4-Aminoquinolines Bearing a 1,3-Benzodioxole Moiety: Synthesis and Biological Evaluation as Potential Antifungal Agents

In search of new environmentally friendly and effective antifungal agents, a series of 4-aminoquinolines bearing a 1,3-benzodioxole moiety were prepared and their structures were fully elucidated by spectroscopic analyses. The antifungal activities of all the target compounds against five phytopathogenic fungi were evaluated in vitro. The results revealed that most of the newly synthesized compounds exhibited obvious inhibitory activities at the concentration of 50 μg/mL. Among them, 6-(furan-2-yl)-N-(4-methylphenyl)-2H-[1,3]dioxolo[4,5-g]quinolin-8-amine hydrochloride ( 7m ) displayed more promising antifungal potency with EC₅₀ values of 10.3 and 14.0 μg/mL against C. lunata and A. alternate, respectively. Particularly, the EC₅₀ value of 7m against C. lunata was 7.3-fold as potent as the standard azoxystrobin. There were some significant morphological alterations in the mycelia of C. lunata when treated with 7m at 50 μg/mL. Additionally, the preliminary structure–activity relationships (SARs) were also discussed. Thus, this study suggests that 4-aminoquinolines bearing a 1,3-benzodioxole moiety are interesting scaffolds for the development of novel antifungal agents.     

Discovery of benzotriazole-azo-phenol/aniline derivatives as antifungal agents

A series of benzotriazole-azo-phenol/aniline derivatives were prepared and evaluated for their antifungal activities against six phytopathogenic fungi such as Fusarium graminearum, Fusarium solani, Alternaria alternate, Valsa mali, Botrytis cinerea, and Curvularia lunata. Among them, compounds IIf, IIn, and IIr showed a broad-spectrum of potent antifungal activities. Especially some compounds displayed 3.5–10.8 folds more potent activities than carbendazim against A. alternata and C. lunata. Notably, compounds IIc, IIm, and IIr exhibited good protective and therapeutic effects against B. cinerea at 200?μg/mL. Their structure-activity relationships were also discussed.     

Design,Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs

In search for SDHIs fungicides, twenty-five novel carboxamides containing a chalcone scaffold were designed, synthesized, and evaluated for antifungal activities against five pathogenic fungi. The results showed that compound 5 k exhibited outstanding antifungal activity against R. solani with an EC₅₀ value of 0.20 μg/mL, which was much better than that of commercial SDHIs Boscalid (EC₅₀=0.74 μg/mL). Moreover, compound 5 k also displayed promising antifungal activities against S. sclerotiorum, B. cinerea, and A. alternate (IC₅₀=2.53–4.06 μg/mL), indicating that 5 k had broad-spectrum antifungal activity. Additionally, in vivo antifungal activities results showed that 5 k could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (57.78 %) and curative efficacy (58.45 %) at 100 μg/mL, both of which were much better than those of Boscalid, indicating a promising application prospect. Moreover, SEM analysis showed that compound 5 k could remarkably disrupt the typical structure and morphology of R. solani hyphae. Further SDH enzyme inhibition assay and molecular docking study revealed that lead compound 5 k had a similar mechanism of action as commercial SDHI Boscalid. These results indicated that compound 5 k showed potential as a SDHIs fungicide and deserved further investigation.     

Cyclohexenone Derivative and Drimane Sesquiterpenes from the Seagrass-Derived Fungus Aspergillus insuetus

One new cyclohexenone derivative ( 1 ), and two undescribed drimane sesquiterpenes ( 2 and 3 ), together with another seven known drimane sesquiterpenes were isolated from a seagrass-derived fungus Aspergillus insuetus SYSU6925. Structures of these metabolites were elucidated by comprehensive spectroscopic analysis, including NMR analysis, mass spectrometry, and ECD calculations. Compounds 1 – 3 , 5 and 7 displayed weak to moderate antifungal activities towards four phytopathogenic fungi, with Minimum inhibition concentration (MIC) values range from 50 to 200 μg/mL. Compound 1 , a rare cyclohexenone derivative with n-propyl group exhibited more potent inhibitory activities (MIC, 50 μg/mL) against F. oxysporum than positive control (Triadimefon). Compounds 2 and 3 also exhibit potent anti-inflammatory activities by inhibiting the production of nitric oxide (NO) in RAW264.7 cells with IC₅₀ values of 21.5±1.1 and 32.6±1.16 μM, respectively.     

Novel N‐Cycloalkylcarbonyl‐N′‐arylthioureas: Synthesis,Design, Antifungal Activity and Gene Toxicity

A synthesis method of novel N‐cycloalkylcarbonyl‐N′‐arylthioureas was developed. It consists of sequential addition of equimolecular amounts of ammonium isothiocyanate and substituted anilines to cycloalkylcarbonyl chlorides. The identity and purity of products were confirmed by LC/MS spectra, their structure by elemental analysis, IR and ¹H‐NMR spectra. Preliminary antimicrobial screening for standard microorganisms and molecular docking allowed to select several structures for antifungal and genetic toxicity studies. Conducted in vitro screening of 9 compounds for antifungal potential against 11 phytopathogenic fungi and three Phytophthora strains revealed that two N‐(arylcarbamothioyl) cyclopropanecarboxamides at a concentration of 50 μg/ml exhibited activities comparable to the standard antifungal agent ‘Cyproconazole’. Analysis of mutagenicity of novel thioureas using the Salmonella reverse mutagenicity assay (‘Ames Test’) showed a low gene‐toxicity profile.     

黄花倒水莲内生真菌生物活性评价及HNLF-44菌株鉴定

为充分开发黄花倒水莲(Polygala fallax)的内生真菌资源，获得具有抗植物病原真菌、抗氧化活性的内生真菌，该文以黄花倒水莲内生真菌为研究对象，使用平板对峙法检测内生真菌对6种植物病原真菌的抑菌活性，测定内生真菌发酵液的DPPH清除自由基能力和总还原能力，评价内生真菌的抗氧化活性，并对具有强抑菌活性和抗氧化活性的菌株进行形态和ITS鉴定。结果表明：(1)黄花倒水莲内生真菌中有2株内生真菌对香蕉专化尖孢镰刀菌、柑橘树脂病菌、叶点霉菌、香蕉具条叶斑病菌、茄病镰刀菌、三七根腐病菌具有明显的抑菌活性，抑菌率在50.3%～91.4%之间，其中HNLF-5对柑橘树脂病菌的抑菌率为73.2%,HNLF-44对香蕉专化尖孢镰刀菌抑菌率为91.4%。(2)内生真菌发酵液具有良好的抗氧化活性，DPPH清除率均在80%以上，总还原能力吸光值范围为0.279 2～0.748 8。(3)HNLF-44菌株为链格孢属真菌。该研究表明，药用植物黄花倒水莲内生真菌具有较好的生物活性，为后续从黄花倒水莲内生真菌中挖掘潜在新型抑菌活性和抗氧化活性物质奠定了基础。     

Design,synthesis and antifungal activity of amide and imine derivatives containing a kakuol moiety

In continuation of our program to discover new potential antifungal agents, a series of amide and imine derivatives containing a kakuol moiety were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against four plant pathogenic fungi, and structure–activity relationships (SAR) were derived. Compounds 7d, 7e, 7h, 7i and 7r showed obvious inhibitory activity against the corresponding tested fungi at 50 μg/mL. Especially, compounds 7e and 7r displayed more potent antifungal activity against B. cinerea than that of thiabendazole (a positive control). Moreover, compound 7e also exhibited good activity against A. alternata with EC₅₀ values of 11.0 µg/mL, and the value was slightly superior to that of thiabendazole (EC₅₀ = 14.9 µg/mL). SAR analysis showed that the ether group was a highly sensitive structural moiety to the activity and the type as well as position of substituents on benzene ring could make some effects on the activity.     

Synthesis and antifungal activity of imidazo[1,2-b]pyridazine derivatives against phytopathogenic fungi

A series of 3,6-disubstituted imidazo[1,2-b]pyridazine derivatives have been synthesized and characterized with spectroscopic analyses. The antifungal activities of these compounds against nine phytopathogenic fungi were evaluated by the mycelium growth rate method. The in vitro antifungal bioassays indicated that most of compounds displayed excellent and broad-spectrum antifungal activities. Especially, compounds 4a, 4c, 4d, 4l and 4r exhibited 1.9–25.5 fold more potent than the commercially available fungicide hymexazol against Corn Curvalaria Leaf Spot (CL), Alternaria alternate (AA), Pyricularia oryzae (PO) and Alternaria brassicae (AB) strains. Structure-activity relationship analysis showed that the enhanced antifungal activity is significantly affected by the substituents on the benzene ring and pyridazine ring.     

Design,Synthesis, and Antifungal Activities of Novel 1,2,4‐Triazole Schiff Base Derivatives

With the aim to find new compounds with high antifungal activity, 21 4‐amino‐5‐substituted‐1,2,4‐triazole Schiff bases ( 2a  –  2g , 3a  –  3g , and 4a  –  4g ) were designed and synthesized. Their antifungal activities against Pythium solani, Gibberlla nicotiancola, Fusarium oxysporium f. sp. niveum, Gibberlla saubinetii, Alternaria iycopersici, Phytophthora capsici, Physalospora piricola, Cercospora arachidicola hori, and Fusarium oxysporium f. sp. cucumber were tested, parts of the compounds exhibited excellent antifungal activity. This research provides useful information for further study of antifungal agents.     

Antifungal Activity and Action Mechanism Study of Coumarins from Cnidium monnieri Fruit and Structurally Related Compounds

The increasing resistance of plant diseases caused by phytopathogenic fungi highlights the need for highly effective and environmentally benign agents. The antifungal activities of Cnidium monnieri fruit extracts and five isolated compounds as well as structurally related coumarins against five plant pathogenic fungi were evaluated. The acetone extract, which contained the highest amount of five coumarins, showed strongest antifungal activity. Among the coumarin compounds, we found that 4-methoxycoumarin exhibited stronger and broader antifungal activity against five phytopathogenic fungi, and was more potent than osthol. Especially, it could significantly inhibit the growth of Rhizoctonia solani mycelium with an EC₅₀ value of 21 μg mL⁻¹. Further studies showed that 4-methoxycoumarin affected the structure and function of peroxisomes, inhibited the β-oxidation of fatty acids, decreased the production of ATP and acetyl coenzyme A, and then accumulated ROS by damaging MMP and the mitochondrial function to cause the cell death of R. solani mycelia. 4-Methoxycoumarin presented antifungal efficacy in a concentration- dependent manner in vivo and could be used to prevent the potato black scurf. This study laid the foundation for the future development of 4-methoxycournamin as an alternative and friendly biofungicide.     

Antifungal activity of six Saudi medicinal plant extracts against five phyopathogenic fungi

Six medicinal plants such as Amaranthus spinosus, Barbeya oleoides, Clutia lanceolata, Lavandula pubescens, Maerua oblongifolia and Withania somnifera collected from different locations in the southwestern part of Saudi Arabia were tested for antifungal activities against five plant pathogenic fungi causing serious diseases of vegetable crops. These fungi were Alternaria brassicae, Alternaria solani, Botrytis fabae, Fusarium solani and Phytophthora infestans. Aqueous plant extracts reduced mycelial growth and inhibited spore germination of all fungi tested. It is clear that the aqueous extract of Lavandula pubescens leaves was the best for controlling all phytopathogenic fungi under study. These results suggested that medicinal plant extracts play an important role in controlling the phytopathogenic fungi.     

Antifungal Activity of Cadinane-Type Sesquiterpenes from Eupatorium adenophorum against Wood-Decaying Fungi

The present study aimed to evaluate the antifungal activities of Eupatorium adenophorum against four strains of wood-decaying fungi, including Inonotus hispida, Inonotus obliquus, and Inonotus cuticularis. Bioguided isolation of the methanol extract of E. adenophorum by silica gel column chromatography and high-performance liquid chromatography afforded six cadinane-type sesquiterpenes. Their structures were identified by nuclear magnetic resonance and MS analyses. According to the antifungal results, the inhibition rate of the compound was between 59.85 % and 77.98 % at a concentration of 200 μg/mL. The EC₅₀ values ranged from 74.5 to 187.4 μg/mL.     

Screening biological activities of soil-borne Streptomyces sp. against several phytopathogenic fungi

About 70 Streptomyces species, isolated from soils of greenhouses and citrus orchards were evaluated for their antagonistic activity against Verticillium dahliae, Fusarium subglutinans, Fusarium sambucinum, Phoma glomerata and Nattrassia mangiferae. Preliminary screening for antimicrobial activity was determined by dual culture method. The soils of Kerman are rich sources of micro-organisms with potent biological activities, and screening programmes are to be conducted to reveal the presence of active Actinomycetes isolates against phytopathogenic fungi.     

11种植物精油对6种植物病原真菌的抑菌活性研究

为筛选有效的植物杀菌成分,采用菌丝生长法,测定了香茅油、薰衣草油、菊花油、月桂油、柠檬油、广藿香油、肉桂油、天竺葵油、迷迭香油、茶树油、薄荷油对6种植物病原真菌的抑菌活性。发现在2 g/L的浓度下,上述11种精油对6种供试病菌均有明显的抑制作用,其中香茅油、肉桂油、天竺葵油、月桂油、茶树油和薄荷油对6种病原真菌的抑制率均为100%。剂量效应试验表明,肉桂油对灰葡萄孢（Botrytis cinerea）和禾谷镰孢菌（Fusariumgraminearum）的EC50值分别为29.05μg/mL和42.96μg/mL,而天竺葵油对灰葡萄孢（Botrytis cinerea）和禾谷镰孢菌（Fusarium graminearum）的EC50值分别为34.02μg/mL和68.48μg/mL。     

Antifungal Activities of N-Arylbenzenesulfonamides against Phytopathogens and Control Efficacy on Wheat Leaf Rust and Cabbage Club Root Diseases

A set of N-arylbenzenesulfonamides with various substituents at the arylamine and benzenesulfonyl positions were prepared, and their antifungal properties were measured in vitro against such plant pathogenic fungi as Pythium ultimum, Phytophthora capsici, Rhizoctonia solani, and Botrytis cinerea. Compounds 3, 4, 8, 9, 10, 14, 16, 18, 20, 21, 24 and 27 had antifungal activity over a broad spectrum of the phytopathogenic fungi tested, where 50% of inhibition (ED₅₀) was in the range of 3-15 μg/ml. Based on the in vitro activity, six derivatives (3, 4, 10, 18, 21 and 27) were selected and tested further for their fungicidal efficacy in vivo. The fungicidal efficacy of 10, 21 and 27 had a disease control value of over 85% at 50 μg/ml against wheat leaf rust, while that of 4 was selective against cabbage club root disease.     

Prenylated flavonoids and total extracts from Morus nigra L. root bark inhibit in vitro growth of plant pathogenic fungi

Total extracts and kuwanon G from Morus nigra root bark showed antifungal activity against several phytopathogenic fungi, with minimal inhibitory concentration (MIC₅₀) ranging from 32 to 128 μg/ml and from 16 to 64 μg/ml, respectively. Acetonic extracts inhibited 60% B. cinerea biofilm formation at concentration of 128 μg/ml.     

天山大峡谷原始森林黏细菌的分离鉴定及其抗菌活性

【背景】黏细菌是一类具有多细胞群体行为特征的高等原核生物,其对植物病原真菌和细菌的捕食特性使其在植物病害防治方面具有重要的应用潜力。【目的】探究乌鲁木齐天山大峡谷原始森林可培养黏细菌的多样性并分析其抗菌活性,为发掘黏细菌生防菌株奠定基础。【方法】以天山大峡谷原始森林采集的土样和腐木为分离材料,采用兔粪诱导法和被捕食菌诱导法从中分离纯化黏细菌菌株,结合形态学观察、生理生化测定和16S rRNA基因序列分析确定其分类地位,并以6种植物病原真菌[大丽轮枝菌(Verticillium dahliae)、尖孢镰刀菌萎蔫专化型(Fusarium oxysporum f. sp. vasinfectum)、拟轮枝链孢霉(Fusarium verticillioides)、立枯丝核菌(Rhizoctonia solani)、黄色镰刀菌(Fusarium culmorum)、细极链格孢菌(Alternaria tenuissima)]和1种植物病原细菌[梨火疫病菌(Erwinia amylovora)]为靶标菌,通过平板对峙法和菌苔捕食法测定其抗菌活性。【结果】从采集的样品中分离出70株菌株,经纯化后获得36株黏细菌纯培养物。经鉴定隶属于4个属,黏球菌属(Myxococcus) 30株、孢囊杆菌属(Cystobacter) 3株、珊瑚球菌属(Corallococcus) 2株和原囊菌属(Archangium) 1株。抗菌活性分析显示,本研究获得的36株黏细菌至少对2种植物病原真菌有抗菌活性,表现出广谱的抗真菌活性,初步筛选出一株菌株NSE37-1兼具广谱和高效抗真菌活性;供试的15株黏细菌对梨火疫病菌均具有捕食活性,初步筛选出一株对梨火疫病菌具有较强捕食能力的黏细菌菌株NSE25。【结论】天山大峡谷可培养黏细菌资源比较丰富,黏球菌属是该地区可培养黏细菌菌群中的优势菌。分离纯化出的黏细菌菌株均表现出广谱的抗植物病原菌活性,具有进一步研究和开发的潜在价值。     

Synthesis and bioactivities of novel thioether/sulfone derivatives containing 1,2,3-thiadiazole and 1,3,4-oxadiazole/thiadiazole moiety

A series of new thioether/sulfone compounds containing 1,2,3-thiadiazole and 1,3,4-oxadiazole/1,3,4-thiadiazole moiety were synthesized, the structures of all products were confirmed by IR, ¹H NMR, ¹³C NMR, and element analysis. Preliminary antifungal activity test showed that compound 8a exhibited moderate antifungal activity against Fusarium oxysporum at 50 μg/mL. Preliminary antiviral activity results showed that compounds 7a, 7c, 7d, 8a, and 9a displayed high antiviral activity against tobacco mosaic virus. The present work demonstrates that thioether/sulfone heterocyclic derivatives could be considered as new lead compounds for antiviral studies.     

Antifungal agents. Part 5: synthesis and antifungal activities of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles

In order to discover more promising antifungal agents, a series of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles (5a-r) were prepared and evaluated in vitro for their antifungal activities against seven phytopathogenic fungi. Especially compounds 5n and 5o exhibited more potent antifungal activities than or comparable to hymexazol, a commercially available agricultural fungicide at the concentration of 100 μg/mL. Preliminary structure-activity relationships study demonstrated that introduction of electron-donating substituents R(1) and R(2), and the proper length of substituent R(3) were usually very important for their antifungal activities.     

Antibacterial activity of hinokitiol against both antibiotic‐resistant and ‐susceptible pathogenic bacteria that predominate in the oral cavity and upper airways

Hinokitiol, a component of the essential oil isolated from Cupressaceae, possesses antibacterial and antifungal activities and has been used in oral care products. In this study, the antibacterial activities of hinokitiol toward various oral, nasal and nasopharyngeal pathogenic bacteria, including Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, methicillin‐resistant and ‐susceptible Staphylococcus aureus, antibiotic‐resistant and ‐susceptible Streptococcus pneumoniae, and Streptococcus pyogenes were examined. Growth of all these bacterial strains was significantly inhibited by hinokitiol, minimal inhibitory concentrations of hinokitiol against S. mutans, S. sobrinus, P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, methicillin‐resistant S. aureus, methicillin‐susceptible S. aureus, antibiotic‐resistant S. pneumoniae isolates, antibiotic‐susceptible S. pneumoniae, and S. pyogenes being 0.3, 1.0, 1.0, 30, 0.5, 50, 50, 30, 0.3–1.0, 0.5, and 0.3 μg/mL, respectively. Additionally, with the exception of P. gingivalis, hinokitiol exerted bactericidal effects against all bacterial strains 1 hr after exposure. Hinokitiol did not display any significant cytotoxicity toward the human gingival epithelial cell line Ca9‐22, pharyngeal epithelial cell line Detroit 562, human umbilical vein endothelial cells, or human gingival fibroblasts, with the exception of treatment with 500 μg/mL hinokitiol, which decreased numbers of viable Ca9‐22 cells and gingival fibroblasts by 13% and 12%, respectively. These results suggest that hinokitiol exhibits antibacterial activity against a broad spectrum of pathogenic bacteria and has low cytotoxicity towards human epithelial cells.