Search Results (20)

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

Background: Due to chronic venous insufficiency, venous leg ulcers (VLUs) develop as chronic wounds characterized by impaired healing, persistent inflammation, and endothelial dysfunction. Nitrosative stress, mitochondrial damage, and tissue apoptosis caused by excess nitric oxide (NO) produced by iNOS in macrophages and fibroblasts are contributing factors in the chronic wound environment; therefore, pharmacological modulation of iNOS presents an attractive mechanistic target in chronic wound pathophysiology. Methods: Herein, we present the use of a structure-based computational strategy to assess the inhibition of tavaborole, a boron-based antifungal agent, against iNOS using human iNOS crystal structure (PDB ID: iNOS) by molecular docking using AutoDock 4.2, 500 ns simulation of molecular dynamics (MD), with equilibration within ~50 ns and analyses over full trajectory and binding free energy calculations through the MM-PBSA approach. Results: Docking studies showed favorable binding of tavaborole (–6.1 kcal/mol) in the catalytic domain, which stabilizes contacts with several key residues (CYS200, PRO350, PHE369, GLY371, TRP372, TYR373, and GLU377). MD trajectories for 1 ns showed stable structural configurations with negligible deviations (RMSD ≈ 0.44 ± 0.10 nm) and hydrogen bonding, and MM-PBSA analysis confirmed energetically favorable complex formation (ΔG_binding ≈ 18.38 ± 63.24 kJ/mol) similar to the control systems (L-arginine and 1400W). Conclusions: Taken together, these computational findings indicate that tavaborole can stably occupy the iNOS active site and interact with key catalytic residues, providing a mechanistic basis for further in vitro and ex vivo validation of its potential as an iNOS inhibitor to reduce nitrosative stress and restore endothelial homeostasis in venous leg ulcers, rather than direct therapeutic proof. Full article

Boron-containing compounds have made a significant impact on the field of medicinal chemistry since the discovery of Bortezomib (Velcade^®), a dipeptide boronic acid approved by the FDA in 2003 for the treatment of multiple myeloma. Since then, over the last two decades, four more boron-containing drugs have been approved by the FDA: Tavaborole (Kerydin^®), Ixazomib (Ninlaro^®), Crisaborole (Eucrisa^®), and Vaborbactam (in Vabomere^®). These compounds are approved for treating conditions such as onychomycosis, multiple myeloma, and atopic dermatitis, as well as an Aβ-lactamase inhibitor approved in combination with meropenem for treating infections. Further, many organic molecules containing boron are in clinical trials. Additionally, boron-containing compounds play a crucial role in various biological processes. Boron’s Lewis acidity has been utilized for diverse applications, from targeting biological molecules to the synthesis of organic compounds and in advanced drug delivery systems. Recent progress in the advancement of boron-containing compounds has not stopped, and the further use of Boron is emerging day-by-day with the discovery of multifaceted applications. This review aims to highlight the recent advances made in the last decade in the drug design of boron-containing compounds and their therapeutic applications. Here, in this work, we have focused on the recent diversification and progress of boron-containing compounds in medicinal chemistry applications. Full article

Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene–maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which exhibited tumor-targeted distribution via the enhanced permeability and retention (EPR) effect. Building upon this approach, in this study, we designed and synthesized a series of SMA-based polymeric probes for BNCT and evaluated their biological activities, with a particular focus on tumor-targeting properties. Methods: Two SMA-based BNCT nanoprobes, SMA–glucosamine conjugated Borax (SG@B) and SMA-conjugated aminophenylboronic acid encapsulating tavaborole (S-APB@TB), were designed and synthesized. The boron content in the conjugates was quantified using inductively coupled plasma mass spectrometry (ICP-MS), while particle sizes were measured via dynamic light scattering (DLS). In vitro cytotoxicity was assessed using the MTT assay in mouse colon cancer C26 cells. The tissue distribution of the conjugates was analyzed in a mouse sarcoma S180 solid tumor model using ICP-MS. Results: Both SG@B and S-APB@TB formed nanoformulations with average particle sizes of 137 nm and 99 nm, respectively. The boron content of SG@B was 2%, whereas S-APB@TB exhibited a significantly higher boron content of 14.4%. Both conjugates demonstrated dose-dependent cytotoxicity against C26 cells, even in the absence of neutron irradiation. Notably, tissue distribution analysis following intravenous injection revealed higher boron concentrations in plasma and tumor tissues compared to most normal tissues, with S-APB@TB showing particularly favorable tumor accumulation. Conclusions: These findings highlight the tumor-targeting potential of SMA-based BNCT nanoprobes. Further investigations are warranted to advance their clinical development as BNCT agents. 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

Onychomycosis is a common nail disease caused by fungi. The primary pathogens are dermatophytes; however, yeasts, non-dermatophyte moulds, and mixed fungal populations may also contribute to the development of a recalcitrant condition, usually accompanied by difficulties in everyday life and severe emotional stress. Treatment failure and relapse of the infection are the most frequent problems, though new issues have become the new challenges in the therapeutic approach to onychomycosis. Resistance to antifungals, an increasing number of comorbidities, and polydrug use among the ageing population are imperatives that impose a shift to safer drugs. Topical antifungals are considered less toxic and minimally interact with other drugs. The development of new topical drugs for onychomycosis is driven by the unmet need for effective agents with prolonged post-treatment disease-free time and a lack of systemic impact on the patients’ health. Efinaconazole, Tavaborole, and Luliconazole have been added to physicians’ weaponry during the last decade, though launched on the market of a limited number of countries. The pipeline is either developing new products (e.g., ME-1111 and NP213) with an appealing combination of pharmacokinetic, efficacy, and safety properties or reformulating old, well-known drugs (Terbinafine and Amphotericin B) by using new excipients as penetration enhancers. Full article

Background: Onychomycosis is the most common nail disease seen in clinical practice. Medication safety, severity of disease, comorbidities, concomitant medications, patient age, and cost are all important considerations when treating onychomycosis. Because cost may affect treatment decisions, we sought to analyze Medicaid formulary coverage of onychomycosis antifungals. Methods: Public state Medicaid formularies were searched for coverage of US Food and Drug Administration–approved onychomycosis medications and off-label oral fluconazole. Total drug cost for a single great toenail was calculated using the National Average Drug Acquisition Cost. Pearson correlation coefficients were calculated to compare coverage and cost, mycologic cure rate, and complete cure rate. Results: Oral terbinafine and off-label fluconazole were widely covered for onychomycosis treatment. There was poor coverage of oral itraconazole and topical ciclopirox, and there was no coverage of topical efinaconazole and tavaborole without step-edits or prior authorization. There was a significant negative correlation between medication coverage and cost (r = 20.758; P = .040). There was no correlation between medication coverage and mycologic (r = 0.548; P = .339) and complete (r = 0.768; P = .130) cure rates. Conclusions: There is poor Medicaid coverage of antifungals for the treatment of onychomycosis, with step-edits and prior authorization based on cost rather than treatment safety and efficacy. We recommend involving podiatrists and dermatologists in developing criteria for insurance approval of onychomycosis treatments. Full article

Dermatophytomas are characterized as a hyperkeratotic fungal mass in the subungual space, showing as dense white or yellow, typically in longitudinal streaks or patches. Masses can be visualized by traditional microscopy or histology. Newer technologies such as dermoscopy and optical coherence tomography also provide visual features for dermatophytoma diagnosis. The density of fungal mass, and lack of adherence to the nail structures, as well as possible biofilm development, may play a role in the reduction in drug penetration and subsequent lack of efficacy with traditional oral therapies such as terbinafine and itraconazole. A combination of drug treatment with mechanical or chemical debridement/avulsion has been recommended to increase efficacy. The topical antifungal solutions such as tavaborole, efinaconazole, and luliconazole may reach the dermatophytoma by both the transungual and subungual routes, due to low affinity for keratin and low surface tension. Current data indicates these topicals may provide efficacy for dermatophytoma treatment without debridement/avulsion. Similarly, fosravuconazole (F-RVCZ) has an improved pharmacological profile versus ravuconazole and may be an improved treatment option versus traditional oral therapies. The availability of improved treatments for dermatophytomas is crucial, as resistance to traditional therapies is on the increase. 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

Onychomycosis is a prominent fungal infection that causes discoloration, thickening, and mutilation leading to the separation of the nail from the nail bed. Treatment modalities for onychomycosis may include oral, topical, or combination therapy with antifungals and at times may require chemical or surgical intervention. The burden of side effects of antifungals is enormous, and therefore using molecular docking-based drug selection in context with the target keratin protein would ensure better disease management. Ciclopirox, Amorolfine HCl, Efinaconazole, Tioconazole, and Tavaborole were submitted for assessment, revealing that Amorolfine HCl is the best fit. Consequently, two formulations (Nail lacquer and nanoemulgel) were developed from Amorolfine HCl to validate the in silico screening outcomes. The formulations were further fortified with over-the-counter ingredients vis-a-vis with vitamin E in nail lacquer and undecylenic acid in nanoemulgel for their prominent roles in improving nail health. Both the formulations were systematically designed, optimized, and characterized. Amorolfine HCl containing nanoemulgel (NEG) was developed using undecylenic acid as an oil phase and thioglycolic acid as a penetration enhancer. The quality parameters evaluated were particle size, the zeta potential for nanoemulsion (NE) (78.04 ± 4.724 nm and −0.7mV, respectively), in vitro cumulative drug release (96.74% for NE and 88.54% for NEG), and transungual permeation (about 73.49% for NEG and 54.81% for NE). Nail lacquer was evaluated for the drying time, non-volatile content, and blush test. In vitro cumulative drug release of the developed nail lacquer and comparator marketed formulations were around 81.5% and 75%, respectively. Similarly, the transungual drug permeation was 6.32 μg/cm² and 5.89 μg/cm², respectively, in 24 h. The in silico guided preparation of both formulations containing Amorolfine HCl and over the counter ingredients is amenable for therapeutic use against onychomycosis and will be evaluated in the in vivo model. 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 unique electron deficiency and coordination property of boron led to a wide range of applications in chemistry, energy research, materials science and the life sciences. The use of boron-containing compounds as pharmaceutical agents has a long history, and recent developments have produced encouraging strides. Boron agents have been used for both radiotherapy and chemotherapy. In radiotherapy, boron neutron capture therapy (BNCT) has been investigated to treat various types of tumors, such as glioblastoma multiforme (GBM) of brain, head and neck tumors, etc. Boron agents playing essential roles in such treatments and other well-established areas have been discussed elsewhere. Organoboron compounds used to treat various diseases besides tumor treatments through BNCT technology have also marked an important milestone. Following the clinical introduction of bortezomib as an anti-cancer agent, benzoxaborole drugs, tavaborole and crisaborole, have been approved for clinical use in the treatments of onychomycosis and atopic dermatitis. Some heterocyclic organoboron compounds represent potentially promising candidates for anti-infective drugs. This review highlights the clinical applications and perspectives of organoboron compounds with the natural boron atoms in disease treatments without neutron irradiation. The main topic focuses on the therapeutic applications of organoboron compounds in the diseases of tuberculosis and antifungal activity, malaria, neglected tropical diseases and cryptosporidiosis and toxoplasmosis. Full article

To evaluate the combination effects of anti-onychomycosis drugs, the minimum inhibitory concentrations of topical (efinaconazole, luliconazole, and tavaborole) and oral (itraconazole and terbinafine) drugs for Trichophyton rubrum and Trichophyton interdigitale (8 each, with a total of 16 strains) were determined using the microdilution checkerboard technique based on the Clinical and Laboratory Standard Institute guidelines. No antagonism was observed between the topical and oral drugs against all the tested strains. Efinaconazole with terbinafine exerted a synergistic effect on 43.8% of the strains tested (7/16 strains) and efinaconazole with itraconazole on 12.5% (2/16 strains). Conversely, luliconazole showed no synergistic effect with terbinafine but was synergistically effective with itraconazole against 31.3% of the strains (5/16 strains). Tavaborole showed no synergistic effect with terbinafine and was synergistically effective with itraconazole against 18.8% of the strains (3/16 strains). The results suggest that a combination of topical and oral drugs could be a potential clinical option for onychomycosis treatment, and overall, the efinaconazole and oral drug combination would be the most advantageous among the tested combinations. Full article

Benzoxaboroles emerged recently as molecules of high medicinal potential with Kerydin^® (Tavaborole) and Eucrisa^® (Crisaborole) currently in clinical practice as antifungal and anti-inflammatory drugs, respectively. Over a dozen of 3-amino benzoxaboroles, including Tavaborole’s derivatives, have been synthetized and characterized in terms of their activity against Candida albicans as a model pathogenic fungus. The studied compounds broaden considerably the structural diversity of reported benzoxaboroles, enabling determination of the influence of the introduction of a heterocyclic amine, a fluorine substituent as well as the formyl group on antifungal activity of those compounds. The determined zones of the growth inhibition of examined microorganism indicate high diffusion of majority of the studied compounds within the applied media as well as their reasonable activity. The Minimum Inhibitory Concentration (MIC) values show that the introduction of an amine substituent in position “3” of the benzoxaborole heterocyclic ring results in a considerable drop in activity in comparison with Tavaborole (AN2690) as well as unsubstituted benzoxaborole (AN2679). In all studied cases the presence of a fluorine substituent at position para to the boron atom results in lower MIC values (higher activity). Interestingly, introduction of a fluorine substituent in the more distant piperazine phenyl ring does not influence MIC values. As determined by X-ray studies, introduction of a formyl group in proximity of the boron atom results in a considerable change of the boronic group geometry. The presence of a formyl group next to the benzoxaborole unit is also detrimental for activity against Candida albicans. Full article