RESUMEN
Fungal infections are very alarming nowadays and are common throughout the world. Severe fungal infections may lead to a significant risk of mortality and morbidity worldwide. Sustained delivery of antifungal agents is needed to mitigate this problem. In the current study, an attempt has been made to formulate griseofulvin-loaded nanosponges using the quasi-emulsion solvent diffusion technique. For characterization, griseofulvin loaded nanosponges were tested by different instrumental techniques such as optical microscopy, scanning electron microscopy (SEM), powder X-ray diffractometer (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). The antifungal activity of the nanosponges was assessed against Candida albican strain using the agar well-diffusion method. Finally, the drug-loaded nanosponges' in vitro sustained release activity was evaluated. FTIR spectra showed no chemical interference between the drug and polymers. Some of the peaks of the drug are not visible in the FTIR spectrum, which suggests drug entrapment. PXRD data showed that the drug lost its high crystallinity when entrapped in the nanosponge matrix. From the morphological studies via SEM and TEM, a brief idea of the surface morphology of the nanosponges was obtained. The small pores throughout the structure proved its high porosity. The antifungal sensitivity assay was successful, and a zone of inhibition was observed in all the formulations. The in-vitro drug release study showed sustained behaviour. The sustaining effect was due to the polymer and cross-linker used, which gave rise to a porous scaffold matrix. From the results, it can be concluded that griseofulvin-loaded nanosponges can be used for antifungal drug delivery against various topical skin infections.
Asunto(s)
Antifúngicos , Celulosa , Preparaciones de Acción Retardada , Liberación de Fármacos , Griseofulvina , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/administración & dosificación , Griseofulvina/química , Griseofulvina/farmacología , Griseofulvina/administración & dosificación , Celulosa/química , Celulosa/análogos & derivados , Portadores de Fármacos/química , Espectroscopía Infrarroja por Transformada de Fourier , Sistemas de Liberación de Medicamentos , Administración Tópica , Pruebas de Sensibilidad Microbiana , Nanopartículas/química , Rastreo Diferencial de CalorimetríaRESUMEN
INTRODUCTION: Tinea capitis, a common scalp infection primarily affecting children, is caused by keratinophilic dermatophytic fungi, notably Microsporum and Trichophyton species. Microsporum canis, primarily transmitted from cats and dogs to humans, is rarely reported in non-endemic regions like India. We report a cases involving three family members from Delhi, India, diagnosed with tinea capitis caused by Microsporum canis. The index case, a five-year-old boy, contracted the infection through contact with a cat, while his younger brother and sister acquired it through human-to-human transmission within the family. METHODS: Clinical examination, microscopic analysis, and molecular identification techniques confirmed the diagnosis. Antifungal susceptibility testing revealed sensitivity to itraconazole and terbinafine but resistance to griseofulvin. RESULTS: Treatment with oral terbinafine and topical ketoconazole cream led to successful outcomes for all three patients. Molecular typing confirmed clonality of the isolates, indicating human-to-human transmission. CONCLUSION: This case study underscores the significance of considering atypical sources of infection and human-to-human transmission in the diagnosis and management of tinea capitis caused by Microsporum canis in non-endemic regions. It emphasizes the necessity of thorough contact history assessment and appropriate antifungal therapy for effective control of the infection.
Asunto(s)
Antifúngicos , Microsporum , Terbinafina , Tiña del Cuero Cabelludo , Humanos , Microsporum/genética , Microsporum/aislamiento & purificación , Microsporum/clasificación , Microsporum/efectos de los fármacos , Tiña del Cuero Cabelludo/microbiología , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/diagnóstico , Masculino , India , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Preescolar , Terbinafina/uso terapéutico , Gatos , Femenino , Animales , Pruebas de Sensibilidad Microbiana , Itraconazol/uso terapéutico , Naftalenos/uso terapéutico , Naftalenos/farmacología , Resultado del Tratamiento , Cetoconazol/uso terapéutico , Tipificación Molecular , Familia , Niño , Griseofulvina/uso terapéuticoRESUMEN
BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.
Asunto(s)
Antifúngicos , Brotes de Enfermedades , Farmacorresistencia Fúngica , Pruebas de Sensibilidad Microbiana , Microsporum , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Humanos , Microsporum/efectos de los fármacos , Masculino , Femenino , Dinamarca/epidemiología , Adulto , Niño , Terbinafina/farmacología , Terbinafina/uso terapéutico , Persona de Mediana Edad , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/microbiología , Tiña del Cuero Cabelludo/epidemiología , Griseofulvina/farmacología , Griseofulvina/uso terapéutico , Preescolar , Adolescente , Adulto Joven , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/epidemiología , Itraconazol/farmacología , Itraconazol/uso terapéutico , Anciano , Fluconazol/farmacología , Fluconazol/uso terapéuticoRESUMEN
Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 â below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.
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Cristalización , Griseofulvina , Polímeros , Temperatura de Transición , Griseofulvina/química , Cristalización/métodos , Polímeros/química , Estabilidad de Medicamentos , Enlace de Hidrógeno , Polivinilos/química , Polietilenglicoles/química , Povidona/química , Vidrio/químicaRESUMEN
A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gαi2 inhibitor, GT-14, in rat plasma using a SCIEX 6500+ triple QUAD LC-MS system equipped with an ExionLC UHPLC unit. GT-14 (m/z 265.2 â 134.1) and griseofulvin (Internal Standard, IS) (m/z 353.1 â 285.1) were detected in a positive mode by electrospray ionization (ESI) using multiple reaction monitoring (MRM). The assay was linear in the concentration range of 0.78-1000â¯ng/mL in rat plasma. Both accuracy and precision values were within the acceptance criteria of ±15 %, as established by FDA guidance. The matrix effect was negligible from plasma, with signal percentages of 98.5-106.9 %. The mean recovery was 104.5 %, indicating complete extraction of GT-14 from plasma. GT-14 was found to be stable under different experimental conditions. The validated method was successfully applied to evaluate plasma protein binding and in vivo pharmacokinetics of GT-14 in rats.
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Griseofulvina , Animales , Masculino , Ratas , Griseofulvina/farmacocinética , Griseofulvina/sangre , Cromatografía Líquida con Espectrometría de Masas , Unión Proteica , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (Tg) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy.
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Cristalización , Estabilidad de Medicamentos , Griseofulvina , Griseofulvina/química , Derivados de la Hipromelosa/química , Difracción de Rayos X/métodos , Solubilidad , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Temperatura , HumedadRESUMEN
The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.
Asunto(s)
Hongos , Fungicidas Industriales , Griseofulvina , Enfermedades de las Plantas , Griseofulvina/farmacología , Griseofulvina/química , Griseofulvina/síntesis química , Fungicidas Industriales/farmacología , Fungicidas Industriales/síntesis química , Fungicidas Industriales/química , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Hongos/efectos de los fármacos , Simulación del Acoplamiento Molecular , Solanum lycopersicum/microbiología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/químicaRESUMEN
This study aimed to evaluate the current management of tinea capitis in the United States, specifically focusing on patients aged 0-2 months, 2 months to 2 years, and 2 years to 18 years. An online survey, distributed through the Pediatric Dermatology Research Alliance and the Society of Pediatric Dermatology, revealed the following preferences: fluconazole for those under 2 months, griseofulvin for those aged 2 months to 2 years, and terbinafine for those aged 2 years and older. There exists inter-provider variation in tinea capitis treatment regimens within the pediatric dermatology community.
Asunto(s)
Antifúngicos , Tiña del Cuero Cabelludo , Lactante , Niño , Humanos , Estados Unidos/epidemiología , Antifúngicos/uso terapéutico , Itraconazol , Dermatólogos , Naftalenos , Tiña del Cuero Cabelludo/diagnóstico , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/epidemiología , Griseofulvina/uso terapéuticoRESUMEN
3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low-dose and low-bias 3D ED protocol has been implemented to identify six phases from a multiple-phase melt-crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low-dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell parameters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF-PEG IC-I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF-PEG IC-II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF-PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam-sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.
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Electrones , Polímeros , Polímeros/química , Griseofulvina/química , Polietilenglicoles/química , Cristalización/métodosRESUMEN
Co-amorphous systems (CAMS) were developed between griseofulvin (GRI) and L-leucine (LEU) at 2:1 wt ratio, by application of a novel solvent assisted hot-melt extrusion (HME) method that involved wet processing/drying of the feeds prior to extrusion. CAMS formation was confirmed by powder crystallography (pXRD) and thermal analysis (DSC). Intermolecular H-bonding between the carbonyl groups of GRI and the hydroxyl and amino groups of LEU were identified by vibrational spectroscopy (ATR-FTIR). The measured glass transition temperatures (Tg) of the extrudates from feeds processed with aqueous acetic acid (AcOH) were markedly lower than that of neat amorphous GRI and values predicted from Gordon-Taylor equation, indicating plasticizing action of AcOH. Drug concentrations during dissolution of CAMS under non-sink conditions (Sink Index 0.0115) were up to x82 higher at plateau compared to crystalline drug solubility. The degree of supersaturation lasted for at least 24 h. Plasticizer (Compritol®/Kolliphor® 75/25) added before extrusion did not impact significantly on CAMS formation but altered the dissolution profile from a spring-and-parachute profile to gradual rise to maximum. These findings reinforce the application of drug/amino acid-based CAMS in formulation, particularly for high-dose drugs, for which polymers are unsuited due to the required large proportions.
Asunto(s)
Griseofulvina , Polímeros , Griseofulvina/química , Solventes , Polímeros/química , Solubilidad , Vidrio , Composición de Medicamentos/métodos , CalorRESUMEN
In response to the urgent demand for innovative antibiotics, theoretical investigations have been employed to design novel analogs. Because griseofulvin is a potential antibacterial agent, we have designed novel derivatives of griseofulvin to enhance its antibacterial efficacy and to evaluate their interactions with bacterial targets using in silico analysis. The results of this study reveal that the newly designed derivatives displayed the most robust binding affinities towards PBP2, tyrosine phosphatase, and FtsZ proteins. Additionally, molecular dynamics (MD) simulations underscored the notable stability of these derivatives when engaged with the FtsZ protein, as evidenced by root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and solvent-accessible surface area (SASA). Importantly, this observation aligns with expectations, considering that griseofulvin primarily targets microtubules in eukaryotic cells, and FtsZ functions as the prokaryotic counterpart to microtubules. These findings collectively suggest the promising potential of griseofulvin and its designed derivatives as effective antibacterial agents, particularly concerning their interaction with the FtsZ protein. This research contributes to the ongoing exploration of novel antibiotics and may serve as a foundation for future drug development efforts.
Asunto(s)
Griseofulvina , Simulación de Dinámica Molecular , Simulación del Acoplamiento Molecular , Griseofulvina/farmacología , Antibacterianos/farmacología , Desarrollo de MedicamentosRESUMEN
Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults. nAMD is treated with biologics targeting vascular endothelial growth factor; however, many patients do not respond to the current therapy. Here, a small molecule drug, griseofulvin (GRF), is used due to its inhibitory effect on ferrochelatase, an enzyme important for choroidal neovascularization (CNV). For local and sustained delivery to the eyes, GRF is encapsulated in microparticles based on poly(lactide-co-glycolide) (PLGA), a biodegradable polymer with a track record in long-acting formulations. The GRF-loaded PLGA microparticles (GRF MPs) are designed for intravitreal application, considering constraints in size, drug loading content, and drug release kinetics. Magnesium hydroxide is co-encapsulated to enable sustained GRF release over >30 days in phosphate-buffered saline with Tween 80. Incubated in cell culture medium over 30 days, the GRF MPs and the released drug show antiangiogenic effects in retinal endothelial cells. A single intravitreal injection of MPs containing 0.18 µg GRF releases the drug over 6 weeks in vivo to inhibit the progression of laser-induced CNV in mice with no abnormality in the fundus and retina. Intravitreally administered GRF MPs prove effective in preventing CNV, providing proof-of-concept toward a novel, cost-effective nAMD therapy.
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Neovascularización Coroidal , Griseofulvina , Ratones , Humanos , Animales , Anciano , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Griseofulvina/farmacología , Griseofulvina/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/prevención & controlRESUMEN
BACKGROUND: The number of terbinafine-resistant Trichophyton indotineae is increasing in recent years while the treatment is still a matter to discuss. OBJECTIVES: To explore the best therapeutic approach, we present real-world treatment of T. indotineae infection by analysing publicly available data. METHODS: We have reviewed all published articles, mainly including case reports and case series, on the drug-resistant T. mentagrophytes complex by using the key search terms to search the databases. RESULTS: We enrolled 25 articles from 14 countries, including 203 times of treatment information for 113 patients. The cure rate of itraconazole 200 mg per day at the fourth, eighth and the twelfth week were 27.27%, 48.48% and 54.55%, respectively, which was significantly higher than terbinafine 250 mg per day (8.77%, 24.56% and 28.07%) and even 500 mg/d terbinafine. Griseofulvin 500-1000 mg for 2-6 months may be effective while fluconazole had no record of successful treatment. Voriconazole and ravuconazole had potential therapeutic efficacy. Topical therapy alone showed limited therapeutic efficacy, but the combination with oral antifungals can be alternative. CONCLUSION: Oral itraconazole 200 mg per day for 4-8 weeks was the most effective treatment out of these commonly used antifungal drugs, and can be prior selection.
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Itraconazol , Naftalenos , Tiña , Humanos , Itraconazol/farmacología , Terbinafina/uso terapéutico , Terbinafina/farmacología , Estudios Retrospectivos , Naftalenos/farmacología , Antifúngicos/farmacología , Trichophyton , Griseofulvina/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Our previous work shows that ß-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for more than 12 months. The stability is probably due to hydrogen bond networks spread throughout the ASD, facilitated by the indomethacin which has both hydrogen donors and acceptors. To investigate the stabilization mechanisms further, here we tested five other drug molecules, including two without any hydrogen bond donors. A combination of experimental techniques (differential scanning calorimetry, X-ray power diffraction) and molecular dynamics simulations was used to find the maximum drug loadings for ASDs with furosemide, griseofulvin, ibuprofen, ketoconazole and rifaximin. This approach revealed the underlying stabilization factors and the capacity of computer simulations to predict ASD stability. We searched the ASD models for crystalline patterns, and analyzed diffusivity of the drug molecules and hydrogen bond formation. ASDs loaded with rifaximin and ketoconazole remained stable for at least 12 months, even at 90 % drug loading, whereas stable drug loadings for furosemide, griseofulvin and ibuprofen were at a maximum of 70, 50 and 40 %, respectively. Steric confinement and hydrogen bonding to the proteins were the most important stabilization mechanisms at low drug loadings (≤ 40 %). Inter-drug hydrogen bond networks (including those with induced donors), ionic interactions, and a high Tg of the drug molecule were additional factors stabilizing the ASDs at drug loading greater than 40 %.
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Ibuprofeno , Cetoconazol , Ibuprofeno/química , Furosemida , Lactoglobulinas , Griseofulvina , Rifaximina , Indometacina/química , Solubilidad , Composición de Medicamentos/métodosRESUMEN
The marine-derived fungal strains KMM 4718 and KMM 4747 isolated from sea urchin Scaphechinus mirabilis as a natural fungal complex were identified as Penicillium sajarovii and Aspergillus protuberus based on Internal Transcribed Spacer (ITS), partial ß-tubulin (BenA), and calmodulin (CaM) molecular markers as well as an ribosomal polymerase two, subunit two (RPB2) region for KMM 4747. From the ethyl acetate extract of the co-culture, two new polyketides, sajaroketides A (1) and B (2), together with (2'S)-7-hydroxy-2-(2'-hydroxypropyl)-5-methylchromone (3), altechromone A (4), norlichexanthone (5), griseoxanthone C (6), 1,3,5,6-tetrahydroxy-8-methylxanthone (7), griseofulvin (8), 6-O-desmethylgriseofulvin (9), dechlorogriseofulvin (10), and 5,6-dihydro-4-methyl-2H-pyran-2-one (11) were identified. The structures of the compounds were elucidated using spectroscopic analyses. The absolute configurations of the chiral centers of sajaroketides A and B were determined using time-dependent density functional theory (TDDFT)-based calculations of the Electronic Circular Dichroism (ECD) spectra. The inhibitory effects of these compounds on urease activity and the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans were observed. Sajaroketide A, altechromone A, and griseofulvin showed significant cardioprotective effects in an in vitro model of S. aureus-induced infectious myocarditis.
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Penicillium , Policétidos , Staphylococcus aureus , Estructura Molecular , Policétidos/química , Griseofulvina/farmacología , Hongos , Dicroismo CircularRESUMEN
Since griseofulvin was marketed as a non-polyene antifungal antibiotic drug in 1958, its poor water solubility has been an issue for its wide applications, and over the last sixty years, many attempts have been made to increase its water solubility; however, a significant result has yet to be achieved. Through supercritical carbon dioxide-assisted cyclodextrin complexation with the addition of a trace amount of water-soluble polymer surfactant, the griseofulvin inclusion complex with HP-γ-cyclodextrin was prepared and confirmed. The 1:2 ratio of griseofulvin and HP-γ-cyclodextrin in the complex was determined based on its NMR study. After complexation with HP-γ-cyclodextrin, griseofulvin's water solubility was increased 477 times compared with that of griseofulvin alone, which is the best result thus far. The complex showed 90% of griseofulvin release in vitro in 10 min, in an in vivo dog pharmacokinetic study; the Cmax was increased from 0.52 µg/mL to 0.72 µg/mL, AUC0-12 was increased from 1.55 µg·h/mL to 2.75 µg·h/mL, the clearance was changed from 51.78 L/kg/h to 24.16 L/kg/h, and the half-life time was changed from 0.81 h to 1.56 h, indicating the obtained griseofulvin complex can be a more effective drug than griseofulvin alone.
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Griseofulvina , gamma-Ciclodextrinas , Animales , Perros , Solubilidad , Dióxido de Carbono , Agua , 2-Hidroxipropil-beta-Ciclodextrina/químicaRESUMEN
BACKGROUND: Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. OBJECTIVE: This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. PATIENTS/METHODS: We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. RESULTS: Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. CONCLUSION: The over-crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine.
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Refugiados , Tiña del Cuero Cabelludo , Humanos , Niño , Griseofulvina/uso terapéutico , Terbinafina/uso terapéutico , Terbinafina/farmacología , Antifúngicos , Israel , Estudios Retrospectivos , Naftalenos/uso terapéutico , Tiña del Cuero Cabelludo/epidemiología , Microsporum , TrichophytonRESUMEN
Six griseofulvin analogues named penigriseofulvins A - F (1-6), including three undescribed compounds and three undescribed natural products, were isolated from the fungus Penicillium griseofulvum. Their structures and absolute configurations were determined by NMR spectroscopic analyses, HRESIMS, and X-ray diffraction experiments. All compounds were evaluated for their anti-inflammatory activity, of which compounds 1 and 4 showed potential anti-inflammatory effects in RAW264.7 macrophages and ulcerative colitis mice.
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Griseofulvina , Penicillium , Ratones , Animales , Griseofulvina/farmacología , Antiinflamatorios/farmacología , Penicillium/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Three previously undescribed griseofulvin derivatives, namely pochonichlamydins A-C, one small polyketide, namely pochonichlamydin D, together with nine known compounds, have been isolated from cultures of the fungus Pochonia chlamydosporia. Their structures with absolute configurations were elucidated on the basis of extensive spectrometric methods and single-crystal X-ray diffraction. Dechlorogriseofulvin and griseofulvin exhibited inhibitory activities against Candida albicans at the concentration of 100 µM, with inhibition rates of 69.1% and 56.3%, respectively. Meanwhile, pochonichlamydin C showed mild cytotoxicity against the human cancer MCF-7 cell line with an IC50 value of 33.1 µM.
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Hypocreales , Policétidos , Humanos , Policétidos/química , Griseofulvina , Células MCF-7RESUMEN
Griseofulvin was considered an effective agent for cancer therapy in past decades. Although the negative effects of griseofulvin on microtubule stability are known, the exact target and mechanism of action in plants remain unclear. Here, we used trifluralin, a well-known herbicide targeting microtubules, as a reference and revealed the differences in root tip morphology, reactive oxygen species production (ROS), microtubule dynamics, and transcriptome analysis between Arabidopsis treated with griseofulvin and trifluralin to elucidate the mechanism of root growth inhibition by griseofulvin. Like trifluralin, griseofulvin inhibited root growth and caused significant swelling of the root tip due to cell death induced by ROS. However, the presence of griseofulvin and trifluralin caused cell swelling in the transition zone (TZ) and meristematic zone (MZ) of root tips, respectively. Further observations revealed that griseofulvin first destroyed cortical microtubules in the cells of the TZ and early elongation zone (EZ) and then gradually affected the cells of other zones. The first target of trifluralin is the microtubules in the root MZ cells. Transcriptome analysis showed that griseofulvin mainly affected the expression of microtubule-associated protein (MAP) genes rather than tubulin genes, whereas trifluralin significantly suppressed the expression of αß-tubulin genes. Finally, it was proposed that griseofulvin could first reduce the expression of MAP genes, meanwhile increasing the expression of auxin and ethylene-related genes to disrupt microtubule alignment in root tip TZ and early EZ cells, induce dramatic ROS production, and cause severe cell death, eventually leading to cell swelling in the corresponding zones and inhibition of root growth.