Search Results (27)

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating DNA repair, mutagenesis, and phenotypic adaptation. Targeting this pathway represents a promising strategy to limit bacterial adaptability without directly affecting viability. This study aimed to evaluate benzoxaborole-based compounds as potential inhibitors of the LexA regulatory pathway. Methods: A drug repurposing approach was employed to investigate the benzoxaborole scaffold and the clinically approved derivatives tavaborole and crisaborole. Biochemical assays were used to assess LexA autocleavage in a RecA-dependent co-protease system. Molecular docking analyses were performed to evaluate compound binding within the LexA catalytic site. Microbiological assays were conducted to examine the effects on antibiotic-induced filamentation and biofilm formation under different growth conditions. Results: Selected benzoxaboroles inhibited LexA autocleavage, with tavaborole showing the strongest inhibitory profile in the biochemical assay. Docking analyses supported these findings, indicating stable binding within the LexA catalytic site near the catalytic serine residue. At the cellular level, tavaborole and benzoxaborole significantly reduced levofloxacin-induced filamentation at sub-inhibitory concentrations. Both compounds also decreased biofilm formation under nutrient-limited conditions, while no significant effects were observed on preformed biofilms. Crisaborole showed limited cellular activity despite measurable biochemical effects. Conclusions: These findings identify benzoxaboroles as modulators of the LexA-dependent SOS response and support the potential repurposing of clinically approved compounds as adjuvants to limit bacterial adaptive responses associated with antimicrobial resistance. Full article

Benzoxaboroles have garnered significant interest for their therapeutic potential in various diseases. Among them, 7-propanamide benzoxaborole has served as a new and valuable chemotype for anti-cancer agents, although their definitive intracellular target(s) remains elusive. Herein, three-dimensional quantitative structure–activity relationship (3D-QSAR) was used to systematically investigate the structure–activity relationships (SAR) of a series of 7-propanamide benzoxaboroles. Comparative molecular field analysis (CoMFA, r² = 0.991, q² = 0.626) and comparative molecular similarity indices analysis (CoMSIA, r² = 0.964, q² = 0.605) revealed critical structural determinants of 7-propanamide benzoxaboroles for inhibition of the ovarian cancer cell (SKOV3) proliferation. Based on the guidance of the critical structural determinants, we designed a new benzoxaborole compound 42 with high predicted inhibition activity values. In vitro proliferation assessment showed that compound 42 exhibited superior inhibitory potency to lead compound 1 and comparable activity to compound 41. These findings indicated that the SAR of benzoxaborole compounds through 3D-QSAR can offer valuable theoretical insights for the structural optimization of new benzoxaboroles as anti-SKOV3 agents. Full article

Since the approval of Bortezomib (Velcade^®) by the U.S. Food and Drug Administration (FDA) in 2003, boron-containing drugs have successfully entered the global market, spanning therapeutic areas such as anticancer, antibacterial, and antifungal agents. Meanwhile, boron is an essential trace element for plant growth, and boronic acid has been widely used as plant resistance inducers and growth promoters. In 2024, the Fungicide Resistance Action Committee (FRAC) introduced benzoxaboroles as a new category of fungicides, which fully demonstrates the significant application potential of boron-containing compounds (BCCs) in the field of agricultural fungicides. Recently, studies on BCCs in agriculture have emerged continuously. Compared with the systematic reviews in the pharmaceutical field, those focusing on BCCs in agriculture remain absent. This review systematically collates BCCs with reported biological activities from the literature over the past 20 years, from the perspective of boron-containing building blocks. It mainly focuses on the potential of boronic acid derivatization and its activities in agrochemicals. Additionally, it covers the applications of boron-containing building blocks in pharmaceuticals, including their action mechanisms. Full article

Organoboron compounds, especially those containing boronic acid and benzoxaborole in their structure, have been gaining prominence in medicinal chemistry, following the FDA approval of tavaborole for the treatment of onychomycosis and bortezomib for multiple myeloma. The antimicrobial and anticancer effects of organoboron compounds motivate the investigation of the effects of the novel derivatives described here. A total of fourteen new boronic derivatives were synthesized and characterized using analytical methods. The antimicrobial activities were evaluated against M. tuberculosis (Mtb) H37Rv strains and fungal dermatophytes (C. albicans, ATCC 90028; T. rubrum, ATCC 28189; and T. mentagrophytes, ATCC 11481), while the anticancer effect was evaluated against oral squamous cell carcinoma (SCC) cell lines. Several promising boron-containing prototypes were identified, providing a foundation for further molecular optimization in the development of new antimicrobial and anticancer compounds. Full article

The wide use of boronic compounds, especially boronic acids and benzoxaboroles, in virtually all fields of chemistry is related to their specific properties. The most important of them are the ability to form cyclic esters with diols and the complexation of anions. In both cases, the equilibrium of the reaction depends mainly on the acidity of the compounds, although other factors must also be taken into account. Quantification of the acidity (pK_a value) is a fundamental factor considered when designing new compounds of practical importance. The aim of the current work was to collect available values of the acidity constants of monosubstituted phenylboronic acids, critically evaluate these data, and supplement the database with data for missing compounds. Measurements were made using various methods, as a result of which a fast and reliable method for determining the pK_a of boronic compounds was selected. For an extensive database of monosubstituted phenylboronic acids, their correlation with their Brønsted analogues—namely carboxylic acids—was examined. Compounds with ortho substituents do not show any correlation, which is due to the different natures of both types of acids. Nonetheless, both meta- and para-substituted compounds show excellent correlation. From a practical point of view, acidity constants are best determined from the Hammett equation. Computational approaches for determining acidity constants were also analyzed. In general, the reported calculated values are not compatible with experimental ones, providing comparable results only for selected groups of compounds. Full article

Pleuromutilins are a group of antibiotics derived from the naturally occurring compound. The recent approval of lefamulin for both intravenous and oral doses in humans to treat community-acquired bacterial pneumonia has prompted investigations in modifying the structure to broaden the antibacterial spectrum, enhance the activity, and improve the pharmacokinetic properties. AN11251 is a C(14)-functionalized pleuromutilin with a boron-containing heterocycle substructure. It was demonstrated to be an anti-Wolbachia agent with therapeutic potential for Onchocerciasis and lymphatic filariasis. Here, the in vitro and in vivo PK parameters of AN11251 were measured including PPB, intrinsic clearance, half-life, systemic clearance, and volume of distribution. The results indicate that the benzoxaborole-modified pleuromutilin possesses good ADME and PK properties. AN11251 has potent activities against the Gram-positive bacterial pathogens tested, including various drug-resistant strains, and against the slow-growing mycobacterial species. Finally, we employed PK/PD modeling to predict the human dose for treatment of disease caused by Wolbachia, Gram-positive bacteria, or Mycobacterium tuberculosis, which might facilitate the further development of AN11251. Full article

Antimicrobial-resistant (AMR) bacteria have become a critical global issue in recent years. The inefficacy of antimicrobial agents against AMR bacteria has led to increased difficulty in treating many infectious diseases. Analyses of the environmental distribution of bacteria are important for monitoring the AMR problem, and a rapid as well as viable pH- and temperature-independent bacterial separation method is required for collecting and concentrating bacteria from environmental samples. Thus, we aimed to develop a useful and selective bacterial separation method using a chemically synthesized nanoprobe. The metal-free benzoxaborole-based dendrimer probe BenzoB-PAMAM(+), which was synthesized from carboxy-benzoxaborole and a poly(amidoamine) (PAMAM) dendrimer, could help achieve Gram-positive bacterial separation by recognizing Gram-positive bacterial surfaces over a wide pH range, leading to the formation of large aggregations. The recognition site of benzoxaborole has a desirable high acidity and may therefore be responsible for the improved Gram-positive selectivity. The Gram-positive bacterial aggregation was then successfully collected by using a 10 μm membrane filter, with Gram-negative bacteria remaining in the filtrate solution. BenzoB-PAMAM(+) will thus be useful for application in biological analyses and could contribute to further investigations of bacterial distributions in environmental soil or water. Full article

Tuberculosis remains a serious killer among infectious diseases due to its incidence, mortality, and occurrence of resistant mycobacterial strains. The challenge to discover new antimycobacterial agents forced us to prepare a series of N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)(hetero)aryl-2-carboxamides 1–19 via the acylation of 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol with various activated (hetero)arylcarboxylic acids. These novel compounds have been tested in vitro against a panel of clinically important fungi and bacteria, including mycobacteria. Some of the compounds inhibited the growth of mycobacteria in the range of micromolar concentrations and retained this activity also against multidrug-resistant clinical isolates. Half the maximal inhibitory concentrations against the HepG2 cell line indicated an acceptable toxicological profile. No growth inhibition of other bacteria and fungi demonstrated selectivity of the compounds against mycobacteria. The structure–activity relationships have been derived and supported with a molecular docking study, which confirmed a selectivity toward the potential target leucyl-tRNA synthetase without an impact on the human enzyme. The presented compounds can become important materials in antimycobacterial research. Full article

Oxidative stress is considered as a major factor causing retinal pigment epithelium (RPE) dysfunction and finally leading to retinal diseases such as age-related macular degeneration (AMD). Developing hydrogels for RPE cell delivery, especially those with antioxidant feature, is emerging as a promising approach for AMD treatment. Herein, a readily prepared antioxidant alginate-based hydrogel was developed to serve as a cytoprotective agent for RPE cells against oxidative damage. Alg-BOB was synthesized via conjugation of benzoxaborole (BOB) to the polysaccharide backbone. Hydrogels were formed through self-crosslinking of Alg-BOB based on benzoxaborole-diol complexation. The resulting hydrogel showed porous micro-structure, pH dependent mechanical strength and excellent self-healing, remolding, and injectable properties. Moreover, the hydrogel exhibited excellent cytocompatibility and could efficiently scavenge reactive oxygen species (ROS) to achieve an enhanced viability of ARPE-19 cells under oxidative condition. Altogether, our study reveals that the antioxidant Alg-BOB hydrogel represents an eligible candidate for RPE delivery and AMD treatment. Full article

The current study is focused on the combination of pyrazinamide with 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol, which is a crucial pharmacophore of several antimicrobial agents. The use of benzoxaborole moiety could afford the formation of a spiro adduct between benzoxaborole moiety and 3'-terminal adenosine nucleotide Ade76 of tRNA^Leu. In the form of this spiro adduct, it may potentially inhibit the enzyme leucyl-tRNA synthetase (LeuRS). A large heterocyclic substitution in position 6 of the benzoxaborole moiety could lead to the enhanced selectivity of the intended compounds to the bacterial enzyme due to steric clashes with eukaryotic types of LeuRS. The target compounds were synthesized by condensation of 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol with variously substituted heteroaromatic acids that underwent previous activation. The synthetic products and the isolated condensation intermediates were subjected to biological in vitro screening against fungi and bacteria, including mycobacteria and in vitro cytotoxicity screening against the HepG2 cancer cell line. Some of the compounds showed moderate antimycobacterial activity with persisted low toxicity. Full article

Fluorinated boron species are a very important group of organoboron compounds used first of all as receptors of important bioanalytes, as well as biologically active substances, including Tavaborole as an antifungal drug. The presence of substituents containing fluorine atoms increases the acidity of boronic compounds, which is crucial from the point of view of their interactions with analytes or certain pathogen’s enzymes. The review discusses the electron acceptor properties of fluorinated boronic species using both the acidity constant (pK_a) and acceptor number (AN) in connection with their structural parameters. The NMR spectroscopic data are also presented, with particular emphasis on ¹⁹F resonance due to the wide range of information that can be obtained from this technique. Equilibria in solutions, such as the dehydration of boronic acid to form boroxines and their esterification or cyclization with the formation of 3-hydroxyl benzoxaboroles, are discussed. The results of the latest research on the biological activity of boronic compounds by experimental in vitro methods and theoretical calculations using docking studies are also discussed. Full article

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. Full article

In this review, the history of boron’s early use in drugs, and the history of the use of boron functional groups in medicinal chemistry applications are discussed. This includes diazaborines, boronic acids, benzoxaboroles, boron clusters, and carboranes. Furthermore, critical developments from these functional groups are highlighted along with recent developments, which exemplify potential prospects. Lastly, the application of boron in the form of a prodrug, softdrug, and as a nanocarrier are discussed to showcase boron’s emergence into new and exciting fields. Overall, we emphasize the evolution of organoboron therapeutic agents as privileged structures in medicinal chemistry and outline the impact that boron has had on drug discovery and development. Full article

Benzoxaboroles have emerged over the past decade mainly due to their growing medicinal importance. Regarding the wide application of IR spectroscopy in the pharmaceutical industry, the vibrational properties of over a dozen of benzoxaboroles were described, based on results of DFT calculations as well as IR and Raman spectra measurements. Investigated series of compounds included the currently available antifungal drug (Tavaborole, AN2690) as well as its derivatives. An intense and well-isolated band corresponding to the B-OH group stretching vibrations was present in all experimental IR spectra in the range of 1446–1414 cm⁻¹ and can be considered as characteristic for benzoxaboroles. The vibrational properties of benzoxaboroles are shown to be affected by the formation of intramolecular as well as intermolecular hydrogen bonds, which should also influence the interactions of benzoxaboroles with biomolecules and impact on their biological functions. Docking studies of the benzoxaboroles’ adenosine monophosphate (AMP) spiroboronates into the Candida albicans leucyl-RS synthetase binding pocket showed that the introduction of an amine substituent has a strong influence on their binding. The determined values of inhibition constants manifest high potential of some of the investigated molecules as possible inhibitors of that enzyme. Full article

The review covers the chemistry of organoboron heterocycles structurally related to benzoxaboroles where one of the carbon atoms in a boracycle or a fused benzene ring is replaced by a heteroelement such as boron, silicon, tin, nitrogen, phosphorus, or iodine. Related ring expanded systems including those based on naphthalene and biphenyl cores are also described. The information on synthetic methodology as well as the basic structural and physicochemical characteristics of these emerging heterocycles is complemented by a presentation of their potential applications in organic synthesis and medicinal chemistry, the latter aspect being mostly focused on the promising antimicrobial activity of selected compounds. Full article