito  4 , Louis M Weiss  5 , Frankis Almaguel  6 , Narayan S Hosmane  7 , Todd Evans  3
Affiliations
Review

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective

Bhaskar C Das et al. Molecules. .

Abstract

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure-activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer's agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

Keywords: ALS; aminoboronic acids; bezoxaboroles; boron-containing drugs; boron-containing retinoids; brain cancer; lipogenic inhibitors; proteasome inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples and highlights of boron chemistry in drug discovery.
Figure 2
Figure 2
(A) o-carboranes. (B) Borophene layers. Top and side view of a B7 cluster as a constituting unit. (C) Fragment of a B36 borophene molecule. (D) Proposed primary and secondary interactions at the boron center.
Scheme 1
Scheme 1
Boron-containing stilbene derivatives as potential drug candidates.
Scheme 2
Scheme 2
Boron drug for treatment amyotrophic lateral sclerosis.
Scheme 3
Scheme 3
Boronic-acid-containing proteasome inhibitors.
Scheme 4
Scheme 4
Boranophosphate nucleosides as an inhibitors of HIV reverse transcriptase (RT).
Scheme 5
Scheme 5
(A) Borate complexes. (B) Baran’s protocol for the synthesis of HNE inhibitors.
Scheme 6
Scheme 6
Boromycin.
Scheme 7
Scheme 7
Potent boronic-acid-derived inhibitor of HCV.
Scheme 8
Scheme 8
Peptide-boronic acid inhibitors of flaviviral proteases.
Scheme 9
Scheme 9
Fluoro-substituted 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles as antimalarial agents.
Scheme 10
Scheme 10
6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles as antimalarial agents.
Scheme 11
Scheme 11
AN4161 as an anti-inflammatory agent.
Scheme 12
Scheme 12
Ectoparasiticide activity of an isoxazoline-containing boraxozole.
Scheme 13
Scheme 13
Antitrypanosomal activity of 6-pyrrolobenzoxaborole scaffold.
Scheme 14
Scheme 14
AN6414, a novel boron-containing PDE4 inhibitor.
Scheme 15
Scheme 15
Synthesis oftavaborole: antifungal drug.
Scheme 16
Scheme 16
AN2690 for the potential treatment of onychomycosis.
Scheme 17
Scheme 17
A potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.
Scheme 18
Scheme 18
Benzoxaborole derivatives as antibacterial agents.
Scheme 19
Scheme 19
Benzoxaboroles as a new class of β-lactamase inhibitors.
Scheme 20
Scheme 20
Cyclic boronic acid as a β-lactamase inhibitor (RPX7009).
Scheme 21
Scheme 21
Novel P2X7 receptor antagonist with antidepressant activity.
Scheme 22
Scheme 22
Synthesis of thymine-linked lipophilic 1,12-dicarba-closo-dodecaborane and 1,2-dicarba-closo-dodecaborane derivatives.
Scheme 23
Scheme 23
Asborin: the carbaborane analogue of aspirin.
Scheme 24
Scheme 24
m-Carborane-containing estrogen receptor partial agonists as SERM candidates.
Scheme 25
Scheme 25
Prodrugs of 3-carboranyl thymidine analogues as antitumor agents.
Scheme 26
Scheme 26
p-Carborane-based potent non-secosteroidal vitamin D analogues.
Scheme 27
Scheme 27
Boron-containing nonclassical antifolates.
Scheme 28
Scheme 28
Carborane-derived local anesthetics.
Scheme 29
Scheme 29
Antileukemic activity of novel adenosine derivatives bearing a boron cluster.
Scheme 30
Scheme 30
Androgen antagonists based on carborane as a hydrophobic core.
Scheme 31
Scheme 31
m-Carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor.
Scheme 32
Scheme 32
Bifunctional mitochondriatargeted as ananticancer agent.
Scheme 33
Scheme 33
Difluoroboron-derivatized curcumins for in vivo detection of amyloid-β-deposits.
Scheme 34
Scheme 34
2-Aminoethoxydiphenyl borate for the treatment of allergic rhinitis.
Scheme 35
Scheme 35
2(S)-Amino-6-boronohexanoic acid (ABH) used for the treatment of anthrax.
Scheme 36
Scheme 36
Nitric oxide synthase activation and inhibition by metallocarboraneclusters.
Scheme 37
Scheme 37
2-Acylated 2,3,1-benzodiazaborines as an anti-bacterial agent.
Scheme 38
Scheme 38
Amino boron compounds as an antit-uberculosis agents.
Scheme 39
Scheme 39
Oxazaborones as NLRP3 inflammasome inhibitors.
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References

    1. Baker S.J., Ding C.Z., Akama T., Zhang Y.-K., Hernandez V., Xia Y. Therapeutic potential of boron-containing compounds. Future Med. Chem. 2009;1:1275–1288. doi: 10.4155/fmc.09.71. - DOI - PubMed
    1. Maslah H., Skarbek C., Pethe S., Labruère R. Anticancer boron-containing prodrugs responsive to oxidative stress from the tumor microenvironment. Eur. J. Med. Chem. 2020;207:112670. doi: 10.1016/j.ejmech.2020.112670. - DOI - PubMed
    1. Song S., Gao P., Sun L., Kang D., Kongsted J., Poongavanam V., Zhan P., Liu X. Recent developments in the medicinal chemistry of single boron atom-containing compounds. Acta Pharm. Sin. B. 2021;11:3035–3059. doi: 10.1016/j.apsb.2021.01.010. - DOI - PMC - PubMed
    1. Das B.C., Thapa P., Karki R., Schinke C., Das S., Kambhampati S., Banerjee S.K., Van Veldhuizen P., Verma A., Weiss L.M. Boron chemicals in diagnosis and therapeutics. Future Med. Chem. 2013;5:653–676. doi: 10.4155/fmc.13.38. - DOI - PMC - PubMed
    1. Das B.C., Ojha D.P., Das S., Evans T. Boron-Based Compounds: Potential and Emerging Applications in Medicine. John Wiley & Sons; New York, NY, USA: 2018. Boron Compounds in Molecular Imaging; pp. 205–231.

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