Turning Fear of Boron Toxicity into Boron-containing Drug Design

Abstract

Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat

“…Although the mechanisms involved in the observed behavior and neuronal changes induced by borolatonin administration in this cognitive deficit by hormonal deprivation must be clearly established, the observed changes are interesting in this first approach. Moreover, borolatonin is an attractive compound, considering that BCCs have shown increased affinity on the receptors of their analogous boron-free compounds [ 31 ], which could be in line with the findings in the current work, where the effects were similar to the number of borolatonin molecules, which was lower than that of the analogous melatonin (albeit they were 10 mg/kg each, due to the molecular weight of borolatonin being higher for borolatonin than for melatonin), but also, due to the increased half-time and prolonged action proposed for BCCs [ 13 ]. Diverse limitations exist, confirming the role of direct interaction on melatonin receptors, even if theoretical evaluation strongly suggest the ability of borolatonin to act on them.…”

“…On the other hand, boron-containing compounds (BCCs) possess expanding actions as therapeutic agents [ 11 , 12 , 13 ]. Today, boric acid, bortezomib, tavaborole, crisaborole, and vaborbactam are allowed to use in humans, but many other BCCs are showing attractive effects as potential treatments in human diseases, including neurological diseases.…”

“…Today, boric acid, bortezomib, tavaborole, crisaborole, and vaborbactam are allowed to use in humans, but many other BCCs are showing attractive effects as potential treatments in human diseases, including neurological diseases. The mechanisms for potential therapeutic action of BCCs in the nervous system involve neuronal action through enzyme inhibition [ 14 ], acting as ligands of membrane receptors [ 13 , 15 ], regulating immune response [ 16 ], glial activities [ 17 ], and levels and the action of brain-derived growth factors [ 18 , 19 ]. Thus, action of BCCs on neuronal disease models are increasing [ 20 , 21 ].…”

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders

“…Several nano-scale materials are used in nanomedicine: organic, inorganic, carbon-based, polymeric, liposomes, extracellular vesicles, and metals [ 2 , 3 , 4 ]. Boron-containing compounds (BCCs) have a wide range of medicinal effects [ 5 , 6 , 7 ]. Currently, only a few BCCs, such as vaborbactam, tavaborole, crisaborole, and bortezomib, are permitted for use in people.…”

Exposure to boron trioxide nanoparticles and ions cause oxidative stress, DNA damage, and phenotypic alterations in Drosophila melanogaster as an in vivo model

“…For that reason, ecotoxicity of such materials should be thoroughly evaluated for the health of organisms inhabiting those areas, with the assessment of risks and hazards (Chifiriuc et al, 2016; Demir, 2020, 2021a; el Kholy et al, 2021; Pappus & Mishra, 2018; Wang et al, 2022). Among the metal and metalloid‐type NPs, boron NPs are commonly used for fuel engine support material (Ojha & Karmakar, 2018) and in medical applications (Soriano‐Ursúa et al, 2019; Zhu & Hosmane, 2018). Boron trioxide (B 2 O 3 )‐based substances are considerably utilized in electronic device technologies, solar and energy technologies, and acoustic‐optic apparatus fields (Albert & Hillebrecht, 2009; Hermann et al, 2013; Lipp et al, 1989).…”