ABSTRACT
Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.
Subject(s)
Hypericum , Sesquiterpenes , Anti-Inflammatory Agents/chemistry , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Hydrogen Peroxide , Molecular Docking Simulation , NF-kappa B/metabolism , Microglia/metabolism , Circular Dichroism , Nitric Oxide , Nitric Oxide Synthase Type II/metabolismABSTRACT
Five new diterpenoids, named euphorfischerins A-E, were isolated from the roots of Euphorbia fischeriana. Their chemical structures and absolute configurations were determined by interpretation of NMR, HR-ESI-MS, ECD and X-ray diffraction data. Euphorfischerin A showed cytotoxicity against the human cancer cell lines HeLa, H460 and Namalwa with IC50 values of 4.6, 11.5 and 16.4â µM, respectively, while euphorfischerin B gave comparable IC50 values of 9.5, 17.4 and 13.3â µM against the three cancer cell lines, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Euphorbia/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Humans , Models, Molecular , Neoplasms/drug therapy , Plant Roots/chemistryABSTRACT
BACKGROUND: Natural meroterpenes derived from phloroglucinols and ß-caryophyllene have shown high inhibitory activity against α-glucosidase or cancer cells, however, the chemical diversity of this type of skeletons in Nature is limited. METHODS: To expand the chemical space and explore their inhibitory activities against α-glucosidase (EC 3.2.1.20), we employed ß-caryophyllene and some natural moieties (4-hydroxycoumarins, lawsone or syncarpic acid) to synthesize new types of meroterpene-like skeletons. All the products (including side products) were isolated and characterized by NMR, HR-MS, and ECD. RESULTS: In total, 17 products (representing seven scaffolds) were generated through a one-pot procedure. Most products (12 compounds) showed more potential activity (IC50 < 25 µM) than the positive controls (acarbose and genistein, IC50 58.19, and 54.74 µM, respectively). Compound 7 exhibited the most potent inhibition of α-glucosidase (IC50 3.56 µM) in a mixed-type manner. The CD analysis indicated that compound 7 could bind to α-glucosidase and influence the enzyme's secondary structure. CONCLUSIONS: Compound 7 could serve as a new type of template compound to develop α-glucosidase inhibitors. Full investigation of a biomimic reaction can be used as a concise strategy to explore diverse natural-like skeletons and search for novel lead compounds.
Subject(s)
Biomimetic Materials/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Polycyclic Sesquiterpenes/pharmacology , Terpenes/pharmacology , Kinetics , Magnetic Resonance Spectroscopy , Terpenes/chemical synthesis , Terpenes/chemistryABSTRACT
Emerging fungal phytodiseases are a food security threat and novel fungicides are in an urgent need. Herein, a series of isobutyrophenone derivatives were designed and synthesized. The derivatives exhibited excellent fungicidal activities against seven fungi. The structure-activity relationship (SAR) study indicated that the introduction of a bromo group at the position 3 or 5 of the phenyl ring, as well as esterification of the 4-hydroxy with a chloroacetyl group, could substantially increase the antifungal activity and spectrum of the compounds. Among all 23 compounds, 2-bromo-3-hydroxy-4-isobutyryl-6-methylphenyl 2-chloroacetate (12b) showed the highest fungicidal activity against all seven tested fungal pathogens with EC50 values ranging from 1.22 to 39.94⯵g/mL and exhibited the most potent inhibition against class II fructose-1,6-bisphosphate aldolase with an IC50 of 3.63⯵M. The lead compounds were proven to be safe to NIH3T3/293â¯T cells and silkworm larvae, and relatively stable under different harsh conditions. Detached fruit tests showed the practical potential of lead compounds for fruit (or plant) protection. Taken together, our results indicated that the isobutyrophenone derivatives could be further optimized and developed as advanced leads for new fungicides.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/metabolism , Fructose-Bisphosphate Aldolase/metabolism , Animals , Bombyx/metabolism , Cell Line , Fructose-Bisphosphate Aldolase/genetics , Humans , Larva/metabolism , Mice , Microbial Sensitivity Tests , Molecular Structure , NIH 3T3 Cells , Structure-Activity RelationshipABSTRACT
Based on benzoxazole and benzothiazole scaffold as an important pharmacophore, two series of 2-(aryloxymethyl) benzoxazole and benzothiazole derivatives were synthesized and their antifungal effects against eight phytopathogenic fungi were evaluated. Compounds 5a, 5b, 5h, and 5i exhibited significant antifungal activities against most of the pathogens tested. Especially 5a, 5b, 5h, 5i, 5j, and 6h inhibited the growth of F. solani with IC50 of 4.34â»17.61 µg/mL, which were stronger than that of the positive control, hymexazol (IC50 of 38.92 µg/mL). 5h was the most potent inhibitor (IC50 of 4.34 µg/mL) against F. Solani, which was about nine times more potent than hymexazol. Most of the test compounds displayed significant antifungal effects against B. cinerea (IC50 of 19.92â»77.41 µg/mL), among them, 5a was the best one (IC50 of 19.92 µg/mL). The structure-activity relationships (SARs) were compared and analyzed. The result indicates that the electron-drawing ability and position of the substituents have a significant impact on biological activities. Furthermore, docking studies were carried out on the lipid transfer protein sec14p from S. cerevisiae, and preliminarily verified the antifungal activities. Taken together, these results provide 2-(phenoxymethyl)benzo[d]oxazole as an encouraging framework that could lead to the development of potent novel antifungal agents.
Subject(s)
Antifungal Agents/chemistry , Benzothiazoles/chemistry , Benzoxazoles/chemistry , Structure-Activity Relationship , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Benzothiazoles/chemical synthesis , Benzothiazoles/pharmacology , Benzoxazoles/chemical synthesis , Benzoxazoles/pharmacology , Fungi/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Saccharomyces cerevisiae/drug effectsABSTRACT
A series of acetophenone derivatives (10a-10i, 11, 12a-12g, 13a-13g, 14a-14d and 15a-15l) were designed, synthesized and evaluated for antifungal activities in vitro and in vivo. The antifungal activities of 53 compounds were tested against several plant pathogens, and their structure-activity relationship was summarized. Compounds 10a-10f displayed better antifungal effects than two reference fungicides. Interestingly, the most potent compound 10d exhibited antifungal properties against Cytospora sp., Botrytis cinerea, Magnaporthe grisea, with IC50 values of 6.0-22.6⯵g/mL, especially Cytospora sp. (IC50â¯=â¯6.0⯵g/mL). In the in vivo antifungal assays, 10d displayed the significant protective efficacy of 55.3% to Botrytis cinerea and 73.1% to Cytospora sp. The findings indicated that 10d may act as a potential pesticide lead compound that merits further investigation.
Subject(s)
Acetophenones/pharmacology , Ascomycota/drug effects , Biological Products/pharmacology , Botrytis/drug effects , Fungicides, Industrial/pharmacology , Magnaporthe/drug effects , Acetophenones/chemical synthesis , Acetophenones/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Dose-Response Relationship, Drug , Drug Design , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity RelationshipABSTRACT
Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by 1H, 13C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity. On the other hand, for the first time, these compounds were also assayed as potential inhibitors against Class II fructose-1,6-bisphosphate aldolase (Fba) from the rice blast fungus, Magnaporthe grisea. Compounds 5e and 5g were found to exhibit the inhibition constants (Ki) for 15.12 and 14.27⯵M, respectively, as the strongest competitive inhibitors against Fba activity. The possible binding-modes of compounds 5e and 5g were further analyzed by molecular docking algorithms. The results strongly suggested that compound 5g could be a promising lead for the discovery of new fungicides via targeting Class II Fba.
Subject(s)
Antifungal Agents/pharmacology , Biological Products/pharmacology , Butyrophenones/pharmacology , Enzyme Inhibitors/pharmacology , Fructose-Bisphosphate Aldolase/antagonists & inhibitors , Magnaporthe/drug effects , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Butyrophenones/chemical synthesis , Butyrophenones/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Fructose-Bisphosphate Aldolase/metabolism , Magnaporthe/enzymology , Magnaporthe/growth & development , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Structure-Activity RelationshipABSTRACT
Secondary metabolites, particularly the grayanane diterpenoids produced by the members of genus Pieris, have been investigated in past decades for their remarkable antifeedant and insecticidal activities and toxicity. Grayanoids exhibit diverse biological properties such as antifeedant, insecticidal, cAMP regulatory, and sodium-channel-modulating activities. Structural complexity and diverse bioactivity of grayanoids have made them attractive targets for chemical, biological, and synthetic purposes. The current review synthesized findings published from 1966 to 2017, which include 135 reports that describe 130 terpenoids, including 103 grayanoids. The distribution, structure, skeleton, as well as the antifeedant and insecticidal activity of terpenoids, particularly the grayanane diterpenoids, are discussed in detail in this review. In cases where sufficient information is available, the structure-activity relationships of their antifeedant activity are also presented. We hope that this contribution will prompt more scientists to pay attention to these diterpenoids, which may be potentially applied in the agricultural field.
Subject(s)
Ericaceae/chemistry , Insecticides/chemistry , Insecticides/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Terpenes/chemistry , Terpenes/pharmacology , Animals , Insecta/drug effects , Insecta/physiology , Structure-Activity RelationshipABSTRACT
A series of new 2,4-dihydroxy-5-methylacetophenone 2 derivatives were synthesized, and characterized by (1)H, (13)C NMR and ESI-MS. Their antifungal activities were evaluated in vitro against five important plant fungal pathogens including Cytospora sp., Glomerella cingulate, Pyricularia oryzaecar, Botrytis cinerea and Alternaria solani by the mycelial growth inhibitory rate assay. Compounds 2b-d, 2g and 2h displayed a broad-spectrum activity. The logP value of these active compounds is ranging from 1.71 to 2.54. Especially, isopropyl ketone 2g (logP 2.27) was found to be the most active to the tested organisms with IC50 values of 17.28-32.32 µg/mL. The results suggest that compound 2g might be a promising candidate in the development of new agrochemical antifungal agents. Preliminary structure-activity relationship (SAR) studies of the acetophenone derivatives are also discussed.
Subject(s)
Acetophenones/pharmacology , Fungicides, Industrial , Acetophenones/chemical synthesis , Acetophenones/chemistry , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Inhibitory Concentration 50 , Mitosporic Fungi , Phyllachorales , Structure-Activity RelationshipABSTRACT
A series of 17 simple 1-(2,4-dihydroxyphenyl) ethanones were synthesised, and their structures characterised by (1)H, (13)C NMR and ESI-MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi including Glomerella cingulate, Botrytis cirerea, Fusarium graminearum, Curvularia lunata and Fusarium oxysporum f. sp. vasinfectum by the mycelial growth inhibition assay. Compounds 2g and 2h exhibited broad-spectrum inhibitory activity against the mycelial growth of the tested pathogens with IC50 values in the range of 16-36 µg/mL, and in particular being more active to G. cingulate, with IC50 values of 16.50 and 19.25 µg/mL, respectively, than the other pathogens. Preliminary SAR indicated that an α,ß-unsaturated ketone unit of the alkyl chain of the compounds is the structure requirement for fungicidal action. The results suggested that 2g and 2h may be promising leads in the development of new antifungal agents.
Subject(s)
Acetophenones/pharmacology , Fungicides, Industrial/pharmacology , Acetophenones/chemical synthesis , Ascomycota/drug effects , Biological Products , Botrytis/drug effects , Fungicides, Industrial/isolation & purification , Fusarium/drug effects , Inhibitory Concentration 50 , Structure-Activity RelationshipABSTRACT
The aim of the present study was to investigate the regulatory effects of histone methylation modifications on the expression of miR-200c, as well as invasion and migration of gastric carcinoma cells. Gastric carcinoma cell line, MGC-803, were treated by 2.5 µmol/L histone methyltransferase inhibitor, DZNep. The expression of miR-200c was detected by real-time quantitative PCR (qRT-PCR). The epithelial-mesenchymal transition (EMT) indicators (ZEB1/2 and E/N-cadherin), EZH2, EED, SUZ12 and H3K27me3 expressions were detected by Western blot. Cell migration and invasion abilities were detected by Transwell and scratch tests. The result showed that, compared with DMSO (control) group, DZNep significantly increased the expression of miR-200c to about 2.1 times, inhibited ZEB1, ZEB2, and N-cadherin expressions, and activated E-cadherin expression; Also, DZNep decreased the protein expressions of EZH2, EED, SUZ12 and H3K27me3; Moreover, DZNep could inhibit MGC-803 cell invasive and migrative abilities, as well as MMP9 expression. These results suggest DZNep raises miR-200c expression to delay the invasion and migration of gastric carcinoma cells, and the underlying mechanisms involve the regulations of EMT-related proteins and polycomb repressive complex 2.
Subject(s)
Adenosine/analogs & derivatives , Cell Movement/drug effects , MicroRNAs/metabolism , Protein Methyltransferases/antagonists & inhibitors , Adenosine/pharmacology , Cadherins/metabolism , Cell Line, Tumor/drug effects , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/metabolism , Humans , Repressor Proteins/metabolism , Transcription Factors/metabolism , Zinc Finger E-box Binding Homeobox 2 , Zinc Finger E-box-Binding Homeobox 1ABSTRACT
The expression levels of microRNAs (miRNAs) including miR-21, have been reported to change in response to traumatic brain injury (TBI), suggesting that they may influence the pathophysiological process in brain injury. To analyze the potential effect of miR-21 on neurological function after TBI, we employed the fluid percussion injury rat model and manipulated the expression level of miR-21 in brain using intracerebroventricular infusion of miR-21 agomir or antagomir. We found that upregulation of miR-21 level in brain conferred a better neurological outcome after TBI by improving long-term neurological function, alleviating brain edema and decreasing lesion volume. To further investigate the mechanism underlying this protective effect, we evaluated the impact of miR-21 on apoptosis and angiogenesis in brain after TBI. We found that miR-21 inhibited apoptosis and promoted angiogenesis through regulating the expression of apoptosis- and angiogenesis-related molecules. In addition, the expression of PTEN, a miR-21 target gene, was inhibited and Akt signaling was activated in the procedure. Taken together, these data indicate that miR-21 could be a potential therapeutic target for interventions after TBI.
Subject(s)
Brain Injuries/genetics , MicroRNAs/genetics , Animals , Apoptosis/genetics , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Astrocytes/metabolism , Brain Injuries/metabolism , Brain Injuries/pathology , Brain Injuries/physiopathology , Disease Models, Animal , Gene Expression , Immunohistochemistry , Male , MicroRNAs/metabolism , Microglia/metabolism , Neovascularization, Physiologic/genetics , Neurons/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Signal TransductionABSTRACT
Two new metabolites, an α-pyridone derivative, 3-hydroxy-2-methoxy-5-methylpyridin-2(1H)-one (1), and a ceramide derivative, 3-hydroxy-N-(1-hydroxy-3-methylpentan-2-yl)-5-oxohexanamide (2), and a new natural product, 3-hydroxy-N-(1-hydroxy-4-methylpentan-2-yl)-5-oxohexanamide (3), along with 15 known compounds including chaetoglobosin C (7) and chaetoglobosin F (8) were isolated from the solid culture of the endophytic fungus Botryosphaeria dothidea KJ-1, collected from the stems of white cedar (Melia azedarach L). The structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR experiments and by mass spectrometric measurements), and the structure of 1 was confirmed by X-ray single-crystal diffraction. These metabolites were evaluated in vitro for antimicrobial, antioxidant, and cytotoxicity activities. Pycnophorin (4) significantly inhibited the growth of Bacillus subtilis and Staphyloccocus aureus with equal minimum inhibitory concentration (MIC) values of 25 µM. Stemphyperylenol (5) displayed a potent antifungal activity against the plant pathogen Alternaria solani with MIC of 1.57 µM comparable to the commonly used fungicide carbendazim. Both altenusin (9) and djalonensone (10) showed markedly DPPH radical scavenging activities. In addition, stemphyperylenol (5) and altenuene (6) exhibited strong cytotoxicity against HCT116 cancer cell line with a median inhibitory concentration (IC50) value of 3.13 µM in comparison with the positive control etoposide (IC50 = 2.13 µM). This is the first report of the isolation of these compounds from the endophytic B. dothidea.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Ascomycota/chemistry , Cytotoxins/pharmacology , Endophytes/chemistry , Fungicides, Industrial/pharmacology , Melia azedarach/microbiology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Antioxidants/chemistry , Antioxidants/metabolism , Ascomycota/metabolism , Bacteria/drug effects , Cell Line, Tumor , Cytotoxins/chemistry , Cytotoxins/metabolism , Endophytes/metabolism , Fungi/drug effects , Fungicides, Industrial/chemistry , Fungicides, Industrial/metabolism , Humans , Microbial Sensitivity Tests , Secondary MetabolismABSTRACT
In preceding studies, cultivation of Chaetomium globosum, an endophytic fungus in Ginkgo biloba, produced five cytochalasan mycotoxins, chaetoglobosins A, G, V, Vb, and C (1-5), in three media. In the present work, five known chaetoglobosins, C, E, F, Fex, and 20-dihydrochaetoglobosin A (5-9), together with the four known compounds (11-14), were isolated from the MeOH extracts of the solid culture of the same endophyte. The structures of these metabolites were elucidated on the basis of spectroscopic analysis. Treatment of chaetoglobosin F (7) with (diethylamino)sulfur trifluoride (DAST) in dichloromethane afforded an unexpected fluorinated chaetoglobosin, named chaetoglobosin Fa (10), containing an oxolane ring between C-20 and C-23. The phytotoxic effects of compounds 1, 3-8, and 10 were assayed on radish seedlings; some of these compounds (1, 3, and 6-8) significantly inhibited the growth of radish (Raphanus sativus) seedlings with inhibitory rates of >60% at a concentration of 50 ppm, which was comparable or superior to the positive control, glyphosate. In addition, the cytotoxic activities against HCT116 human colon cancer cells were also tested, and compounds 1 and 8-10 showed remarkable cytotoxicity with IC50 values ranging from 3.15 to 8.44 µM, in comparison to the positive drug etoposide (IC50 = 2.13 µM). The epoxide ring between C-6 and C-7 or the double bond at C-6(12) led to a drastically increased cytotoxicity, and chaetoglobosin Fa (10) displayed a markedly increased cytotoxicity but decreased phytotoxicity.
Subject(s)
Chaetomium/metabolism , Cytotoxins/toxicity , Endophytes/metabolism , Ginkgo biloba/microbiology , Indole Alkaloids/metabolism , Indole Alkaloids/toxicity , Mycotoxins/metabolism , Mycotoxins/toxicity , Raphanus/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chaetomium/chemistry , Cytotoxins/metabolism , Endophytes/chemistry , Humans , Raphanus/growth & developmentABSTRACT
On the basis of the OSMAC (one strain-many compounds) strategy, 14 indole diketopiperazine (DKP) alkaloids, including spirotryprostatins (1-3), tryprostatins (4-6), and cyclotryprostatins (7-14), were isolated from the endophyte Aspergillus fumigatus associated with Melia azedarach L. Their structures were identified by nuclear magnetic resonance and electrospray ionization mass spectrometry data. All the indole DKPs were evaluated for plant growth regulation using the lettuce (Lactuca sativa) seedling growth bioassay, which showed the plant growth influence of the seedling. Among these compounds tested, a tryprostatin-type compound, brevianamide F (6), was identified as a new type of natural potential plant growth inhibitor with a response index (RI) higher than that of the positive control glyphosate, a broad-spectrum systemic herbicide. 6 can also inhibit turnip (Raphanus sativus) shoot and root elongation with RIs of -0.76 and -0.70, respectively, at 120 ppm, and it strongly inhibits amaranth (Amaranthus mangostanus) seedling growth with a high RI of -0.9 at 40 ppm. The structure-allelopathic activity relationship analysis of these isolated alkaloids indicates that tryprostatin-type alkaloids without the C5 prenyl and methoxy group give the most potent inhibition of seedling growth. Brevianamide F (6) could be used to develop a natural eco-friendly herbicide.
Subject(s)
Aspergillus fumigatus/chemistry , Diketopiperazines/pharmacology , Herbicides/pharmacology , Amaranthus/drug effects , Chromatography, High Pressure Liquid , Diketopiperazines/chemistry , Endophytes/chemistry , Germination/drug effects , Herbicides/chemistry , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Indoles/chemistry , Indoles/pharmacology , Lactuca/drug effects , Lactuca/growth & development , Magnetic Resonance Spectroscopy , Melia/microbiology , Molecular Structure , Plant Growth Regulators/pharmacology , Raphanus/drug effects , Seedlings/drug effects , Spectrometry, Mass, Electrospray Ionization , Structure-Activity RelationshipABSTRACT
The title compound, C(10)H(13)ClN(2)O, was obtained as a by-product in the reaction of 2-chloro-methyl-1H-benzimidazole, dimethyl sulfate and toluene to synthesise 2-chloro-methyl-1-methyl-benzimidazole. The dihedral angle between the benzene ring and the acetamide group is 89.72 â (6)° while that between the aromatic ring and the chloracetyl group is 84.40â (4)°. In the crystal, adjacent mol-ecules are linked by pairs of N-Hâ¯O hydrogen bonds into inversion dimers.
ABSTRACT
A series of 35 benzimidazole derivatives were synthesized from 2-chloromethyl-1H-benzimidazole in good yields. Their structures were characterized by (1)H and (13)C NMR and HRESIMS. Antifungal activities of all of the synthesized compounds were evaluated against five phytopathogens fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Compound 4m displayed strong growth inhibition of C. gloeosporioides, A. solani, and F. solani with IC50 of 20.76, 27.58, and 18.60 µg/mL, respectively. Selective inhibition of B. cinerea instead of the other fungal pathogenes was observed with 7f (IC50 of 13.36 µg/mL), comparable to that of positive control, a commercial agricultural fungicide hymexazol (IC50 of 8.92 µg/mL). Compound 5b exhibited remarkable antifungal properties against Cytospora sp., C. gloeosporioides, B. cinerea, and F. solani with IC50 values of 30.97, 11.38, 57.71, and 40.15 µg/mL, respectively; among the target fungi, 5b was the most active compound and superior to the reference against C. gloeosporioides alone. Structure-activity relationship (SAR) data of these compounds are as follows: (1) introduction of the chlorine atom on para-position in the benzene ring help to increase activity (4f vs 4c; 7f vs 7n), (2) the sulfonyl group is critical for the inhibition of C. gloeosporioides (5b and 5c vs 5a), and (3) the unsubstituted benzene ring improve activity (4m vs 4n, 4e and 4a). Thus, compounds 5b, 4m, and 7f emerged as a new leading structure for the development of new fungicides.
Subject(s)
Benzimidazoles/pharmacology , Fungi/drug effects , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/pharmacology , Plant Diseases/microbiology , Benzimidazoles/chemistry , Fungi/growth & development , Fungi/physiology , Fungicides, Industrial/chemistry , Molecular Structure , Structure-Activity RelationshipABSTRACT
Several series of 45 acetophenone derivatives bearing various alkyl or benzyl substituents were conveniently synthesized and their structures characterized by (1)H and (13)C NMR spectroscopy, HRMS and single-crystal X-ray analysis. Their in vitro antifungal activities against a panel of phytopathogenic fungi were evaluated by mycelial growth rate assay. Of them, 12 derivatives (e.g., 3a-c, 4c and 4e) exhibited more potent antifungal effects on some phytopathogens than a commercial fungicide hymexazol as positive control. In particular, compound 3b with IC50 values of 10-19 µg/mL was found to be the most active in this series and might be a potential lead structure for further optimization. The preliminary structure-activity relationship (SAR) studies of a series of acetophenones are also discussed.
Subject(s)
Acetophenones/chemistry , Antifungal Agents/chemistry , Biological Products/chemistry , Acetophenones/chemical synthesis , Acetophenones/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Biological Products/isolation & purification , Biological Products/pharmacology , Fungi/drug effects , Microbial Sensitivity Tests , Oxazoles/pharmacology , Structure-Activity RelationshipABSTRACT
Nine secondary metabolites, including four steroids, four phenolics and one cerebroside, were isolated from the methanol extract of the fruiting bodies of the basidiomycete Sarcodon joedes. The isolated compounds were identified by spectroscopic analyses as (22E,24R)-6ß-methoxyergosta-7,22-diene-3ß,5α-diol (1), 2',3'-diacetoxy-3,4,5',6',4â³-pentahydroxy-p-terphenyl (2), cerebroside B (3), ergosta-7,22-dien-3ß-ol (4), ergosterol peroxide (5), (22E,24R)-3ß-hydroxy-ergosta-5,22-dien-7-one (6), benzoic acid (7), methyl p-hydroxybenzoate (8) and 3,4-dihydroxybenzoic acid (9). The cytotoxic activities of these compounds were evaluated. All these compounds were isolated from this fungus for the first time.