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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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