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Chemical & Pharmaceutical Bulletin 2014Benzofuro[6,7-d]thiazoles, benzofuro[7,6-d]thiazoles and 6-arylaminobenzo[d]thiazole-4,7-diones were synthesized and tested for in vitro antifungal activity against...
Benzofuro[6,7-d]thiazoles, benzofuro[7,6-d]thiazoles and 6-arylaminobenzo[d]thiazole-4,7-diones were synthesized and tested for in vitro antifungal activity against Candida, Aspergillus species and Cryptococcus neoformans. Among them tested, many of synthesized compounds showed potent antifungal activity. The compounds 4d, 6e and 6h completely inhibited the growth of all Candida and Aspergillus species tested at the MIC level of 6.3 µg/mL. The results suggest that benzofuro[6,7-d]thiazoles and 6-arylaminobenzo[d]thiazole-4,7-diones would be promising antifungal agents.
Topics: Antifungal Agents; Aspergillus; Benzofurans; Candida; Cryptococcus neoformans; Microbial Sensitivity Tests; Thiazoles
PubMed: 24789966
DOI: 10.1248/cpb.c14-00146 -
Molecules (Basel, Switzerland) Jul 2020Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine's ability to permeate the human...
Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine's ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO laser. Structural changes of the nail barrier, induced by fractional CO laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied.
Topics: Administration, Topical; Adult; Allylamine; Animals; Antifungal Agents; Cattle; Drug Delivery Systems; Female; Hoof and Claw; Humans; Lacquer; Male; Middle Aged; Nails; Onychomycosis; Tissue Distribution
PubMed: 32635240
DOI: 10.3390/molecules25133043 -
BMC Complementary and Alternative... Nov 2015Combretum zeyheri, belongs to the family Combretaceae and is one of the most popular herbal plants in tropical and subtropical countries. The leaves of Combretum zeyheri...
BACKGROUND
Combretum zeyheri, belongs to the family Combretaceae and is one of the most popular herbal plants in tropical and subtropical countries. The leaves of Combretum zeyheri have been used as herbal medicine and have been reported to have pharmacological activity which includes anti-bacterial, anti-fungal, anticancer and antioxidant properties. The goal of this study was to isolate, identify and characterize compounds from C. zeyheri leaves which are responsible for its antifungal activity.
METHODS
The preliminary isolation of C. zeyheri active compounds was carried out using chromatographic techniques which include sephadex gel column chromatography, silica gel column chromatography and thin-layer chromatography (TLC). The isolated compounds were then investigated for their antifungal activity using broth dilution assay. The combined effect of the most potent compound and an antifungal drug miconazole was investigated using the checkerboard assay. Time-kill assays were conducted for the combinations using the colony counting method. The mechanism of action of 5-hydroxy-7,4'-dimethoxyflavone as a potent antifungal agent was investigated by determining its inhibitory activity on Candida albicans drug efflux pumps using the ciprofloxacin assay. The ability of 5-hydroxy-7,4'-dimethoxyflavone to inhibit antioxidant enzymes as well as the biosynthesis of ergosterol were also investigated.
RESULTS
A total of four pure compounds (A-D) were isolated from C. zeyheri leaf extract. Compound B (5-hydroxy-7,4'-dimethoxyflavone) was found to be active against Candida albicans using broth dilution method. This compound was also found to have synergistic activity on growth of C. albicans when combined with miconazole, completely inhibiting growth after only 4 hrs of incubation. Analysis of ergosterol content from Candida albicans showed a time-dependent decrease to 91 % and 63 % at 16 and 24 hrs respectively, in cells treated with ½ MIC of 5-hydroxy-7,4'-dimethoxyflavone. The compound 5-hydroxy-7,4'-dimethoxyflavone also showed inhibition of both the drug efflux pumps (with IC50 = 51.64 μg/ml) and the antioxidant enzymes (at 5 μM).
CONCLUSION
The compound 5-hydroxy-7,4'-dimethoxyflavone may be partly responsible for the reported antifungal activity of C. zeyheri, and may serve as a potential source of lead compounds that can be developed as antifungal phytomedicines.
Topics: Antifungal Agents; Antioxidants; Apigenin; Candida albicans; Chromatography, Thin Layer; Combretum; Microbial Sensitivity Tests; Plant Extracts; Plant Leaves
PubMed: 26573005
DOI: 10.1186/s12906-015-0934-7 -
PeerJ 2022(FOC4) is a pathogen of banana fusarium wilt, which is a serious problem that has plagued the tropical banana industry for many years. The pathogenic mechanism is...
(FOC4) is a pathogen of banana fusarium wilt, which is a serious problem that has plagued the tropical banana industry for many years. The pathogenic mechanism is complex and unclear, so the prevention and control in agricultural production applications is ineffective. SNP-D4, an artificial peptide aptamer, was identified and specifically inhibited FOC4. To evaluate the efficacy of SNP-D4, FoC4 spores were treated with purified SNP-D4 to calculate the germination and fungicide rates. Damage of FOC4 spores was observed by staining with propidium iodide (PI). Eight proteins of FOC4 were identified to have high affinity for SNP-D4 by a pull-down method combined with Q-Exactive mass spectrometry. Of these eight proteins, A0A5C6SPC6, the aldehyde dehydrogenase of FOC4, was selected as an example to scrutinize the interaction sites with SNP-D4. Molecular docking revealed that Thr66 on the peptide loop of SNP-D4 bound with Tyr437 near the catalytic center of A0A5C6SPC6. Subsequently 42 spore proteins which exhibited associations with the eight proteins were retrieved for protein-protein interaction analysis, demonstrating that SNP-D4 interfered with pathways including 'translation', 'folding, sorting and degradation', 'transcription', 'signal transduction' and 'cell growth and death', eventually causing the inhibition of growth of FOC4. This study not only investigated the possible pathogenic mechanism of FOC4, but also provided a potential antifungal agent SNP-D4 for use in the control of banana wilt disease.
Topics: Fusarium; Antifungal Agents; Aptamers, Peptide; Molecular Docking Simulation; Oligonucleotides; Peptides; Musa
PubMed: 35223198
DOI: 10.7717/peerj.12756 -
Antimicrobial Agents and Chemotherapy Jun 2020, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species....
, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the section However, little is yet known among the section about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The MICs of itraconazole, voriconazole, posaconazole, isavuconazole, and amphotericin B were determined by both the EUCAST and gradient concentration strip methods. ( = 51, 45.5%) and ( = 50, 44.6%) were the most common species while accounted for only 6.3% ( = 7). The MICs of azole drugs were higher for than for The MIC of amphotericin B was 2 mg/liter or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by the gradient concentration strip method, with the latter being lower than the former (Spearman's rank correlation tests ranging from 0.01 to 0.25 depending on the antifungal agent; > 0.4). In conclusion, should be considered as a minority species in the section The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and the gradient concentration strip methods require further investigation.
Topics: Antifungal Agents; Aspergillus; France; Itraconazole; Microbial Sensitivity Tests
PubMed: 32312779
DOI: 10.1128/AAC.02510-19 -
The Journal of Dermatology Oct 2018Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study.
Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F-RVCZ, compared with a placebo, were investigated in a multicenter, double-blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F-RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end-point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36-week post-treatment visit). Secondary end-points were changes over time in the efficacy and mycological effect of F-RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F-RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F-RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F-RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F-RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.
Topics: Adult; Aged; Antifungal Agents; Double-Blind Method; Female; Foot Dermatoses; Humans; Male; Middle Aged; Onychomycosis; Prodrugs; Thiazoles; Treatment Outcome; Triazoles; Young Adult
PubMed: 30156314
DOI: 10.1111/1346-8138.14607 -
Antimicrobial Agents and Chemotherapy May 2021antifungal susceptibility profiling of 32 clinical and environmental isolates recovered from southern China was performed against olorofim and 7 other systemic...
antifungal susceptibility profiling of 32 clinical and environmental isolates recovered from southern China was performed against olorofim and 7 other systemic antifungals, including amphotericin B, 5-flucytosine, posaconazole, voriconazole, caspofungin, and terbinafine, using CLSI methodology. In comparison, olorofim was the most active antifungal agent against both mold and yeast phases of all tested isolates, exhibiting an MIC range, MIC, and MIC of 0.0005 to 0.002 μg/ml, 0.0005 μg/ml, and 0.0005 μg/ml, respectively.
Topics: Acetamides; Antifungal Agents; China; Microbial Sensitivity Tests; Piperazines; Pyrimidines; Pyrroles; Saccharomyces cerevisiae; Talaromyces; Voriconazole
PubMed: 33753341
DOI: 10.1128/AAC.00256-21 -
International Journal of Nanomedicine 2021Fungal keratitis (FK) remains a severe sight-threatening disease, and case management is difficult due to ocular intrinsic barriers and drug shortages. Econazole (ECZ),...
INTRODUCTION
Fungal keratitis (FK) remains a severe sight-threatening disease, and case management is difficult due to ocular intrinsic barriers and drug shortages. Econazole (ECZ), a broad-spectrum antifungal agent, is limited in ocular applications due to the poor water solubility and strong irritant property.
METHODS
We successfully prepared solid-lipid nanoparticle-based ECZ eye drops (E-SLNs) by microemulsion method, and the physicochemical properties of E-SLNs were investigated. Corneal permeability, antifungal ability against spp., irritation and bioavailability compared to ECZ Suspension (E-Susp) were evaluated in vitro and in vivo.
RESULTS
E-SLNs were a uniform and stable system which had an average particle size of 19 nm and a spherical morphology. E-SLNs also exhibited controlled release, enhanced antifungal activity without irritation. The pharmacokinetic analysis in vivo confirmed that E-SLNs showed an improved ocular bioavailability and the drug concentration in the cornea were above minimum inhibitory concentration (MIC) for 3 h after single administration.
CONCLUSION
The E-SLNs colloid system is a promising therapeutic approach for fungal keratitis and could serve as a candidate strategy for other ocular diseases.
Topics: Animals; Antifungal Agents; Cornea; Drug Carriers; Lipids; Liposomes; Nanoparticles; Particle Size; Rabbits
PubMed: 34876813
DOI: 10.2147/IJN.S340068 -
Revista Espanola de Quimioterapia :... Sep 2017We sought to review the most important updates in the treatment of aspergillosis after the publication of the clinical practice guidelines for the diagnosis and... (Review)
Review
We sought to review the most important updates in the treatment of aspergillosis after the publication of the clinical practice guidelines for the diagnosis and management of invasive aspergillosis (IA) by the Infectious Diseases Society of America. Our aim is to discuss some of the key aspects concerning the following topics: early initiation of antifungal therapy, antifungal agent of choice, follow-up of patients with IA, and breakthrough aspergillosis.
Topics: Antifungal Agents; Aspergillosis; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Mycology; Practice Guidelines as Topic
PubMed: 28882011
DOI: No ID Found -
Yakugaku Zasshi : Journal of the... 2018The emergence of antimicrobial resistant (AMR) bacteria has become a serious threat to public health. It is important that we find a mechanistically novel antibiotic... (Review)
Review
The emergence of antimicrobial resistant (AMR) bacteria has become a serious threat to public health. It is important that we find a mechanistically novel antibiotic to combat AMR. However, finding compounds which are both therapeutically effective and safe is difficult in the development of antibiotics. To solve these problems, we have focused on the silkworm model, which is economical and poses fewer ethical issues, as a means to evaluate the therapeutic effectiveness of test compounds in early stages of antibiotic development. Actually, the silkworm has pharmacokinetic parameters similar to mammals, and we revealed that antibiotics showed EDs consistent with mammalian models. Thus, we screened therapeutically effective samples from natural products using the silkworm model, and found 23 candidates out of 15000 samples. We ultimately identified a novel antibiotic, lysocin E, and found that it demonstrates a potent therapeutic effect in the mouse systemic infection model. Furthermore, since the target of lysocin E is menaquinone on the bacterial membrane, it belongs to a novel class of antibiotics. In addition, we found a novel antibacterial agent named nosokomycin, GPI0363, and an antifungal agent, VL-2397 (ASP2397), using the silkworm model. In this report, we introduce the usefulness of the silkworm model in the development of antibiotics.
Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bombyx; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery; Drug Evaluation, Preclinical; Mice; Peptides, Cyclic
PubMed: 29962465
DOI: 10.1248/yakushi.17-00202-4