MOLECULES
·
2023
·Vol. 28
·期 12
·4722
·
IF 4.6
Tao Wang,Qiuxiao Wang,Yifei Zhou,Yaolin Shi,Haixiang Gao
Terbinafine, an inhibitor of squalene epoxidase in ergosterol biosynthesis, is chiefly utilized as an antifungal medication with potential uses in pesticide applications. This study explores the fungicidal efficacy of terbinafine against prevalent plant pathogens and confirms its effectiveness. To augment its water solubility, five ionic salts of terbinafine were synthesized by pairing them with organic acids. Among these salts, TIS 5 delivered the most impressive results, amplifying the water solubility of terbinafine by three orders of magnitude and lessening its surface tension to facilitate better dispersion during spraying. The in vivo experiments on cherry tomatoes showed that TIS 5 had a superior therapeutic activity compared to its parent compound and two commonly used broad-spectrum fungicides, pyraclostrobin and carbendazim. The results highlight the potential of terbinafine and its ionic salts, particularly TIS 5, for use as fungicides in agriculture due to their synergistic effects with furan-2-carboxylate.Keywords:terbinafine;ionic salts;solubility;surface tension;agricultural antifungal activity
研究领域:
农业科学
·
药理学
·
植物病理学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2015
·
IF 2.558
Yan Yang,Rujing Ou,Shixia Guan,Xiaoling Ye,Bo Hu,Yi Zhang,Shufan Lu,Yubin Zhou,Zhongwen Yuan,Jun Zhang,Qing-guo Li
Context: Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis.Objective: This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability.Materials and methods: Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine.Results: Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm−2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm–2. The results of pharmacokinetic studies showed the Cmax and area under the curve (AUC) were apparently higher than the commercial cream.Discussion and conclusion: The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.
研究领域:
药剂学
·
皮肤病学
·
生物医学工程
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DOI
PubMed
高影响因子
Gels
·
2024
·Vol. 10
·期 7
·456
·
IF 5
Mengfei Li,Xinghao Chen,Xiangxiang Su,Wenyan Gao
Background:Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers.Methods:The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch’s permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity.Results:The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0–8 h)was 3.4 and 5.4 times higher, while the Cmaxwas 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells.Conclusions:This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections.
研究领域:
药剂学
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药物递送系统
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药理学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Feng Feng,Xing Ge,Tianye Fang,Kaiyang Chen,Jiaying Zhu,Jun Yang,Lei Tao,Jianjun Dai,Yanmin Ju
Dermatophytosis is a complex and prevalent fungal skin infection that affects a significant portion of the global population. Conventional antifungal therapies are often compromised by their inability to effectively penetrate fungal biofilms and limited skin permeability, ultimately leading to unsatisfactory clinical results. To address these issues, we proposed a novel dissolvable microneedle (MN) patch (denoted as TB/QCS MNs) that encapsulated terbinafine (TB) within the quaternary ammonium chitosan (QCS) MN tips. The combination of QCS and TB exhibited a pronounced synergistic effect against Trichophyton mentagrophytes (T. mentagrophytes). Importantly, TB/QCS MNs effectively disrupted fungal biofilms and damaged extracellular polymeric substances. In comparison to TB alone, TB/QCS MNs effectively accelerated fungal clearance, shortened treatment time, and enhanced skin recovery in T. mentagrophytes-infected C57BL/6 mice. These findings demonstrated that TB/QCS MNs significantly improve therapeutic efficacy for dermatophytosis, offering a promising alternative for clinical treatment of skin fungal infections.
研究领域:
药剂学
·
真菌学
·
生物医学工程
·
皮肤科学
·
高分子科学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Hao Yan,Xiangliang Huang,Yourong Zhou,Yuan Mu,Shaoyin Zhang,Yashi Cao,Wentong Wu,Zhifei Xu,Xueqin Chen,Xiaochen Zhang,Xiaohong Wang,Xiaochun Yang,Bo Yang,Qiaojun He,Peihua Luo
Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified. In this study, a single regulatory mechanism of small molecule kinase inhibitors, with crizotinib as the representative drug is elucidated. First, it is discovered that crizotinib induced aberrant lipid metabolism and apoptosis in the liver. A mechanistic study revealed that crizotinib treatment promoted the accumulation of squalene epoxidase (SQLE) by inhibiting autophagosome-lysosome fusion which blocked the autophagic degradation of SQLE. A maladaptive increase in SQLE led to disturbances in cholesterol and sphingolipid metabolism via an enzymatic activity-dependent manner. Abnormal cholesterol results in both steatosis and inflammatory infiltration, and disturbances in sphingolipid metabolism promote cell apoptosis by inducing lysosomal membrane permeabilization. The restoration of the level or activity of SQLE ameliorated steatosis and hepatocyte injury. The autophagy activator known as metformin or the SQLE enzymatic inhibitor known as terbinafine has potential clinical use for alleviating crizotinib hepatotoxicity.
研究领域:
药理学
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肝病学
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分子生物学
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药物毒理学
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产品关联
DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2024
·
IF 9.7
Tian-Qiong Shi,Yi-hang Shen,Ya-Wen Li,Zi-Yi Huang,Zhi-Kui Nie,Chao Ye,Yue-Tong Wang,Qi Guo
Gibberellic acid (GA3), produced industrially by Fusarium fujikuroi , stands as a crucial plant growth regulator extensively employed in the agriculture filed while limited understanding of the global metabolic network hinders researchers from conducting rapid targeted modifications. In this study, a small-molecule compounds-based targeting technology was developed to increase GA3 production. Firstly, various small molecules were used to target key nodes of different pathways and the result displayed that supplement of terbinafine improved significantly GA3 accumulation, which reached to 1.08 g/L. Subsequently, lipid and squalene biosynthesis pathway were identified as the key pathways influencing GA3 biosynthesis by transcriptomic analysis. Thus, the strategies including in vivo metabolic engineering modification and in vitro supplementation of lipid substrates were adopted, both contributed to an enhanced GA3 yield. Finally, the engineered strain demonstrated the ability to achieve a GA3 yield of 3.24 g/L in 5 L bioreactor when utilizing WCO as carbon source and feed.
研究领域:
植物科学
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分子生物学
·
生物技术
·
代谢工程
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产品关联
DOI
PubMed
高影响因子
MYCOSES
·
2018
·Vol. 62
·期 5
·466-474
·
IF 2.793
Yangmin Gao,Ping Zhan,Ferry Hagen,Steph B. J. Menken,Jiufeng Sun,Ali Rezaei-Matehkolaei,Sybren de Hoog
Summary Trichophyton schoenleinii is an anthropophilic dermatophyte usually causing tinea favosa. Only few studies have provided data on molecular epidemiology and antifungal profiles of this fungus due to its limited prevalence after 1950s. Forty-nine strains from Asia (n = 27), Africa (n = 10), Europe (n = 10) and from unknown regions (n = 2) were analysed with amplified fragment length polymorphism fingerprinting (AFLP) to reveal intraspecific genetic diversity in this dataset. Amplified fragment length polymorphism fingerprinting genotyping revealed five clusters which did not correspond to geographic origins or clinical characteristics. Additionally, in vitro antifungal susceptibility to seven antifungals was provided for all strains. Terbinafine, ketoconazole, miconazole and itraconazole proved to be the most effective drugs, followed by griseofulvin. No correlation between genotypes and differences in antifungal susceptibility was observed. It is concluded that the AFLP groups are lineages within a single species.
研究领域:
医学真菌学
·
流行病学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2023
·
IF 2.6
Xiaotong Yang,Jidong Wang,Miao Ma,Dongxu Wang,Jinliang Wu,Zhong Zhao
In this paper, the solubility of terbinafine hydrochloride in 13 mono-solvents was measured in the temperature range from 283.15 K to 323.15 K at ambient pressure with the assistance of a laser-based dynamic solubility-monitoring device. It was concluded that the solubility of terbinafine hydrochloride in these mono-solvents increases with rising temperature. At 323.15 K, the molar solubility shows the following order: cyclohexanol (7.739 × 10–2) > n-propyl alcohol (7.351 × 10–2) > n-amyl alcohol (6.967 × 10–2) > iso-butanol (6.932 × 10–2) > n-butanol (6.850 × 10–2) ≈ ethanol (6.778 × 10–2) > isoamyl alcohol (4.926 × 10–2) >1-hexanol (4.689 × 10–2) > dimethyl sulfoxide (4.010 × 10–2) > sec-butanol (2.878 × 10–2) > isopropyl alcohol (2.452 × 10–2) > isooctyl alcohol (2.211 × 10–2) > acetonitrile (0.532 × 10–2). Subsequently, the relationship between the solubility of terbinafine hydrochloride and temperature was correlated by six models (Apelblat, van’t Hoff, λh, Wilson, NRTL, and Jouyban models), and the mixing thermodynamic properties of the solutions were evaluated with the solubility and the parameters simulated by the Wilson model. In addition, the solvent effect on the solubility of terbinafine hydrochloride was discussed based on the Kamlet–Abboud–Taft linear solvation energy relationships.
研究领域:
药物化学
·
物理化学
·
热力学
·
溶剂化科学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Peng Min,Zhang Chen,Duan Yuan-Yuan,Liu Hai-Bo,Peng Xin-Yuan,Wei Qian,Chen Qi-Ying,Sang Hong,Kong Qing-Tao
Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.
研究领域:
药理学
·
微生物学
·
传染病学
·
真菌学
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产品关联
DOI
PubMed
高影响因子
Virulence
·
2026
·
IF 6.8
Ya-Hong Wang,Die Zhu,Dan Wang,Ruo-Cheng Sheng,Li-Chao Wang,Chen-Ning Zhang,Muhammad Faizan Latif,Huan Li,Feng-Mao Chen
The normal polar growth and morphogenesis represent fundamental factors in development, reproduction survival and host invasion of phytopathogenic fungi. The heterotetramerized AP-2 complex is widely present in eukaryotes and plays a specific role in clathrin-mediated vesicle formation and transport at the plasma membrane in mammals and plants. However, the functions of AP-2 complex in growth, metabolism and virulence of plant pathogenic fungi remain unclear. In this study, the conserved VdAP-2α subunit was identified in Verticillium dahliae by screening of a T-DNA insertion library. VdAP-2α was significantly induced during the developmental phases of V. dahliae, and its GFP-fused signals exhibited a punctate distribution in cytoplasm and on the plasma membrane. Like the insertional mutant, the deletion of VdAP-2α caused the suppression of radial growth, conidiation and virulence, as well as aggravated formation of melanized microsclerotia. Comparative transcriptomic analysis further elucidated the global regulation of VdAP-2α, including hyphal growth, vesicle transport, redox reactions and metabolic processes. Moreover, the impairment of hyphal polarity disordered chitin distribution, bidirectional conidia germination and hydrophobicity, which were associated with membrane defects caused by the decreasing of membrane-associated ergosterols and intermediates. These results contribute to the understanding of the functional characteristics of the AP-2 complex in filamentous fungi and suggest potential antifungal targets.
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Li Wanqian,Whiteway Malcolm,Hang Sijin,Yu Jinhua,Lu Hui,Jiang Yuanying
Azole effectiveness against candidiasis can be compromised by Candida albicans resistance and tolerance, and unfortunately, few clinically useful compounds can enhance azole antifungal activities. We find that the amino acids V234, F235 and L238 of Erg11 are critical for its interaction with Ncp1, and the Ncp1-Erg11 association is important in azole response. Ellipticine and its analog phiKan 083 block this Erg11-Ncp1 interaction by targeting Ncp1, and boost antifungal effects of fluconazole in vitro and in vivo. A series of steps influencing this process—an initial elevation in reactive oxygen species, leading to protein oxidation and misfolding in the endoplasmic reticulum (ER) that causes ER stress. This stress leads to Ca 2+ release from the ER, mitochondrial Ca 2+ accumulation and dysfunction, increased ROS production, and apoptosis of C. albicans cells. Overall, disrupting the Erg11-Ncp1 interaction in C. albicans can serve as a useful approach to enhancing the antifungal properties of azoles.
研究领域:
微生物学
·
分子生物学
·
药理学
·
生物化学
·
医学真菌学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Meng Wang,Yanwen Zhou,Zhaohui Wang
The critical shortage of antifungal drugs and increasingly emerged resistant fungi urgently call for the development of novel fungicidal agents with translational potential. Although nanodrugs compose a new antifungal arsenal, the fungicidal efficacy barely exceeds clinical molecules. In this study, a CuFeSe 2 -PVP nano-blade, is unexpectedly discovered with ultrapotent intrinsic fungicidal efficacy. This nanostructure is facilely fabricated by a specific aqueous precipitation method with the nucleation of tetragonal eskebornite CuFeSe 2 at PVP chains. The unique semiconductor CuFeSe 2 -PVP demonstrates superior antifungal activity than the commonly used small-molecule drugs and metal nanoparticles in both planktonic fungi and biofilm. Intriguingly, electron microscopy visualizes that the nano-blades cut fungal membranes with fungi surfaces inserted by the blades. Such a membrane-piercing effect results in the loss of important intracellular components, including nucleic acids , proteins, and potassium ions. Increased intracellular reactive oxygen species (ROS) is also observed. Encouragingly, in mice with subcutaneous fungal infection, the nanodrug achieves absolute fungi clearance, effectively alleviating inflammation and promoting collagen fiber recovery. Moreover, the excellent biocompatibility of CuFeSe 2 -PVP promises great potential for further translation. This study not only provides a novel fungicidal drug candidate, but also inspires the future design of anti-fungal nanomedicine .
研究领域:
纳米技术
·
药学
·
微生物学
·
材料科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）