34 results on '"Xin Wang"'
Search Results
2. Ethylenediaminetetraacetic Acid Disodium Salt Acts as an Antifungal Candidate Molecule against Fusarium graminearum by Inhibiting DON Biosynthesis and Chitin Synthase Activity
- Author
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Kai-Xin Gu, Xiu-Shi Song, Shao-Chen Ding, Jian-Xin Wang, Mingguo Zhou, and Jing Gao
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Fusarium ,chitin synthases ,Antifungal Agents ,Health, Toxicology and Mutagenesis ,deoxynivalenol ,lcsh:Medicine ,Ethylenediaminetetraacetic acid ,Toxicology ,Article ,Microbiology ,Cell wall ,03 medical and health sciences ,chemistry.chemical_compound ,Chitin ,Biosynthesis ,Gene Expression Regulation, Fungal ,Magnesium ,Mycotoxin ,Edetic Acid ,030304 developmental biology ,Calcium Chelating Agents ,chemistry.chemical_classification ,Chitin Synthase ,0303 health sciences ,Manganese ,EDTANa2 ,biology ,030306 microbiology ,lcsh:R ,food and beverages ,biology.organism_classification ,Fungicide ,Enzyme ,chemistry ,manganese ion ,Calcium ,Trichothecenes - Abstract
Fusarium fungi are the cause of an array of devastating diseases affecting yield losses and accumulating mycotoxins. Fungicides can be exploited against Fusarium and deoxynivalenol (DON) production. However, Fusarium resistance to common chemicals has become a therapeutic challenge worldwide, which indicates that new control agents carrying different mechanisms of action are desperately needed. Here, we found that a nonantibiotic drug, ethylenediaminetetraacetic acid disodium salt (EDTANa2), exhibited various antifungal activities against Fusarium species and DON biosynthesis. The infection of wheat seeding caused by F. graminearum was suppressed over 90% at 4 mM EDTANa2. A similar control effect was observed in field tests. Mycotoxin production assays showed DON production was significantly inhibited, 47% lower than the control, by 0.4 mM EDTANa2. In vitro experiments revealed a timely inhibition of H2O2 production as quickly as 4 h after amending cultures with EDTANa2 and the expression of several TRI genes significantly decreased. Chitin synthases of Fusarium were Mn2+-containing enzymes that were strongly inhibited by Mn2+ deficiency. EDTANa2 inhibited chitin synthesis and destroyed the cell wall and cytomembrane integrity of Fusarium, mainly via the chelation of Mn2+ by EDTANa2, and thus led to Mn deficiency in Fusarium cells. Taken together, these findings uncover the potential of EDTANa2 as a fungicide candidate to manage Fusarium head blight (FHB) and DON in agricultural production.
- Published
- 2021
3. Discovery of novel selenium-containing azole derivatives as antifungal agents by exploiting the hydrophobic cleft of CYP51
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Hang Xu, Yan-hua Mou, Meng-bi Guo, Rui Zhang, Zhong-zuo Yan, Ran An, Xin Wang, Xin Su, Zhuang Hou, and Chun Guo
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Pharmacology ,Azoles ,Mice ,Selenium ,Structure-Activity Relationship ,Antifungal Agents ,Organic Chemistry ,Drug Discovery ,Candida albicans ,Animals ,General Medicine ,Microbial Sensitivity Tests ,Fluconazole - Abstract
Herein, we report the design, synthesis and evaluation of a novel series of diselenide and selenide derivatives as potent antifungal agents by exploiting the hydrophobic cleft of CYP51. Among all synthesized compounds, the most potent compound B01 with low cytotoxic and hemolysis effect exhibited excellent activity against C.alb., C.gla., C.par. and C.kru., as well as selected fluconazole-resistant strains. Moreover, compound B01 could reduce the biofilm formation of the FCZ-resistant C.alb. Subsequently, metabolic stability assays using liver microsomes demonstrated that compound B01 showed good profiles of metabolic stability. With superior pharmacological profile, compound B01 was advanced into in vivo bioactivity evaluation. In a murine model of systemic C.alb. infection, compound B01 significantly reduced fungal load of kidneys. Furthermore, compound B01 revealed relatively low acute toxicity and subacute toxicity in mice. In addition, docking study performed into C.alb. CYP51, showed the binding mode between C.alb. CYP51 and compound B01. Collectively, diselenides compound B01 can be further developed for the potential treatment of invasive fungal infections.
- Published
- 2021
4. Complete genome sequence of Bacillus velezensis WB, an isolate from the watermelon rhizosphere: genomic insights into its antifungal effects
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Ke-Xin Wang, Wei-Hui Xu, Zhong-Nan Chen, Jia-Le Hu, Shi-Qi Luo, and Zhi-Gang Wang
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Microbiology (medical) ,Citrullus ,Antifungal Agents ,Immunology ,Rhizosphere ,Immunology and Allergy ,Bacillus ,Genomics ,Microbiology - Abstract
Here, we report the complete genome of strain WB, isolated from the rhizosphere of a healthy watermelon from a Fusarium wilt diseased field, which possesses antifungal activity against Fusarium oxysporum f. sp. niveum (Fon) and reduces the incidence of Fusarium wilt in watermelon.Genome sequences were determined using the Illumina HiSeq and PacBio platforms. Genome assembly was performed by Unicycler software. Gene clusters responsible for secondary metabolite biosynthesis were predicted using antiSMASH.The size of the genome was 3 896 799 base pairs, and there were 3977 coding DNA sequences (CDSs). The G+C content of the circular genome was 46.65%, and there were 27 rRNAs and 86 tRNAs. Strain WB was finally designated Bacillus velezensis based on phylogenomic analyses. In addition, 13 gene clusters were related to the synthesis of antimicrobial secondary metabolites, including surfactin, fengycin, iturin, bacillibactin, bacilysin, bacillaene, and butirosin.The complete genome sequence of strain WB reported here will be a valuable reference for studying the biocontrol mechanisms of Fusarium wilt in watermelon.
- Published
- 2021
5. Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models.
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Xiao-Jun Cai, Rui-Dong Li, Jian-Hua Li, Yi-Feng Tao, Quan-Bao Zhang, Cong-Huan Shen, Xiao-Fei Zhang, Zheng-Xin Wang, and Zheng Jiao
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LIVER transplantation ,TACROLIMUS ,ANTIFUNGAL agents ,MONTE Carlo method ,PHARMACOKINETICS ,DRUG metabolism - Abstract
Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms. Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis--Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens. Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h
-1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (Vmax ) of the nonlinear MM model was 6.62 mg day-1 ; the average concentration at steady state at half-Vmax (Km) was 6.46 ng ml-1 . The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations. Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation. [ABSTRACT FROM AUTHOR]- Published
- 2022
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6. Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect
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Zhehao Zhang, Jingyu Zhu, Xin Yang, Mengyao Fan, Yi Qian, Zejun Pei, Kaiyuan Deng, Zaixiang Lou, Xin Wang, and Xin Sun
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Virtual screening ,Antifungal Agents ,Serine C-Palmitoyltransferase ,Computational biology ,RM1-950 ,SPT ,01 natural sciences ,chemistry.chemical_compound ,Mice ,Docking (dog) ,Biosynthesis ,Drug Discovery ,Animals ,Humans ,Enzyme Inhibitors ,Pharmacology ,010405 organic chemistry ,Chemistry ,Brief Report ,Serine C-palmitoyltransferase ,General Medicine ,Sphingolipid ,0104 chemical sciences ,Molecular Docking Simulation ,inhibitor ,010404 medicinal & biomolecular chemistry ,anti-fungi ,Identification (biology) ,Therapeutics. Pharmacology - Abstract
Serine palmitoyltransferase (SPT) plays the key role on catalysing the formation of 3-ketodihydrosphingosine, which is the first step of the de novo biosynthesis of sphingolipids. SPT is linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, a logical docking-based virtual screening method was used to screen selective SPT inhibitor against fungi, not human. We used myriocin-similarity database to identify compounds with good binding with fungal SPT and poor binding with homology human SPT model. Preliminary bio-assay led to the discovery of a promising inhibitor WXP-003, which displayed good inhibitory activity against diversity fungi strains with MIC ranging from 0.78 to 12.5 μg/mL. WXP-003 could significantly reduce sphingolipids content in fungi and no effect on mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed the favoured interactions. Taken together, discovery of WXP-003 provided valuable guide for the development of novel anti-fungal agents.
- Published
- 2021
7. Functional dissection of individual domains in group III histidine kinase Sshk1p from the phytopathogenic fungus Sclerotinia sclerotiorum
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Qiao Wang, Yabing Duan, Tao Li, Qian Xiu, Jian-Xin Wang, and Mingguo Zhou
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0106 biological sciences ,0301 basic medicine ,Antifungal Agents ,biology ,Histidine Kinase ,Chemistry ,Health, Toxicology and Mutagenesis ,Dissection ,Histidine kinase ,Mutant ,Sclerotinia sclerotiorum ,General Medicine ,Fludioxonil ,biology.organism_classification ,01 natural sciences ,010602 entomology ,03 medical and health sciences ,030104 developmental biology ,Protein kinase domain ,Biochemistry ,Ascomycota ,Phosphorylation ,Agronomy and Crop Science ,Function (biology) ,Intracellular - Abstract
A conserved kinase domain and phosphoryl group receiver domain at the C-terminus and poly-HAMP domains at the N-terminus comprise the structural components of the group III HK which was considered as a potential antifungal target. However, the roles of individual domains in the function of group III HKs have rarely been dissected in fungi. In this study, we dissected the roles of individual domains to better understand the function of Sshk1p, a group III HK from Sclerotinia sclerotiorum. The results suggest that individual domains play different roles in the functionality of Sshk1p and are implicated in the regulation of mycelial growth, sclerotia formation, pathogenicity. And the mutants of each domain in Sshk1 showed significantly increased sensitivity to hyperosmotic stress. However, the mutants of each domain in Sshk1 showed high resistance to fludioxonil and dimethachlon which suggested that all nine domains of Sshk1p were indispensable for susceptibility to fludioxonil and dimethachlon. Moreover, deletion of each individual domain in Sshk1 cancelled intracellular glycerol accumulation and increased SsHog1p phosphorylation level triggered by NaCl and fludioxonil, suggesting that all the domains of Sshk1 were essential for Sshk1-mediated SsHog1p phosphorylation and subsequent polyol accumulation in response to fludioxonil and hyperosmotic stress.
- Published
- 2021
8. Appropriate Source Control and Antifungal Therapy are Associated with Improved Survival in Critically Ill Surgical Patients with Intra-abdominal Candidiasis
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Ting Yan, Dong-Xin Wang, Sai-Nan Zhu, Lei Huang, Hai-Li Ou, and Shuang-Ling Li
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Adult ,Male ,medicine.medical_specialty ,Abdominal Abscess ,Antifungal Agents ,Critical Care ,Critical Illness ,Peritonitis ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Risk Factors ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Surgical Wound Infection ,030212 general & internal medicine ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,0303 health sciences ,030306 microbiology ,Septic shock ,business.industry ,Proportional hazards model ,Candidiasis ,Vascular surgery ,Middle Aged ,medicine.disease ,Intensive care unit ,Combined Modality Therapy ,Survival Rate ,Intensive Care Units ,Treatment Outcome ,Cardiothoracic surgery ,Surgery ,Female ,business ,Abdominal surgery ,Cohort study ,Follow-Up Studies - Abstract
BackgroundIntra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in surgical intensive care patients. The purpose of this study was to investigate the impact of appropriate source control and antifungal therapy on the outcomes of critically ill surgical patients with IAC.MethodsThis was a retrospective single-center cohort study. Adult surgical patients who were admitted to the intensive care unit and diagnosed with IAC from January 1, 2003, to December 31, 2016, were enrolled. The patients’ data including risk factors of IAC, infection-related information, antifungal treatment and 30-day outcomes were collected. The primary endpoint was 30-day mortality. A COX proportional hazards model was used to analyze the association between appropriate treatment and 30-day survival.ResultsA total of 82 patients were included in the analysis. Of these, 45 (54.9%) were complicated with septic shock at IAC diagnosis. Types of IAC included peritonitis (61.0%), intra-abdominal abscesses (23.2%) and biliary tract infections (15.9%). Of the included patients, 53 (64.6%) received appropriate source control and 44 (53.7%) appropriate antifungal therapy. Compared with patients with neither of these treatments, appropriate source control (HR 0.08, 95% CI 0.02–0.30;P P = 0.005), and a combination of these treatments (HR 0.02, 95% CI 0.00–0.08;P ConclusionFor critically ill surgical patients with IAC, both appropriate source control and appropriate antifungal therapy were associated with reduced risk of 30-day mortality, and the protective effects of the two appropriate treatments were additive.
- Published
- 2020
9. Discovery of 1,2,3-selenadiazole analogues as antifungal agents using a scaffold hopping approach
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Hang Xu, Yanhua Mou, Xin Wang, Ran An, Zhuang Hou, Chun Cao, Rui Zhang, Chun Guo, Zhong-zuo Yan, En-hui Dong, and Meng-bi Guo
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Azoles ,Models, Molecular ,Antifungal ,Antifungal Agents ,medicine.drug_class ,Scaffold hopping ,Biochemistry ,chemistry.chemical_compound ,Organoselenium Compounds ,Candida albicans ,Drug Discovery ,medicine ,Humans ,Cytotoxicity ,Molecular Biology ,chemistry.chemical_classification ,Lanosterol ,Organic Chemistry ,Candidiasis ,Biofilm ,Corpus albicans ,Fungicide ,Enzyme ,chemistry ,Biofilms ,Drug Design - Abstract
With the increasing incidence of antifungal resistance, new antifungal agents having novel scaffolds hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. In this study, we reported the design, synthesis, and pharmacological evaluation of novel 1,2,3-selenadiazole analogues by scaffold hopping strategy. Preliminary results of antifungal activity demonstrated that the new class of compounds showed broad-spectrum fungistatic and fungicidal activity. Most importantly, these newly synthesized compounds can eliminate these azole-resistant fungi and inhibit the formation of C. albicans biofilm. In particular, compound S07 showed promising antifungal activity against five azole-resistant strains with MIC values ranging from 4 to 32 μg/mL. Then, further target identification and mechanistic studies indicated that representative compound S07 exert its inhibitory activity by inhibiting fungal lanosterol 14α-demethylase enzyme (CYP51). Interestingly, representative compounds showed low cytotoxicity on mammalian cell lines. In addition, the molecular docking studies elucidated the binding modes of these compounds toward CYP51. Altogether, these results suggest that compound S07 with novel skeleton is a promising CYP51 inhibitor for treatment of fungal infections.
- Published
- 2021
10. Azole-triphenylphosphonium conjugates combat antifungal resistance and alleviate the development of drug-resistance
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Ming Zhang, Jinyao Chen, Liu Jun, Wenqiang Chang, Xin Wang, Gang Li, Chuan Tian, Xiao-Ping Peng, and Hong-Xiang Lou
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Antifungal Agents ,Cell Survival ,Drug resistance ,Pharmacology ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Organophosphorus Compounds ,Biosynthesis ,Drug Resistance, Fungal ,Drug Discovery ,medicine ,Humans ,Cytotoxicity ,Molecular Biology ,Candida ,chemistry.chemical_classification ,Ergosterol ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,Biofilm ,Corpus albicans ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,A549 Cells ,Biofilms ,PC-3 Cells ,Azole ,Fluconazole ,medicine.drug - Abstract
Azole antifungals are commonly used to treat fungal infections but have resulted in the occurrence of drug resistance. Therefore, developing azole derivatives (AZDs) that can both combat established drug-resistant fungal strains and evade drug resistance is of great importance. In this study, we synthesized a series of AZDs with a fluconazole (FLC) skeleton conjugated with a mitochondria-targeting triphenylphosphonium cation (TPP+). These AZDs displayed potent activity against both azole-sensitive and azole-resistant Candida strains without eliciting obvious resistance. Moreover, two representative AZDs, 20 and 25, exerted synergistic antifungal activity with Hsp90 inhibitors against C. albicans strains resistant to the combination treatment of FLC and Hsp90 inhibitors. AZD 25, which had minimal cytotoxicity, was effective in preventing C. albicans biofilm formation. Mechanistic investigation revealed that AZD 25 inhibited the biosynthesis of the fungal membrane component ergosterol and interfered with mitochondrial function. Our findings provide an alternative approach to address fungal resistance problems.
- Published
- 2021
11. Rare Fungal Keratitis Caused by Coprinellus Radians
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Li Zhang, Xin Wang, Xiaofeng Li, Xiaolin Qi, and Xiuhai Lu
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0301 basic medicine ,Posaconazole ,Coprinellus radians ,Antifungal Agents ,Itraconazole ,Veterinary (miscellaneous) ,030106 microbiology ,Hyphae ,Fungus ,Microbial Sensitivity Tests ,Biology ,Applied Microbiology and Biotechnology ,Microbiology ,Corneal Transplantation ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Amphotericin B ,DNA, Ribosomal Spacer ,medicine ,Humans ,Fungal keratitis ,Corneal Ulcer ,DNA, Fungal ,Voriconazole ,Keratitis ,Middle Aged ,Triazoles ,medicine.disease ,biology.organism_classification ,Female ,Agaricales ,Agronomy and Crop Science ,Eye Infections, Fungal ,Fluconazole ,medicine.drug - Abstract
A case of fungal keratitis due to Coprinellus radians is reported. To our knowledge, fungal keratitis caused by this species was rare. Fungal hyphae were detected in corneal scrapings, and isolates were identified by morphology and by sequencing the internal transcribed spacer region of ribosomal DNA. The patient was treated with systemic and local antifungal therapy for 5 days, and lamellar keratoplasty was performed after no obvious improvement in symptoms. The in vitro antifungal susceptibilities of the case strain were tested for six antifungal agents. The results showed that 5-fluorouracil was resistant, fluconazole was moderately sensitive, and the other drugs assayed (amphotericin B, posaconazole, itraconazole and voriconazole) were highly effective against this fungus.
- Published
- 2019
12. Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections
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Ran An, Zhong-zuo Yan, Chun Guo, Hang Xu, Xin Wang, Zhuang Hou, Rui Zhang, Meng-bi Guo, and Yanhua Mou
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Antifungal Agents ,Miconazole ,Cell Survival ,medicine.medical_treatment ,Intraperitoneal injection ,Microbial Sensitivity Tests ,Pharmacology ,01 natural sciences ,Mice ,Selenium ,Sterol 14-Demethylase ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Candida albicans ,Candida ,030304 developmental biology ,0303 health sciences ,Binding Sites ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Candidiasis ,Biofilm ,General Medicine ,Metabolism ,biology.organism_classification ,medicine.disease ,Hemolysis ,0104 chemical sciences ,Molecular Docking Simulation ,Fungicide ,Disease Models, Animal ,14-alpha Demethylase Inhibitors ,Biofilms ,Drug Design ,Lead compound ,Half-Life ,medicine.drug - Abstract
A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 μg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 μg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.
- Published
- 2021
13. Comparisons of the restoring and reinforcement effects of carboxymethyl chitosan-silk fibroin (Bombyx Mori/Antheraea Yamamai/Tussah) on aged historic silk
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Weimei Yang, Lingyue Zheng, Jiabing Ran, Wei Dai, Hua Tong, Tong Tong, Fangfang Ni, Xinyu Shen, Xin Wang, and Xinying Hao
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Antifungal Agents ,Silk ,Fibroin ,Biocompatible Materials ,02 engineering and technology ,Moths ,Biochemistry ,law.invention ,03 medical and health sciences ,Crystallinity ,Structural Biology ,Bombyx mori ,law ,Antheraea yamamai ,Animals ,Humans ,Thermal stability ,Crystallization ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Chitosan ,biology ,Tissue Scaffolds ,Chemistry ,Aspergillus niger ,General Medicine ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Bombyx ,SILK ,Aspergillus ,Chemical engineering ,0210 nano-technology ,Fibroins - Abstract
This work presents the results of the reinforcement effects of regenerated silk fibroin solutions (SF) of Bombyx-Mori, Antheraea-Yamamai and Tussah on aged historic silk. Furthermore, Carboxymethyl-chitosan (CMC) was utilized as reinforcement and antibacterial filler to further improving the mechanical properties and antibacterial effects. To clarify the rationale behind this process, comprehensive characterization was applied, and a speculative explanation was provided. The results showed that Bombyx-mori and Tussah have better restoring effects than Antheraea-yamamai. CMC has good compatibility to the SF, and the addition of CMC has significantly contributed to the improvement the mechanical properties and thermal stability of the restored silk, which is due to the formation of chemical bonding, strong hydrogen bonding and the construction of polymer network structure. The enhancement of crystallinity and reduction of β-turns structure indicate that the micro-defects in the crystallization zone of the aged silk has been restored, and the ordered arrangement in the long-range ordered structure has been improved within a certain range. It was found that the CMC acted as antifungal agents when introduced on the aged historic silk, reducing the growth of Aspergillus niger, Aspergillus flavus and Paecilomyces variotii to a certain extent, which were commonly found in storage areas of libraries.
- Published
- 2018
14. Design, Synthesis, Antifungal, and Antioxidant Activities of (E)-6-((2-Phenylhydrazono)methyl)quinoxaline Derivatives
- Author
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Mao Zhang, Jun-Yan Liu, Hai-Liang Zhu, Zhi-Cheng Dai, Jian-Xin Wang, Yu Xiao, Yong-Hao Ye, Shao-Song Qian, and Aimin Lu
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Male ,Models, Molecular ,Antifungal Agents ,Antioxidant ,DPPH ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Chemistry Techniques, Synthetic ,Crystallography, X-Ray ,Antioxidants ,Rhizoctonia ,Lipid peroxidation ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Quinoxaline ,Quinoxalines ,medicine ,Animals ,Organic chemistry ,EC50 ,Carbendazim ,General Chemistry ,chemistry ,Microsomes, Liver ,Microsome ,Lipid Peroxidation ,Trolox ,General Agricultural and Biological Sciences ,Nuclear chemistry - Abstract
Different substituted phenylhydrazone groups were linked to the quinoxaline scaffold to provide 26 compounds (6a-6z). Their structures were confirmed by (1)H and (13)C NMR, MS, elemental analysis, and X-ray single-crystal diffraction. The antifungal activities of these compounds against Rhizoctonia solani were evaluated in vitro. Compound 6p is the most promising one among all the tested compounds with an EC50 of 0.16 μg·mL(-1), more potent than the coassayed positive control fungicide carbendazim (EC50: 1.42 μg·mL(-1)). In addition, these compounds were subjected to antioxidant assay by employing diphenylpicrylhydrazyl (DPPH) and mice microsome lipid peroxidation (LPO) methods. Most of these compounds are potent antioxidants. The strongest compounds are 6e (EC50: 7.60 μg·mL(-1), DPPH) and 6a (EC50: 0.96 μg·mL(-1), LPO), comparative to or more potent than the positive control Trolox [EC50: 5.90 μg·mL(-1) (DPPH) and 18.23 μg·mL(-1) (LPO)]. The structure and activity relationships were also discussed.
- Published
- 2014
15. Fungal Quorum-Sensing Molecules and Inhibitors with Potential Antifungal Activity: A Review
- Author
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Arshad Mehmood, Guorong Liu, Xin Wang, Chengtao Wang, Ya Liu, and Guannan Meng
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quorum-sensing molecules ,Antifungal ,Antifungal Agents ,medicine.drug_class ,Microorganism ,Pharmaceutical Science ,Virulence ,Review ,Analytical Chemistry ,Microbiology ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Drug Discovery ,Cell density ,medicine ,Humans ,Secretion ,Physical and Theoretical Chemistry ,030304 developmental biology ,0303 health sciences ,biology ,030306 microbiology ,antifungal activity ,Organic Chemistry ,quorum-sensing inhibitors ,Fungi ,Biofilm ,Quorum Sensing ,biology.organism_classification ,Quorum sensing ,Mycoses ,Chemistry (miscellaneous) ,Molecular Medicine ,Bacteria - Abstract
The theory of persisting independent and isolated regarding microorganisms is no longer accepted. To survive and reproduce they have developed several communication platforms within the cells which facilitates them to adapt the surrounding environmental changes. This cell-to-cell communication is termed as quorum sensing; it relies upon the cell density and can stimulate several traits of microbes including biofilm formation, competence, and virulence factors secretion. Initially, this sophisticated mode of communication was discovered in bacteria; later, it was also confirmed in eukaryotes (fungi). As a consequence, many quorum-sensing molecules and inhibitors have been identified and characterized in various fungal species. In this review article, we will primarily focus on fungal quorum-sensing molecules and the production of inhibitors from fungal species with potential applications for combating fungal infections.
- Published
- 2019
16. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning
- Author
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Ming Chen, Biao Ren, Guiying Yan, Lixin Zhang, Quan-Xin Wang, and Xing Chen
- Subjects
0301 basic medicine ,Antifungal Agents ,medicine.medical_treatment ,Yeast and Fungal Models ,Semi-supervised learning ,Drug resistance ,Pharmacology ,Pathology and Laboratory Medicine ,Biochemistry ,0302 clinical medicine ,Candida albicans ,Medicine and Health Sciences ,Drug Interactions ,lcsh:QH301-705.5 ,Candida ,media_common ,Fungal Pathogens ,Ecology ,Antimicrobials ,Chemistry ,Drug Information ,High mortality ,Drugs ,Drug Synergism ,Treatment efficacy ,Drug Combinations ,Computational Theory and Mathematics ,Medical Microbiology ,030220 oncology & carcinogenesis ,Modeling and Simulation ,Supervised Machine Learning ,Pathogens ,Adjuvant ,Research Article ,Antifungal ,Drug ,Drug Research and Development ,medicine.drug_class ,media_common.quotation_subject ,Mycology ,Biosynthesis ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Model Organisms ,Microbial Control ,Genetics ,medicine ,Humans ,Microbial Pathogens ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Antifungals ,Drug Screening ,Organisms ,Fungi ,Computational Biology ,Biology and Life Sciences ,Fungal pathogen ,Models, Theoretical ,Yeast ,030104 developmental biology ,lcsh:Biology (General) ,Antimicrobial Resistance - Abstract
Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations., Author Summary Drug combinations represent a promising strategy for overcoming fungal drug resistance and treating complex diseases. There is an urgent need to establish powerful computational methods for systematic prediction of synergistic drug combination on a large scale. Based on the assumption that principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa, NLLSS was developed to predict potential synergistic drug combinations by integrating known synergistic drug combinations, unlabeled drug combinations, drug-target interactions, and drug chemical structures. NLLSS has obtained the reliable performance in the cross validation and experimental validations, which indicated that NLLSS has an excellent performance of identifying potential synergistic drug combinations. Out of 13 predicted antifungal synergistic drug combinations, 7 candidates were experimentally confirmed. It is anticipated that NLLSS would be an important and useful resource by providing a new strategy to identify potential synergistic antifungal combinations, explore new indications of existing drugs, and provide useful insights into the underlying molecular mechanisms of synergistic drug combinations.
- Published
- 2016
17. Synthesis of 1,2,3-triazole hydrazide derivatives exhibiting anti-phytopathogenic activity
- Author
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Yong-Fei Chen, Ling-Ling Cao, Wei Yan, Wang Xing, Zheng-Guang Zhang, Zhi-Cheng Dai, Shengkun Li, Jian-Xin Wang, and Yong-Hao Ye
- Subjects
Fusarium ,Antifungal Agents ,Chemistry Techniques, Synthetic ,010402 general chemistry ,Hydrazide ,01 natural sciences ,Microbiology ,Rhizoctonia solani ,chemistry.chemical_compound ,Drug Discovery ,Mycelium ,Plant Diseases ,Pharmacology ,biology ,010405 organic chemistry ,Organic Chemistry ,Sclerotinia sclerotiorum ,food and beverages ,Biological Transport ,General Medicine ,Plants ,Triazoles ,biology.organism_classification ,0104 chemical sciences ,Fungicide ,chemistry ,Growth inhibition ,Sclerotinia - Abstract
A series of new 1,2,3-triazole derivatives have been prepared and screened for their antifungal activity against phytopathogenic fungi using the mycelium growth inhibition method in vitro . The results indicated that the 1,2,3-triazole hydrazide scaffold displayed significant antifungal activity. Compound 6ad exhibited the most potent anti-phytopathogenic activity, with EC 50 values of 0.18, 0.35, 0.37 and 2.25 μg mL −1 against Rhizoctonia solani , Sclerotinia sclerotiorum , Fusarium graminearum , and Magnaporthe oryzae , respectively. In vivo testing demonstrated that 6ad was effective for the control of rice sheath blight, rape sclerotinia rot, fusarium head blight and rice blast caused by the aforementioned phytopathogens. This work suggests that the combination of 1,2,3-triazole and hydrazide moiety could be a promising fungicide scaffold in the future.
- Published
- 2016
18. Effect of Carbendazim Resistance on Trichothecene Production and Aggressiveness of Fusarium graminearum
- Author
-
Yan-Jun Zhang, Xiao Zhang, Ping-Sheng Fan, Derek W. Hollomon, Chang-Jun Cheng, Jun-Jie Yu, Yan-Nan Zhang, Mingguo Zhou, and Jan-Xin Wang
- Subjects
Fusarium ,Antifungal Agents ,Time Factors ,Pesticide resistance ,Physiology ,Genes, Fungal ,Trichothecene ,Microbial Sensitivity Tests ,Biology ,chemistry.chemical_compound ,Drug Resistance, Fungal ,Gene Expression Regulation, Fungal ,Botany ,polycyclic compounds ,skin and connective tissue diseases ,Mycotoxin ,Triticum ,Carbendazim ,Reproducibility of Results ,food and beverages ,General Medicine ,Fungi imperfecti ,biology.organism_classification ,Fungicide ,Blotting, Southern ,Horticulture ,Gibberella zeae ,chemistry ,Mutagenesis, Site-Directed ,Benzimidazoles ,Carbamates ,Trichothecenes ,Agronomy and Crop Science - Abstract
Fusarium graminearum (teleomorph, Gibberella zeae) causes head blight of cereals and contaminates grains with trichothecene mycotoxins that are harmful to humans and domesticated animals. Control of Fusarium head blight relies on carbendazim (MBC) in China, but resistance to MBC in F. graminearum is now widespread. Sixty-seven strains were evaluated for trichothecene production in shake culture or in the field. The strains included 60 wild-type strains (30 MBC-resistant and 30 MBC-sensitive), three MBC-resistant site-directed mutants at codon 167 in β2-tubulin, three MBC-sensitive site-directed mutants at codon 240 in β2-tubulin, and their MBC-sensitive wild-type progenitor strain ZF21. The incidence of infected spikelets and the amount of F. graminearum DNA in field grain (AFgDNA) also were evaluated for all strains. MBC resistance increased trichothecene production in shake culture or in the field. Although MBC resistance did not change the incidence of infected spikelets, it did increase AFgDNA. Tri5 gene expression increased in MBC-resistant strains grown in shake culture. We found a significant exponential relationship between trichothecene production and Tri5 gene expression in shake culture and a linear relationship between the incidence of infected spikelets or AFgDNA and trichothecene production in field grain.
- Published
- 2009
19. Exophiala asiatica, a new species from a fatal case in China
- Author
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Yu Xin Wang, Dong Ming Li, Duan Li Wang, R. Li, G.S. de Hoog, and Evolutionary Biology (IBED, FNWI)
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,China ,Antifungal Agents ,Black yeast ,Laryngitis ,Young Adult ,Fatal Outcome ,Species Specificity ,stomatognathic system ,Exophiala ,DNA, Ribosomal Spacer ,medicine ,Paralysis ,otorhinolaryngologic diseases ,Humans ,DNA, Fungal ,Mycological Typing Techniques ,Phylogeny ,Fish bone ,Brain Diseases ,biology ,Pharynx ,Pharyngitis ,General Medicine ,Sequence Analysis, DNA ,biology.organism_classification ,medicine.disease ,stomatognathic diseases ,Infectious Diseases ,medicine.anatomical_structure ,Mycoses ,Tonsil ,Female ,Headaches ,medicine.symptom - Abstract
We describe a new species, Exophiala asiatica, isolated from an infection of the pharynx in a 20-year-old, immunocompetent woman in Nanjing, China. The infection was initiated by a fishbone prick in the pharynx, soon developed with facial nodules but subsequently seemed to have disappeared. Tonsil ulceration with progressive soreness of the pharynx was observed 3 years later. Dysphagia, headache and paralysis occurred four years after first signs of infection. Hyphae and yeast-like cells were detected in tissue and a black fungus was recovered repeatedly from pharynx tissue. Despite antifungal therapy for more than one year, the patient died of apparent cerebral dissemination of the etiologic agent. On the basis of morphology, nutritional physiology, ribosomal small subunit DNA and ITS sequence data the strain could not be matched with any existing species. A new species, Exophiala asiatica, is therefore proposed.
- Published
- 2009
20. Genetic basis of haloperidol resistance in Saccharomyces cerevisiae is complex and dose dependent
- Author
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Leonid Kruglyak, Xin Wang, and Copenhaver, Gregory P
- Subjects
Cancer Research ,Saccharomyces cerevisiae Proteins ,Antifungal Agents ,lcsh:QH426-470 ,Quantitative Trait Loci ,Drug Resistance ,Drug resistance ,Saccharomyces cerevisiae ,Microbial Sensitivity Tests ,Quantitative trait locus ,Biology ,Microbiology ,Dose-Response Relationship ,Genetic ,Drug Resistance, Fungal ,Genetic linkage ,Haloperidol ,medicine ,Genetics ,Allele ,Polymorphism ,Molecular Biology ,Gene ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Evolutionary Biology ,Polymorphism, Genetic ,Dose-Response Relationship, Drug ,Strain (biology) ,GTPase-Activating Proteins ,Biology and Life Sciences ,Hydrogen-Ion Concentration ,Genetic architecture ,3. Good health ,lcsh:Genetics ,Fungal ,5.1 Pharmaceuticals ,Generic health relevance ,Development of treatments and therapeutic interventions ,Drug ,Carrier Proteins ,Research Article ,medicine.drug ,Developmental Biology - Abstract
The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance., Author Summary Variation in response to a drug can be determined by many factors. In the model organism baker's yeast, many studies of chemical resistance traits have uncovered a complex genetic basis of such resistance. However, an in-depth study of how drug dose alters the effects of underlying genetic factors is lacking. Here, we employed linkage analysis to map the specific genetic loci underlying response to haloperidol, a small molecule therapeutic drug, using a large panel of segregants from a cross between two genetically divergent yeast strains BY (a laboratory strain) and RM (a vineyard strain). We found that loci associated with haloperidol resistance are dose-dependent. We also showed that variants in the oxysterol-binding-protein-like domain of the gene SWH1 underlie the major locus detected at all doses of haloperidol. Genetic interactions among genes SWH1, MKT1, and IRA2 in the RM background contribute to the differential response at high concentrations of haloperidol.
- Published
- 2014
21. Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives
- Author
-
Shao-Song Qian, Yong-Hao Ye, Hai-Liang Zhu, Shengkun Li, Yong-Fei Chen, Li Shen, Ting-Ting Yang, Mao Zhang, Zhi-Cheng Dai, and Jian-Xin Wang
- Subjects
Fusarium ,Models, Molecular ,Antifungal Agents ,Stereochemistry ,Proton Magnetic Resonance Spectroscopy ,Quantitative Structure-Activity Relationship ,Microbial Sensitivity Tests ,Crystallography, X-Ray ,Biochemistry ,Mass Spectrometry ,Rhizoctonia solani ,chemistry.chemical_compound ,Physical and Theoretical Chemistry ,Mycelium ,biology ,Organic Chemistry ,Sclerotinia sclerotiorum ,Fungi ,Hydrazones ,Triazoles ,biology.organism_classification ,Fungicide ,Phytophthora capsici ,chemistry ,Growth inhibition ,Sclerotinia - Abstract
A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 μg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.
- Published
- 2014
22. Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole
- Author
-
Armand Michoel, Guy Van den Mooter, and Xin Wang
- Subjects
Antifungal Agents ,Pyrrolidines ,Vinyl Compounds ,Materials science ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Dosage form ,Polyethylene Glycols ,Surface-Active Agents ,Differential scanning calorimetry ,Drug Stability ,X-Ray Diffraction ,Phase (matter) ,Organic chemistry ,Solubility ,Dissolution ,Dosage Forms ,chemistry.chemical_classification ,Methylene Chloride ,Calorimetry, Differential Scanning ,Temperature ,Polymer ,Solvent ,chemistry ,Chemical engineering ,Solvents ,Itraconazole ,Ternary operation - Abstract
The purpose of the present study was to characterize the solid state properties of ternary solid dispersions made up of PVP VA64, Myrj 52 and itraconazole. The solid dispersions were prepared by dissolving the materials in methylene chloride, followed by evaporation under reduced pressure of the solvent at 55 °C in a rotovapor. Binary and ternary solid dispersions were characterized by standard and modulated temperature differential scanning calorimetry and X-ray powder diffraction. Although PVP VA64 and itraconazole were found to be completely miscible in the solid state, addition of a small amount of Myrj 52 to the drug–polymer system leads to separation of itraconazole thus demonstrating that Myrj 52 expels the drug from the polymer phase.
- Published
- 2005
23. ASDCD: antifungal synergistic drug combination database
- Author
-
Biao Ren, Guiying Yan, Wei Ren, Ming-Xi Liu, Ming Chen, Xing Chen, Quan-Xin Wang, and Lixin Zhang
- Subjects
Drug ,Antifungal ,Drugs and Devices ,Drug Research and Development ,Antifungal Agents ,Databases, Pharmaceutical ,medicine.drug_class ,media_common.quotation_subject ,Population ,Antifungal drug ,lcsh:Medicine ,Drug resistance ,computer.software_genre ,Biochemistry ,Databases ,Antibiotic resistance ,Drug Discovery ,Humans ,Medicine ,Drug Interactions ,education ,lcsh:Science ,Biology ,media_common ,education.field_of_study ,Multidisciplinary ,Database ,Drug discovery ,business.industry ,lcsh:R ,Fungal Diseases ,Fungi ,Drug Synergism ,Chemical space ,Infectious Diseases ,Mycoses ,Computer Science ,Drug Therapy, Combination ,lcsh:Q ,Information Technology ,business ,computer ,Metabolic Networks and Pathways ,Research Article ,Biotechnology - Abstract
Finding effective drugs to treat fungal infections has important clinical significance based on high mortality rates, especially in an immunodeficient population. Traditional antifungal drugs with single targets have been reported to cause serious side effects and drug resistance. Nowadays, however, drug combinations, particularly with respect to synergistic interaction, have attracted the attention of researchers. In fact, synergistic drug combinations could simultaneously affect multiple subpopulations, targets, and diseases. Therefore, a strategy that employs synergistic antifungal drug combinations could eliminate the limitations noted above and offer the opportunity to explore this emerging bioactive chemical space. However, it is first necessary to build a powerful database in order to facilitate the analysis of drug combinations. To address this gap in our knowledge, we have built the first Antifungal Synergistic Drug Combination Database (ASDCD), including previously published synergistic antifungal drug combinations, chemical structures, targets, target-related signaling pathways, indications, and other pertinent data. Its current version includes 210 antifungal synergistic drug combinations and 1225 drug-target interactions, involving 105 individual drugs from more than 12,000 references. ASDCD is freely available at http://ASDCD.amss.ac.cn.
- Published
- 2014
24. Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents
- Author
-
Fei Liao, Chunyan Chen, Xin Wang, Dan Yang, Xiaolan Yang, Qiao Deng, Zhiqiang Ge, Lvjiang Yuan, and Qinggang Ji
- Subjects
Antifungal Agents ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Aspergillus flavus ,Microbial Sensitivity Tests ,Biochemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Candida albicans ,medicine ,Quinazoline ,Potency ,Enzyme Inhibitors ,Molecular Biology ,Cryptococcus neoformans ,Chitin Synthase ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Chitin synthase ,biology.organism_classification ,In vitro ,Drug Design ,biology.protein ,Quinazolines ,Molecular Medicine ,Fluconazole ,medicine.drug - Abstract
A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b , 5c , 5e , 5f , 5j , 5k , 5l , and 5o had strong inhibitory potency against CHS. Compound 5c , which has the highest potency among these compounds, had a half-inhibition concentration (IC 50 ) of 0.08 mmol/L, while polyoxin B as positive drug had IC 50 of 0.18 mmol/L. These IC 50 values of compounds 5i , 5m , 5n , and 5s were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans , the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus , the activities of 5g , 5l and 5o were16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans , the minimum-inhibition-concentration (MIC) values of compounds 5c , 5d , 5e and 5l were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC 50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents.
- Published
- 2013
25. Development of stabilized itraconazole nanodispersions by using high-gravity technique
- Author
-
Yuan Le, Hong Zhao, Jian-Feng Chen, Zhiliang Zhang, and Jie-Xin Wang
- Subjects
Materials science ,Antifungal Agents ,Scanning electron microscope ,Drug Compounding ,Pharmaceutical Science ,Nanoparticle ,Biological Availability ,Differential scanning calorimetry ,Drug Stability ,Drug Discovery ,Microscopy ,Spectroscopy, Fourier Transform Infrared ,Solubility ,Particle Size ,Dissolution ,Pharmacology ,Organic Chemistry ,Crystallography ,Chemical engineering ,Particle-size distribution ,Microscopy, Electron, Scanning ,Nanoparticles ,Particle size ,Itraconazole ,Gravitation - Abstract
For large scale preparation of stabilized itraconazole (ITZ) nanodispersions to improve the dissolution rate.High-gravity technique was employed to produce ITZ nanodispersions.Stabilizer had a significant effect on the stability of drug nanoparticles. Hydroxypropylmethylcellulose was found to be the most effective stabilizer to prevent drug nanoparticles from aggregation. ITZ nanoparticles with an average size of 210 nm were obtained. Mannitol was the suitable carrier matrix for improving the flowability and the dissolution rate of ITZ nanodispersion. The effects of operating variables on the particle size distribution were investigated in detail. The stability of ITZ nanodispersions was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and in vitro dissolution studies. After 6 months storage, the nanodispersion showed unchanged particles size, morphology, crystal state, chemical structure, and dissolution. In vitro dissolution rate indicated that the nanodispersion could significantly enhance the dissolution rate when compared to the commercial available Sporanox capsules. The nanodispersion achieved 70% of drug dissolution in 10 min, whereas the Sporanox capsules only dissolved 20% during the same period.This study demonstrated that high-gravity technique is a promising method for large scale production of nanodispersions to enhance the dissolution rate of poorly water-soluble drugs.
- Published
- 2012
26. [Cloning and functional analysis of chitinase gene GbCHI from sea-island cotton (Gossypium barbadense)]
- Author
-
Yin-Ping, Ma, Fu-Xin, Wang, Chun-Lin, Yang, Fa-Fu, Shen, and Gui-Xian, Xia
- Subjects
Proteomics ,Gossypium ,Antifungal Agents ,Chitinases ,Molecular Sequence Data ,Amino Acid Sequence ,Cloning, Molecular ,Verticillium - Abstract
Chitinase is one of the important pathogenesis-related (PR) proteins in plants. By comparative proteomics study, a novel pathogen-responsive chitinase (known as GbCHI) has been identified from sea-island cotton (Gossypium barbadense). The GbCHI cDNA was cloned from wilt-resistant sea-island cotton and the anti-fungal activity of the gene product was investigated. qRT-PCR analysis indicated that GbCHI was expressed constitutively in root, stem, leaf, flower, and ovule of cotton plant, and the expression could be induced by Verticillium dahliae and plant hormone SA, ACC, and JA. Subcellular localization analysis using GFP-tagged proteins showed that GbCHI-GFP fusion proteins were targeted mainly to the plasma membrane. Anti-fungal assay demonstrated that GbCHI could inhibit spore germination and hyphae growth of V. dahliae significantly. These results provide important information for understanding the cellular function of GbCHI and for exploring the application potential of this gene in molecular breeding of wilt-tolerant cotton plants.
- Published
- 2012
27. Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp
- Author
-
Xiao-Li Yang, Huanqin Dai, Hui Guo, Biao Ren, Ruinan Yang, Hongwei Liu, Quan-Xin Wang, Lixin Zhang, Liangdong Guo, and Li Bao
- Subjects
Vitamin ,Antifungal Agents ,Stereochemistry ,Fungus ,Bacillus subtilis ,medicine.disease_cause ,chemistry.chemical_compound ,Ascomycota ,Picrates ,Drug Discovery ,Candida albicans ,medicine ,Pharmacology ,biology ,Bacteria ,Molecular Structure ,Biphenyl Compounds ,General Medicine ,Free Radical Scavengers ,biology.organism_classification ,Antimicrobial ,Anti-Bacterial Agents ,chemistry ,Staphylococcus aureus ,Polyketides ,Triol ,Ulocladium - Abstract
Two new polyketides, 7-hydroxy-3, 5-dimethyl-isochromen-1-one (1) and 6-hydroxy-8-methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (2), along with eleven known compounds, 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (3), 7-hydroxy-3-(2-hydroxy-propyl)-5-methyl-isochromen-1-one (4), rubralactone (5), isoaltenuene (6), altenuene (7), dihydroaltenuenes A (8), altenusin (9), alterlactone (10), 6-O-methylnorlichexanthone (11), norlichexanthone (12), and griseoxanthone C (13) were isolated from the culture of the endolichenic fungus Ulocladium sp. Compound 2 was obtained as a racemate with an unprecedented chemical skeleton. The NMR data assignments for 3 and 4 were achieved for the first time. Compounds 1-13 were screened for their antimicrobial and radical scavenging activities. Compound 1 showed some antifungal activity against Candida albicans SC 5314 with IC(50) of 97.93 ± 1.12 μM. Compounds 11-13 showed strong activity against Bacillus subtilis with IC(50) in the range of 1-5 μM. Compound 12 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus with IC(50) of 20.95 ± 1.56 μM. Compounds 9 and 10 showed strong radical scavenging activity in comparison with vitamin C. The plausible biosynthetic pathways for compounds 1, 2, and 4-8 were discussed.
- Published
- 2011
28. Novel cyclic hexapeptides from marine-derived fungus, Aspergillus sclerotiorum PT06-1
- Author
-
Jinkai Zheng, Kui Hong, Yi Wang, Xin Wang, Huajie Zhu, Xiaoping Peng, Peipei Liu, and Weiming Zhu
- Subjects
Models, Molecular ,Staphylococcus aureus ,Antifungal Agents ,Photoisomerization ,Stereochemistry ,Radical ,Molecular Conformation ,Stereoisomerism ,Antineoplastic Agents ,HL-60 Cells ,Microbial Sensitivity Tests ,Crystallography, X-Ray ,Biochemistry ,Peptides, Cyclic ,chemistry.chemical_compound ,Structure-Activity Relationship ,Candida albicans ,Anthranilic acid ,Escherichia coli ,Structure–activity relationship ,Humans ,Physical and Theoretical Chemistry ,Cytotoxicity ,Cell Proliferation ,Organic Chemistry ,Enterobacter aerogenes ,Anti-Bacterial Agents ,Aspergillus ,chemistry ,Pseudomonas aeruginosa ,Halotolerance ,Drug Screening Assays, Antitumor ,Antibacterial activity ,Bacillus subtilis - Abstract
Two novel cyclic hexapeptides containing both anthranilic acid and dehydroamino acid units, sclerotides A (1) and B (2), were isolated from the marine-derived halotolerant Aspergillus sclerotiorum PT06-1 in a nutrient-limited hypersaline medium. Both 1 and 2 are photointerconvertible and could be interconverted via a radical reaction initiated by direct photoisomerization. Both compounds showed moderate antifungal activity. Compound 2 also showed weak cytotoxicity and antibacterial activity.
- Published
- 2009
29. [Two cases with primary lymphadenoid cryptococcosis in children]
- Author
-
Ping, Zhang, Ming, Ma, and Pei-xin, Wang
- Subjects
Male ,Antifungal Agents ,Child, Preschool ,Humans ,Cryptococcosis ,Fluconazole - Published
- 2007
30. Electrospray ionization tandem mass spectrometric analysis of fragmentation patterns of dithiocarbamate derivatives
- Author
-
Xin Wang, Runtao Li, Yaowu Sha, and Xueling Hou
- Subjects
chemistry.chemical_classification ,Spectrometry, Mass, Electrospray Ionization ,Chromatography ,Antifungal Agents ,Protein mass spectrometry ,Molecular Structure ,Chemistry ,Electrospray ionization ,Organic Chemistry ,Selected reaction monitoring ,Extractive electrospray ionization ,Mass spectrometry ,Top-down proteomics ,Analytical Chemistry ,Fragmentation (mass spectrometry) ,Thiocarbamates ,Dithiocarbamate ,Spectroscopy - Published
- 2006
31. [Acute fulminant invasive fungal sinusitis]
- Author
-
Ming, Liu, Bing, Zhou, Hua-chao, Liu, Sheng-zhong, Zhang, Yu-xin, Wang, and Qian, Huang
- Subjects
Male ,Antifungal Agents ,Adolescent ,Debridement ,Mycoses ,Amphotericin B ,Humans ,Female ,Middle Aged ,Sinusitis ,Child ,Aged ,Follow-Up Studies - Abstract
To discuss the clinical presentation, diagnostic criterion and treatment principle of acute fulminant invasive fungal rhinosinusitis (AFFS).Six patients were diagnosed as AFFS based on history, nose, especially eye symptoms with or without fever, sinus CT and MRI, endoscopic and cytological findings in the nasal cavity. Surgical debridement was performed on 5 of 6 biopsy proven AFFS patients, one of them being amputated of the orbital content. With the original disease controlled simultaneously, 4 of 5 patients were prescribed with systemic amphotericin B or liposomal amphotericin B (1 case) and one with Itraconazole orally. One patient had not been involved with any of the anti-fungi measures.Mucor (Zygomycetes) was identified on culture in 1 patient, Rhizopus species in 2, Aspergillus in 1, Alternaria in 1 and mixed Mucor and Rhizopus in 1. All patients were proved of tissue invasion histopathologically through biopsy. One patient died without any anti-fungi therapy on the 7th admission day, 3 patients survived for 88 days, 32 and 6 months respectively and died of original diseases (diabetes 1, leukaemia 2). One patient survived 9 months and lost for follow-up, 1 patient survived 11 months after treatment.A high index of suspicion and early endoscopic investigation through nasal cavity with fungal investigation should highly be strengthened for recognition of this disease. MRI findings should be considered as, or even more, important as that of CT scan on the early diagnoses. Extensive and aggressive surgical debridement, prompt and enough dosage of antifungal therapy intravenously, together with serious controlling of the underlying disease, all take important roles in the complete control of the disease.
- Published
- 2004
32. Study of the phase behavior of polyethylene glycol 6000-itraconazole solid dispersions using DSC
- Author
-
Xin Wang, Armand Michoel, and Guy Van den Mooter
- Subjects
Recrystallization (geology) ,Materials science ,Antifungal Agents ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Polyethylene glycol ,Phase Transition ,law.invention ,Polyethylene Glycols ,Excipients ,chemistry.chemical_compound ,Differential scanning calorimetry ,law ,Phase (matter) ,Organic chemistry ,Crystallization ,Solubility ,chemistry.chemical_classification ,Methylene Chloride ,Calorimetry, Differential Scanning ,Temperature ,Polymer ,chemistry ,Chemical engineering ,Solvents ,Itraconazole ,Dispersion (chemistry) - Abstract
The aim of the present study was to investigate the phase behavior of solid dispersions made up of PEG 6000 and itraconazole using DSC. Solid dispersions were prepared by solvent evaporation. DSC analysis of pure PEG 6000 showed three endothermic events, representing the melting transitions of the three different crystal modifications. It was shown that itraconazole decreased the formation of the polymer modifications with melting transitions at 56 and 59 degrees C but promoted the formation of the modification with a melting transition at 63 degrees C. All dispersions investigated showed the presence of crystalline itraconazole indicating that the drug is not molecularly dispersed in the polymer matrix. However, the presence of an endothermic peak in DSC curves of all solid dispersions at approximately 85-90 degrees C showed that at least a second phase of pure itraconazole is present also: glassy itraconazole. The protective effect of the polymer is clear at low concentration of drug since no recrystallisation exotherm can be detected. However, at drug concentrations at or above 80%, a recrystallization exotherm at approximately 117 degrees C can be detected. At least three different phases can be distinguished at room temperature: a polymer phase, crystalline itraconazole and glassy itraconazole. The findings of the present study thus demonstrate the coexistence of multiple drug phases in a solid dispersion.
- Published
- 2003
33. Proteomic Research Reveals the Stress Response and Detoxification of Yeast to Combined Inhibitors
- Author
-
Ying-Jin Yuan, Ming-Zhu Ding, Wei Liu, Jing-Sheng Cheng, Yang Yang, and Xin Wang
- Subjects
Proteomics ,Antifungal Agents ,Applied Microbiology ,Protein metabolism ,lcsh:Medicine ,Yeast and Fungal Models ,medicine.disease_cause ,Lignin ,chemistry.chemical_compound ,Engineering ,Molecular Cell Biology ,Biological Systems Engineering ,Electrophoresis, Gel, Two-Dimensional ,lcsh:Science ,Acetic Acid ,Cellular Stress Responses ,Multidisciplinary ,biology ,Nucleotides ,Systems Biology ,Microbial Growth and Development ,Agriculture ,Translation (biology) ,Biochemistry ,Genome, Fungal ,Glycolysis ,Research Article ,Biotechnology ,Bioalcohols ,Nitrogen ,Saccharomyces cerevisiae ,Bioengineering ,Microbiology ,Industrial Microbiology ,Model Organisms ,Detoxification ,medicine ,Furaldehyde ,Biology ,Models, Genetic ,Phenol ,lcsh:R ,biology.organism_classification ,Yeast ,Oxidative Stress ,chemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Biofuels ,Fermentation ,Unfolded Protein Response ,Unfolded protein response ,lcsh:Q ,Gels ,Protein Abundance ,Oxidative stress - Abstract
The tolerant mechanism of yeast to the combination of three inhibitors (furfural, phenol and acetic acid) was investigated using 2-DE combined with MALDI-TOF/TOF-MS. The stress response and detoxification related proteins (e.g., Ahp1p, Hsp26p) were expressed higher in the tolerant yeast than in the parental yeast. The expressions of most nitrogen metabolism related proteins (e.g. Gdh1p, Met1p) were higher in the parental yeast, indicating that the tolerant yeast decreases its nitrogen metabolism rate to reserve energy, and possesses high resistance to the stress of combined inhibitors. Furthermore, upon exposure to the inhibitors, the proteins related to protein folding, degradation and translation (e.g., Ssc1p, Ubp14p, Efb1p) were all significantly affected, and the oxidative stress related proteins (e.g., Ahp1p, Grx1p) were increased. Knockdown of genes related to the oxidative stress and unfolded protein response (Grx1, Gre2, Asc1) significantly decreased the tolerance of yeast to inhibitors, which further suggested that yeast responded to the inhibitors mainly by inducing unfolded protein response. This study reveals that increasing the detoxification and tolerating oxidative stress, and/or decreasing the nitrogen metabolism would be promising strategies in developing more tolerant strains to the multiple inhibitors in lignocellulose hydrolysates.
- Published
- 2012
34. Novel Cyclic Hexapeptides from Marine-Derived Fungus, Aspergillus sclerotiorumPT06-1.
- Author
-
Jinkai Zheng, Huajie Zhu, Kui Hong, Yi Wang, Peipei Liu, Xin Wang, Xiaoping Peng, and Weiming Zhu
- Subjects
- *
ORGANIC cyclic compounds , *AMINOBENZOIC acids , *RADICALS (Chemistry) , *CHEMICAL reactions , *PHOTOISOMERIZATION , *ANTIFUNGAL agents , *CELL-mediated cytotoxicity - Abstract
Two novel cyclic hexapeptides containing both anthranilic acid and dehydroamino acid units, sclerotides A (1) and B (2), were isolated from the marine-derived halotolerant Aspergillus sclerotiorumPT06-1 in a nutrient-limited hypersaline medium. Both 1and 2are photointerconvertible and could be interconverted via a radical reaction initiated by direct photoisomerization. Both compounds showed moderate antifungal activity. Compound 2also showed weak cytotoxicity and antibacterial activity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
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