In Vitro Antifungal Activity of Dihydrochelerythrine and Proteomic Analysis in Ustilaginoidea virens

Dihydrochelerythrine(DHCHE)is an isoquinoline compound,which has distinct antifungal activity and can induce apoptosis.The antifungal activity of DHCHE against five rice pathogenic fungi was studied in vitro.At the concentration of 7.5 mg/L,DHCHE exhibited the highest efficacy among tested compounds in inhibiting mycelium growth,with an inhibition rate of 68.8%in Ustilaginoidea virens,which was approximately 2.4 times of that of validamycin(28.7%).After exposure to DHCHE,transmission electron micrographs revealed spores showed incomplete organelles,malformed cell walls and nuclear membranes,as well as irregular lipid spheres.Reactive oxygen species accumulation in treated spores was markedly higher than that in control spores.DHCHE induced cell damage increased in a dose-dependent manner,as indicated by the decrease in mitochondrial membrane potential and initiation of apoptosis.The differences of expression levels of Fip1,ACP1,PMS2 and COX13 that are important for oxidative phosphorylation and mismatch repair pathway were significant,which may be some of the reasons for the induction of apoptosis in DHCHE-treated U.virens.The protein levels of Fip1,ACP1,PMS2 and COX13 agreed with protein fold change ratio from parallel reaction monitoring Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed proteins were further analyzed.These findings will help to elucidate the mechanisms associated with antifungal and pro-apoptotic effects of DHCHE on U.virens,thereby aiding the potential development of novel pesticides.

In Vitro Evaluation of the Antifungal Activity of Essential Oils of Thymus vulgaris and Cymbopogon citratus on Some Strains of Sclerotinia sclerotiorum, Agent Responsible for White Rot of Beans

The present work was aimed to the study of the antifungal activity of essential oils of two aromatic plants against three strains of Sclerotinia sclerotiorum responsible for white rot of bean. The two essential oils (EO) of the studied plants: Thymus vulgaris (HET) and Cymbopogon citratrus (HEC), used at different concentrations: C1 (0.75 ml/ml), C2 (1.5 ml/ml) and C3 (3 ml/ml) presented significant inhibitory activities on the three tested fungal strains namely Bia 1, Bia 2, and Njo 2. Two control treatments (T-: containing no antifungal substance and T+: synthetic fungicide) were also used. The antifungal activity here is related to the inhibition of mycelial growth especially with high concentrations of essential oils. Thus, against S. sclerotiorum, HET showed the highest activity comparable to that of T+ (100% inhibition) at all concentrations on the Bia 1 and Bia 2 strains and at concentration C3 on the Njo 2 strain compared to that of HEC, which certainly inhibited the mycelial growth of the different strains considerably (with a maximum of 78.15% on the Njo 2 strain) but not completely. According to their sensitivity, the Bia 2 strain showed a higher sensitivity to essential oils than the others while the Njo 2 strain was more aggressive. On the basis of MIC50 and MIC90 obtained on the Njo 2 strain, the HET turns out to be the most efficient with respective lower values of (1.73 and 23.34 ml/ml) against (4.76 and 26.03 ml/ml) for the HEC. These EO could thus be exploited as biodegradable antifungal substances, likely to control white rot of bean.

Synthesis,Crystal Structure and Antifungal Activity of a New Ho(Ⅲ) Complex Based on 4,4?-Dicarboxybiphenyl Sulfone

A new lanthanide coordination polymer, [Ho（sba）（H2O）2（DMF）2]？H2O？DMF？Cl （1） based on the versatile ligand H2sba （H2sba = 4,4？-dicarboxybiphenyl sulfone）, was prepared and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis. Single-crystal X-ray diffraction indicates that complex 1 belongs to the triclinic system, space group P with a = 10.6942（6）, b = 11.8452（7）, c = 13.1814（8） ？, α = 94.854（2）, ？ = 96.649（2）, γ = 91.663（2）o, V = 1651.30（17） ？3, Z = 2, Dc = 1.565 g？cm-3, μ = 2.597 mm-1, Mr = 777.98, F（000） = 780, the final R = 0.0446 and wR = 0.1116 with I 〉 2？（I）. In the title complex, the Ho（III） ions exhibit 1D ∞-like double chains. The DMF molecules not only make the structure more stable, but also act as hydrogen bond acceptors making the 1D double chains into a three-dimensional （3D） supramolecular framework. In addition, the antifungal effects of the ligand, metal salt and Ho（III） complex have also been studied by the disc diffusion method against Colletotrichum gloeosporioides Penz. It was found that the antifungal activity of complex 1 was better than the corresponding ligand and the metal salt. Complex 1 has potential applications in the antifungal activity.

Synthesis,Crystal Structure and Antifungal Activity of 2-((2-Fluorobenzyl)thio)-5-(pyridin-4-yl)-1,3,4-oxadiazole

The title compound 2-（（2-fluorobenzyl）thio）-5-（pyridin-4-yl）-1,3,4-oxadiazole（C_（14）H_（10）FN_3OS） was synthesized,and its structure was confirmed by ~1H NMR,MS,elemental analyses and X-ray diffraction. It crystallizes in the monoclinic system,space group P21/n with a = 11.541（16）,b = 8.226（12）,c = 13.683（19） ？,β = 94.872（17）o,V = 1294（3） ？~3,Z = 4 and R = 0.0648 for 2198 observed reflections with I 〉 2σ（I）. The preliminary biological test shows that the title compound has good activity against Pythium ultimum with inhibitory to be 100%.

Synthesis,Crystal Structure,DFT Studies and Antifungal Activity of 5-(4-Cyclopropyl-5-((3-fluorobenzyl)sulfonyl)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole

5-（4-Cyclopropyl-5-（（3-fluorobenzyl）sulfonyl）-4H-1,2,4-triazol-3-yl）-4-methyl-1,2,3-thiadiazole was synthesized and recrystallized from Et OH. The compound was characterized by ^1H NMR,MS,elemental analysis and X-ray diffraction. The structure-active relationship and the antifungal activity based on density functional theory calculation（DFT） and antifungal activities were investigated. The compound crystallizes in the monoclinic space group P121/n1 with a = 8.929（3）,b=12.715（4）,c=15.161（5） A°,β = 106.142（3）o,V = 1653.3（9） A°3,Z = 4 and R = 0.0393 for 3930 observed reflections with I 〉 2σ（I）. Theoretical calculation of the title compound was carried out with B3LYP/6-31G（d,p）. The full geometry optimization was carried out using the 6-31G（d,p） basis set.The frontier orbital energy and atomic net charges were discussed. The observed results of the compound have been compared with theoretical results and the experimental data show good agreement with the calculated values. The compound exhibits good antifungal activity.

Synthesis,Crystal Structure and Antifungal Activity of N-((2,6-Difluorophenyl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide

The title compound N-（（2,6-difluorophenyl）carbamoyl）-1,3-dimethyl-1 H-pyrazole-4-carboxamide（C13H12F2N4O2） was synthesized, and its structure was confirmed by ^1H NMR,HRMS and X-ray diffraction. It crystallizes in the monoclinic system, space group P21/c with a = 9.50（2）, b = 10.11（2）, c = 14.07（3） A^°, β = 102.15（3）°, Dc = 1.480 g/cm^3, Z = 4, V = 1320（5） A^°3, the final R = 0.0789 and wR = 0.1860 for 1054 observed reflections with I 〉 2σ（I）. The preliminary biological test shows that the title compound has weak antifungal activities.

A New Co(Ⅱ)Coordination Compound Constructed by Tripyridyltriazole and Pyromellitic Acid:Synthesis,Crystal Structure and Antifungal Activity

A new coordination compound, [Co（L223）2（H2O）2]·H2pm（1, L223 = 3,4-bis（2-pyridyl）-5-（3-pyridyl）-1,2,4-triazole and H4 pm = pyromellitic acid）, has been synthesized. The structure of complex 1 has been characterized by X-ray single-crystal diffraction, elemental analysis, IR spectrum analysis and thermogravimetric analysis. Single-crystal X-ray diffraction analysis reveals that complex 1 belongs to the triclinic system, space group P1 with a = 10.2470（8）, b = 10.2879（9）, c = 10.2951（11） ？, α = 109.398（2）, β = 97.6590（10）, γ = 95.3260（10）°, V = 1003.60（16） ？3, Z = 1, Dc = 1.565 g/cm^3, μ = 0.508 mm%^-1, Mr = 945.73, F（000） = 485, the final R = 0.0562 and w R = 0.0783 with I 〉 2σ（I）. Two L223 as chelating ligands link one Co（II） ion to form a 0D motif. Furthermore, the 0D motifs are linked into a 2D coordination pattern with hydrogen bonds. In addition, the antifungal effects of the ligand and the complex were evaluated by the disc diffusion method against Colletotrichum gloeosporioides Penz. 1 represents antifungal activity with high levels of inhibitory potency which is larger than the corresponding ligand.

Synthesis,Crystal Structure and Antifungal Activity of 8-Chloro-3-((4-chlorobenzyl)-thio)[1,2,4]triazolo[4,3-a]pyridine

The title compound 8-chloro-3-（（4-chlorobenzyl）thio）-[1,2,4]triazolo[4,3-a]pyridine was prepared from 1-chloro-4-（chloromethyl）benzene and 8-chloro-[1,2,4]triazolo[4,3-a]pyridine-3（2H）-thione in the presence of Na OH, and its structure was determined by X-ray diffraction analysis. The crystal is of triclinic system, space group P1 with a = 6.8264（6）, b = 7.5890（4）, c = 13.0960（7） A, α = 93.447（4）, β = 98.772（6）, γ = 92.615（6）o, V = 668.26（8） A3, Z = 2, the final R = 0.035 and wR = 0.09 for 2259 observed reflections with I 〉 2σ（I）. The preliminary biological test showed that the title compound has activities against Stemphylium lycopersici（Enjoji） Yamamoto, Fusarium oxysporum. sp. cucumebrium, and Botrytis cinerea with inhibitory to be 51.19%, 62.02% and 15.56%, respectively.

Essential Oil from Inula britannica Extraction with SF-CO_2 and Its Antifungal Activity

The aim of this study was to determine the extraction technique of supercritical fluid carbon dioxide（SF-CO 2） for the essential oil from Inula britannica flowers and its antifungal activities against plant pathogenic fungi for its potential application as botanical fungicide.The effects of factors,including extraction temperature,extraction pressure,SF-CO 2 flow rate,flower powder size,and time on the essential oil yield were studied using the single factor experiment.An orthogonal experiment was conducted to determine the best operating conditions for the maximum extraction oil yield.Adopting the optimum conditions,the maximum yield reached 10.01% at 40°C temperature,30 MPa pressure,60 mesh flower powder size,20 L h-1SF-CO 2 flow rate,and 90 min extraction time.The antifungal activities of I.britannica essential oil using the SF-CO 2 against the most important plant pathogenic fungi were also examined through in vitro and in vivo tests.Sixteen plant pathogenic fungi were inhibited to varying degrees at 1 mg mL-1concentration of the essential oil.The mycelial growth of Gaeumannomyces graminis var.tritici was completely inhibited.The radial growths of Phytophthora capsici and Fusarium monilifome were also inhibited by 83.76 and 64.69%,respectively.In addition,the essential oil can inhibit the spore germination of Fusarium oxysporum f.sp.vasinfectum,Phytophthora capsici,Colletotrichum orbiculare,and Pyricularia grisea,and the corresponding inhibition rates were 98.26,96.54,87.89,and 87.35% respectively.The present study has demonstrated that the essential oil of I.britannica flowers extracted through the SF-CO 2 technique is one potential and promising antifungal agent that can be used as botanical fungicide to protect crops.

Design, Synthesis and Antifungal Activity of 6-Fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]-quinoline-2-carboxamide Derivatives

A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.

Studies on the synthesis and antifungal activity of thiochromanone derivatives

In this paper nine New Mannich bases of 6-fluoro-thiochromanone and eight new 3-substituted-6.8-dichloro thiochromanones were synthesized and their structures were confirmed by IR, H-1-NMR and elementary analysis. Most of these compounds showed excellent antifungal activity.

Antifungal activity of various essential oils against Saccharomyces cerevisiae depends on disruption of cell membrane integrity

Antifungal activity and mode of action of nine essential oils(EOs)against S.cerevisiae cells were examined.Antifungal effects of commercial lemon peel,orange peel,tea tree,turpentine,rosemary,peppermint,thyme,oregano and clove oils were determined through Minimum Inhibitory Concentration(MIC),Minimum Fungicidal Concentration(MFC)and inhibition zone measurements.The most effective oil was turpentine oil.Orange peel,thyme and oregano oils were also effective,according to MIC and MFC.Inhibition zone measurements,also revealed oregano,orange peel,thyme,turpentine and clove oils as most efficient ones.Later,membrane damage of yeast cells was studied by measuring the extracellular pH and conductivity in a concentration dependent manner.Orange peel,turpentine,thyme and oregano oils caused a clear increase in extracellular pH of glucose-induced yeast cells and induced an increase in extracellular conductivity.These results point to the deterioration of yeast cell membrane integrity upon exposure to EOs.Since these oils can be used as food preservatives and pharmaceutical agents,it is very important to understand their mode of action and their main target sites in the cell.Thus this research not only opens new perspectives to understand antifungal activity mechanisms of EOs,but also help widen their use.

Antifungal Activity of Crude Extracts of Tectona grandis L.f. against Wood DecayFungi

Wood is mainly made up of cellulose, hemicelluloses, lignin polymers and other organic and inorganic substances, making it susceptible to deteriorate by various biological agents. Tectona grandis L.f. (Teak) is a timberspecies with high resistance to biological deterioration, valued for its durability, beauty, and mechanical resistance.The purpose of this work was to evaluate the antifungal activity of crude extracts from teak on various fungi thatcause wood deterioration. For this, Teak heartwood was obtained, then fragmented and pulverized until obtaininga flour which was used for compounds extraction using the Soxhlet technique coupled to a rotary evaporatorthrough solvents of increasing polarity (hexane, dichloromethane, tetrahydrofuran, and acetone). The extractsobtained were tested against fungal organisms collected in the field, and the LC50 was determined using teak crudeextracts on Artemia salina as a biological model. The results obtained showed that a high flour yield was obtainedwith hexane (0.951 g), followed by tetrahydrofuran (0.446 g), dichloromethane (0.348 g), and acetone (0.152 g). Byusing nine fungal organisms that predominantly correspond to the genus Aspergillus, the extractable compoundswere tested, inhibiting 25% of mycelial growth with tetrahydrofuran (T. versicolor), and 40.9% with dichloromethane(G. trabeum). Likewise, the biological model of A. salina showed an LC50 of 84.9 μg/mL with hexane, 43.3 μg/mLwith dichloromethane, 59.6 μg/mL with tetrahydrofuran, and 54.7 μg/mL with acetone. For this reason, it is concluded that Teak wood contains many extractable compounds in relation to its weight, besides having antimicrobialactivity when extracted through polar compounds such as dichloromethane and tetrahydrofuran.

Antifungal Activity and Toxicity of Two New types of Polyene Antibiotics against Four Species of Rice Pathogenic Fungi

The antifungal activity and toxicity of new type polyene macrolide antibiotics-Antifungalmycin 702 and Fungichromin against Rhizoctonia solani, Hel- minthosporium sigmoideum Car. , Magnaporthe grisea and Ustilaginoidea virens were studied by mycelial growth rate method and mycelial dry weight method in vitro. The results showed that both of Antifungalmycin 702 and Fungichromin had strong antifungal activity against four speices of rice pathogenic fungi. Treated with 50 μmL Antifungalmycin 702 , the inhibitory rates of Antifungalmycin 702 agmnst R. solani, H. sigmoideum Cav., M. grisea and U. virens were 100%, 100%,91.20% and 68.10%, and EC50 and ECho were 7.00, 10.30, 14.41, 26.71 and 13.20, 17.66, 27.67,128.28 p.g/mL, respectively. Treated with 13 pg/mL Fungichremln, the inhibitory rates of Fungichromin against four speices of rice pathogenic fungi were 78.20%, 100%, 100% and 79.17%, and ECs0 and ECg0 were 1.47, 1.91, 2.37, 0. 20 and 41. （15, 3.92, 4.34, 135.54 gg/mL, respectively. The antifungal activity of Fungichromin was stronger than Antifungalmycin 702.

Expression of Fragaria ananassa Osmotin-like Protein(FaOLP2) in E. coli:Purification and Antifungal Activity

[ Objective] The FaOLtr2 （ Frago^ia ananassa osmotin-like protein） is a functional homolog of PR5-1ike protein. This study was undertaken to produce recombinant FaOLP2 and to identify its antifungal activity. [ Method] The ORF of FaOLP2 （ accession number DQ325524） was cloned into pET22b vector to con- stroct the pET22b-FaOLP2 plasmid. The recombinant mature FaOLP2 was expressed in E. coli Rosetta-gami B （DE3） by inducing with I nunol/L IPTG and found exclusively in insoluble inclusion bodies. As FaOLP2 requires the correct formation of eight disulfide bonds, but there were no obvious effect to correctly form these by expression at different temperatures and high osmotic pressure （ supplemented Betaineand and D-Sorbitol）, we used an in vitro method to refold E. coli expressed FaOLP2 by gradually elution using reduced：oxidized gluthatione redox buffer, followed by 8 mol/L urea solubilized His6-tagged mature FaOLP2 protein, which was affinity-purified by an immobilized-metal （Ni2＋ ） affinity chromatography （IMAC） column. [ Result] This method generated biologically active conformations of the recombinant mature FaOLP2 that displayed antifungal activity against Ustilaginoides virens, a plant pathogenic fungus, which causes rice false smut. [ Conclusion] This study laid the foundation for further biotechnological application of the novel protein.

A New 3d-4f Heterobimetallic Complex Based on 4,4′-Dicarboxybiphenyl Sulfone:Synthesis,Crystal Structure and Antifungal Activity

A new 3 d-4 f heterobimetallic complex [PrCu（sba）2（Hsba）（H2 O）3]·H2 O（1） based on a versatile ligand H2 sba（H2 sba = 4,4？-dicarboxybiphenyl sulfone） was prepared and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis. Single-crystal X-ray diffraction indicates that complex 1 belongs to the monoclinic system, space group P21/n with a = 12.4642（11）, b = 16.0586（16）, c = 21.9678（19） ？, β = 92.888（1）o, V = 4391.4（7） ？3, Z = 4, Dc = 1.800 g·cm-3, μ = 1.812 mm-1, Mr = 1190.31, F（000） = 2388, the final R = 0.0663 and wR = 0.1539 for 7737 observed reflections with I 〉 2s（I）. Complex 1 exhibits 2D network skeletons which are linked by hydrogen-bonding interactions to give a 3D supramolecular architecture. In addition, the antifungal effects of H2 sba, metal salts and the title complex have also been studied by disc diffusion method against Colletotrichum gloeosporioides Penz. Complex 1 has better antifungal activity than H2 sba and the corresponding metal salts. Complex 1 has potential applications in the antifungal activity.

Evaluation of the Antifungal Activity of Aqueous and Alcoholic Extracts of Six Spices

Background: Nigeria is plagued with a variety of socioeconomic problems mainly poverty, poor access to quality healthcare and poor hygienic conditions resulting in the myriad of fungal infections that are frequently encountered in clinical practice. Method: The antifungal activity of aqueous, methanolic, propanolic and benzyl alcohol extracts of Capsicum annuum fruits and seeds, Capsicum chinense fruits and seeds, Aframomum melegueta pods and seeds, Allium sativum bulbs, Allium cepa bulbs and Zingiber officinale rhizomes on Candida albicans (yeast), Aspergillus niger (mould) and Trichophyton rubrum (dermatophyte) were evaluated by the agar well diffusion method. The aqueous and alcoholic filtered plant extracts were obtained by maceration, and also methanolic extracts were also obtained by Soxhlet extraction. The results were obtained by measuring the inhibition zone diameter in millimeters and were presented by subtracting the activity of the control. Results: Aqueous and methanolic extracts of Allium sativum gave the highest inhibition of the growth of Candida albicans (22 mm), followed closely by its propanolic extract with inhibition zone diameter of 15 mm, and also, propanolic extracts of Aframomum melegueta and Allium cepa gave inhibition zone diameters of 12 mm each. Soxhlet methanolic extract of Allium sativum had the highest inhibition of the growth of Aspergillus niger with an inhibition zone diameter of 25 mm, followed closely by Zingiber officinale Soxhlet methanolic extract with an inhibition zone diameter of 22 mm, also, the propanolic extract of Allium sativum gave an inhibition zone diameter of 21 mm, whereas Soxhlet methanolic extracts of Aframomum melegueta and Allium cepa gave an inhibition zone diameter of 19 mm each. The highest activity against Trichophyton rubrum was obtained with the Soxhlet methanolic extract of Allium sativum (39 mm), followed closely by its propanolic extract with an inhibition zone diameter of 27 mm. An inhibition zone diameter of 22 mm was recorded with the benzyl alcohol extract of Allium cepa, 22 mm with the Soxhlet methanolic extract of Aframomum melegueta and 19mm with the aqueous extract of Capsicum chinense seeds. Conclusion: The in-vitro inhibitory effects of these spice extracts indicated that the test spices could serve as potential candidates for developing new systemic and topical antifungal drugs against the wide range of pathogenic fungal strains, and they could also serve as natural prophylaxis against the fungal infections.

Antifungal Activity of Oleoresin and Fractions of Pinus elliottii Engelm and Pinus tropicalis against Phytopathogens

Microorganism resistance to the existing products is yet another difficulty that agriculturalists have to deal with. In this context, the search for new agricultural products that can fight phytopathogens has become increasingly important. Plants have played an important role in this process, because they can serve as a source of new compounds for drug discovery. Plants belonging to the genus Pinus produce an oleoresin that protects the plant against herbivores and pathogens. With a view to developing products that can combat fungal pathogens without harming the environment, this work aimed to evaluate the antifungal activity of the oleoresins and fractions of Pinus elliottii Engelm and Pinus tropicalis against phytopathogens. The methodology based on NCCLS M38-A standards aided antifungal activity assessment. The microdilution method helped to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). The oleoresins of P. elliottii and P. tropicalis afforded the most significant results—they displayed fungicidal activity against all the tested species. MIC values were promising, especially the MIC of the oleoresin of P. elliottii against S. rolfsii (1.95 μg·mL-1). The MIC values of the oleoresins of P. elliottii and P. tropicalis ranged from 1.95 to 1000 μg·mL-1 and from 31.25 to 250 μg·mL-1, respectively. Fraction PT2 of P. tropicalis furnished the best results among all the assayed fractions: MIC values lay between 125 and 500 μg·mL-11. In conclusion, the oleoresin of P. tropicalis is a promising source of new antifungal agents for application in the treatment of phytopathogenic infections.

Bioactive chemical constituents from the marine-derived fungus Cladosporium sp.DLT-5

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus Nigrospora sp.QQYB1

Marine microorganisms have long been recognized as potential sources for drug discovery.Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades.In this study,12 new griseofulvin derivatives[(±)-1-2,(+)-3,(±)-4,10-12,and 14-15]and two new griseofulvin natural products(9 and 16)together with six known analogues[(-)-3,5-8,and 13]were isolated from the mangrove-derived fungus Nigrospora sp.QQYB1 treated with 0.3%NaCl or 2%NaBr in rice solid medium.Their 2D structures and absolute configurations were established by extensive spectroscopic analysis(1D and 2D NMR,HRESIMS),ECD spectra,computational calculation,DP4+analysis,and X-ray single-crystal diffraction.Compounds 1-4 represent the first griseofulvin enantiomers with four absolute configurations(2S,6'S;2R,6'R;2S,6'R;2R,6'S),and compounds 9-12 represent the first successful production of brominated griseofulvin derivatives from fungi via the addition of NaBr to the culture medium.In the antifungal assays,compounds 6 and 9 demonstrated significant inhibitory activities against the fungi Colletotrichum truncatum,Microsporum gypseum,and Trichophyton mentagrophyte with inhibition zones varying between 28 and 41 mm(10μg/disc).The structure-activity relationship(SAR)was analyzed,which showed that substituents at C-6,C-7,C-6'and the positions of the carbonyl and double bond of griseofulvin derivatives significantly affected the antifungal activity.