Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents

A new series of 2-arylquinoline-4-carboxylic acid hydrazide–hydrazones was synthesized using an appropriate synthetic route. All the target compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram-positive bacteria, Escherichia coli as an example for Gram-negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the compounds tested, compounds having nitro substituents at the arylidene moiety showed the most potent antifungal as well as antibacterial activities against E. coli. Compound 23 displayed an antifungal activity comparable to that of nystatin. However, none of the compounds demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 μg/mL. In addition, the most potent compound (23) was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells.     

The influence of molecular weight of quaternized chitosan on antifungal activity

Quaternized chitosan derivatives with different molecular weights were synthesized in the laboratory. Subsequent experiments were conducted to test their antifungal activities against Botrytis cinerea Pers. (B. cinerea pers.) and Colletotrichum lagenarium (Pass) Ell.et halst (C. lagenarium (Pass) Ell.et halst). Our results indicate that quaternized chitosan derivatives have stronger antifungal activities than chitosan. Furthermore, quaternized chitosan derivatives with high molecular weight are shown to have even stronger antifungal activities than those with low molecular weight.     

Activity of dehydroabietic acid derivatives against wood contaminant fungi

The antifungal activity of 10 dehydroabietic acid derivatives with different configuration in A and B rings (cis/trans A/B junction) and different substituents and/or functionalities was evaluated in bioassays in vitro and in situ (pine wood blocks).

The test compounds dissolved in acetone were assayed at several concentrations w/w (test compound/culture medium) against the fungi. The Relative Inhibition (RI) was determined by measuring the radial growth of colonies of the fungi treated with the test compounds by comparison with those of control cultures; the results are expressed as EC₅₀.

The results of bioassays in vitro have shown that hydroxyl and aldehyde functions are required for antifungal activity in this group of compounds and deisopropylation can increase the activity. Our assay of antifungal activity in situ (in pine wood blocks) provides a means to investigate the preservative activities of these antifungal compounds under actual conditions of use.

The dehydroabietic acid derivative cis-deisopropyldehydroabietanol (10) inhibited the growth of several of the fungi tested, in vitro and in situ.

The results obtained in situ with the test compound (10) at 6% and 8% were not significantly different from the reference products and a good level of protection of the wood against the organisms tested was achieved.

The results in wood bioassays present new possibilities in the search for natural new compounds in the wood protection, as an alternative to conventional fungicides.     

Synthesis of 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine derivatives as antimicrobial agents

A series of novel substituted 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine benzamides 9(a–h) were synthesized to determine their antibacterial and antifungal activities as well as possible structure–activity relationships (SARs) to improve therapeutic efficacy. The pyrazol-5-amine benzamides were screened for their antibacterial activity against standard strains of Gram-positive (Streptococcus pyogenes NCIM 2608, Staphylococcus aureus ATCC 29737, Bacillus subtilis NCIM 2010) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 20852, Klebsiella pneumoniae MTCC 618) bacteria by using streptomycin as positive control. They were also tested for their antifungal activities against mycotoxic strains of Fusarium verticillioides, Aspergillus ochraceous, Aspergillus flavus, Alternaria alternata, and Penicillium chrysogenum using nystatin as positive control. Among the synthesized compounds, 9d, 9g, and 9h showed potent antimicrobial activities.     

蝉虫草（蝉花）来源的化合物鉴定与抗菌活性检测

蝉虫草（蝉花）是我国重要的传统中药材之一,用于治疗慢性肾炎等,但对其活性成分的研究仍不充分。本文采用硅胶柱、凝胶柱、ODS柱分离,以及HPLC等色谱技术,对蝉虫草子实体样品的乙酸乙酯提取物进行分离纯化,得到3个化合物。根据波谱学数据,化合物1-3分别鉴定为(E,E)-9-酮-10,12-十八碳二烯酸(E,E)-9-oxooctadeca-10,12-dienoic acid（1）、麦角甾醇ergosterol（2）和白僵菌酮bassiatin（3）,其中化合物1为首次从蝉虫草中分离获得。抑菌实验表明,3个化合物均对革兰氏阴性大肠杆菌Escherichia coli和革兰氏阳性枯草芽孢杆菌Bacillus subtilis有显著的抑菌活性,化合物1和3还对条件致病真菌白色念珠菌Candida albicans有明显的抑菌活性。本文的研究结果丰富了蝉虫草的活性化合物组成。     

芳樟醇对灰葡萄孢生长的影响及对番茄灰霉病的防控效果

通过平板抑菌试验和孢子萌发试验研究了芳樟醇对灰葡萄孢的生长抑制作用,并通过盆栽试验进一步验证了芳樟醇对番茄灰霉病的防控效果。结果表明: 芳樟醇能够显著抑制灰葡萄孢菌丝的生长,半最大效应浓度(EC₅₀)值为0.581 mL·L^-1。孢子萌发试验中,芳樟醇能够有效抑制灰葡萄孢孢子的萌发,并表现出浓度依赖性。芳樟醇处理提高了灰葡萄孢菌菌丝体的相对电导率和丙二醛(MDA)含量,说明芳樟醇可引起氧化损伤效应导致灰葡萄孢菌的膜系统被破坏;芳樟醇处理后灰葡萄孢菌中的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、过氧化物酶(POD)活性较对照组分别下降了27.4%、68.9%和26.0%,说明芳樟醇抑制了灰葡萄孢菌体内的抗氧化系统。盆栽试验结果显示,芳樟醇处理的病斑直径较对照组显著降低;番茄叶片中的SOD、CAT、POD、多酚氧化酶和苯丙氨酸解氨酶活性均显著高于对照组;而MDA含量下降了41.5%,说明芳樟醇可减轻灰葡萄孢菌对番茄植株造成的氧化损伤以提高植物抗病性。综上,芳樟醇对灰葡萄孢的生长有显著抑制作用并对番茄灰霉病有较好的防治效果,研究结果可为开发新型植物源抑菌剂防控番茄灰霉病提供理论依据。     

Natural Product‐Based Fungicides Discovery: Design,Synthesis and Antifungal Activities of Some Sarisan Analogs Containing 1,3,4‐Oxadiazole Moieties

A series of sarisan analogs containing 1,3,4‐oxadiazole moieties were synthesized by iodine‐mediated oxidative cyclization and screened in vitro for their antifungal activities at 50 μg/mL against five phytopathogenic fungi such as Valsa mali, Curvularia lunata, Alternaria alternate, Fusarium solani and Fusarium graminearum. 1,3,4‐Oxadiazole derivatives 7e , 7p , 7r , 7t and 7u exhibited potent and a broad spectrum of antifungal activities against at least three phytopathogenic fungi at the concentration of 50 μg/mL. Especially, compound 7r displayed more potent antifungal activities against five phytopathogenic fungi than the positive control hymexazol. The EC₅₀ of 7r against V. mali, C. lunata and A. alternate were 12.6, 14.5 and 17.0 μg/mL, respectively. Additionally, some interesting results of structure‐activity relationships (SARs) were also observed.     

Effects of neolignans from the stem bark of Magnolia obovata on plant pathogenic fungi

Aims:  To characterize antifungal principles from the methanol extract of Magnolia obovata and to evaluate their antifungal activities against various plant pathogenic fungi.
Methods and Results:  Four neolignans were isolated from stem bark of M. obovata as antifungal principles and identified as magnolol, honokiol, 4-methoxyhonokiol and obovatol. In mycelial growth inhibition assay, both magnolol and honokiol displayed more potent antifungal activity than 4-methoxyhonokiol and obovatol. Both magnolol and honokiol showed similar in vivo antifungal spectrum against seven plant diseases tested; both compounds effectively suppressed the development of rice blast, tomato late blight, wheat leaf rust and red pepper anthracnose. 4-Methoxyhonokiol and obovatol were highly active to only rice blast and wheat leaf rust respectively.
Conclusions:  The extract of M. obovata and four neolignans had potent in vivo antifungal activities against plant pathogenic fungi.
Significance and Impact of the Study:  Neolignans from Magnolia spp. can be used and suggested as a novel antifungal lead compound for the development of new fungicide and directly as a natural fungicide for the control of plant diseases such as rice blast and wheat leaf rust.     

防风根际真菌的分离鉴定及其生防潜力评价

作为世界性分布的镰刀属常见病原真菌,尖孢镰刀菌（Fusarium oxysporum）和木贼镰刀菌（F. equiseti）对包括经济作物及药用植物等的生长均有较大危害。利用源自于植物根际土壤的有益微生物防控尖孢镰刀菌和木贼镰刀菌引起的真菌性病害,是目前较为理想的植物病害管理策略。为获得可有效抑制尖孢镰刀菌和木贼镰刀菌的生防菌源,于防风根际土壤中分离纯化真菌104株,基于平板对峙法筛选获得1株对尖孢镰刀菌和木贼镰刀菌具有显著抑制效果的菌株MR-43,结合形态特征、ITS序列分析,将其确定为Sirastachys castanedae（GenBank登录号：OK287148.1）,隶属于Sirastachys组进化分支,发现其可宿生于植物根际土壤。基于盆栽试验法,探究MR-43在防风栽培土壤中的定殖能力,评价MR-43对由尖孢镰刀菌引起的防风枯萎病和由木贼镰刀菌引起的防风根腐病的防病能力,及其对防风植株的促生能力。结果显示,Sirastachys castanedae MR-43对尖孢镰刀菌、木贼镰刀菌的抑菌率为57%以上,且经多次验证抑菌效果稳定;菌株MR-43可稳定定殖于防风栽培土壤并实现有效扩繁;菌株MR-43的孢子悬液可有效控制防风枯萎病和防风根腐病,平均防效达68.52%,与多菌灵、代森锰锌的防病效果无显著性差异（P>0.05）;此外,MR-43对防风植株生长具有明显促进作用。因此,Sirastachys castanedae MR-43在防风枯萎病、根腐病等真菌性病害管理方面具有较好的开发价值及应用潜力。     

Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiophen-4,9-quinones

Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote forms of Trypanosoma cruzi in vitro, (2) lysis of trypomastigote forms of T. cruzi in murine blood, (3) growth of Plasmodium falciparum in vitro, and (4) inhibition of the recombinant enzyme trypanothione reductase. The parent compound, naphtho[2,3-b]thiophen-4,9-quinone (3a), was among the most active quinone tested in vitro against P. falciparum at 0.2 μM. However, it was inactive against P. berghei-infected mice treated with 2.3 mmol/kg daily for 5 days. Most of the quinones prepared were active against T. cruzi epimastigotes in culture but exhibited weak activity at 4 °C against trypomastigotes in murine blood as well against the enzyme trypanothione reductase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.     

In vitro evaluation of antagonistic properties of Pseudomonas corrugata

Pseudomonas corrugata, a soil bacterium originally isolated from a temperate site of Indian Himalayan Region (IHR) is examined for its antagonistic activities against two phytopathogenic fungi, Alternaria alternata and Fusarium oxysporum. Although the bacterium did not show inhibition zones due to production of diffusible antifungal metabolites, a reduction in growth between 58% and 49% in both test fungi, A. alternata and F. oxysporum, was observed in sealed Petri plates after 120 h of incubation due to production of volatile antifungal metabolites. Reduction in biomass of A. alternata (93.8%) and F. oxysporum (76.9%) in Kings B broth was recorded after 48 h of incubation in dual culture. The antagonism was observed to be affected by growth medium, pH and temperature. The reduction in fungal biomass due to antagonism of bacteria was recorded maximum in the middle of the stationary phase after 21 h of inoculation. The production of siderophore, ammonia, lipase and chitinase in growth medium by P. corrugata were considered contributing to the antagonistic activities of the bacterium.     

毛筒壳科真菌次级代谢产物生物活性的评价

毛筒壳科Tubeufiaceae真菌具有产新结构、新活性次级代谢产物的潜力,目前对该科真菌次级代谢产物的研究较少。为了寻找具有生物活性的新化合物,有必要对毛筒壳科真菌次级代谢产物及其活性进行系统深入的研究。本文采用平板对峙法、生长速率法和MTT法,分别测定已分离得到的19株该科真菌活体菌株抑菌活性、发酵物抑菌活性以及发酵物粗提物对不同人体肿瘤细胞株增殖的抑制作用。通过平板对峙法,试验共筛选获得13株活性菌株,其中,红棕毛筒腔菌菌株Tubeufia rubra PF02-2对7种植物病原真菌有明显的抑菌效果,抑制率均高于60%且抑菌谱广。采用生长速率法,发现红棕毛筒腔菌菌株PF02-2经液体发酵后,发酵液对其中4种植物病原真菌仍有一定的抑制作用,且菌丝体部分的乙酸乙酯提取物对马铃薯早疫病病菌Alternaria solani（ZYB）的抑制效果最好。通过MTT法,发现发酵物粗提物对3种肿瘤细胞均具有不同程度的细胞毒活性,其中在300μg/mL时,剑叶莎毛筒腔菌菌株Tubeufia machaerinae ML03-2发酵液部分的乙酸乙酯提取物对人宫颈癌细胞株HeLa和人前列腺癌细胞株PC-3的抑制率（%）分别达到了98.92±0.15和97.86±0.18,在400μg/mL时,对人肝癌细胞株HEPG2的抑制率（%）达到了98.88±0.04;在500μg/mL时,明孢新旋卷孢菌菌株Neohelicosporium hyalosporum ML05-1菌丝体部分的乙酸乙酯提取物对人宫颈癌细胞株HeLa细胞的抑制率（%）为98.32±0.02,在600μg/mL时,对人肝癌细胞株HEPG2的抑制率（%）达到了97.62±0.20,在300μg/mL时,对人前列腺癌细胞株PC-3的抑制率（%）达到了98.91±0.02。该研究结果为开发利用毛筒壳科真菌提供了科学依据。     

Phenolics and antimicrobial activity of traditional stoned table olives 'alcaparra'

In the present work, we report the determination of phenolic compounds in ‘alcaparra’ table olives by reversed-phase HPLC/DAD, and the evaluation of their extract in vitro activity against several microorganisms that may be causal agents of human intestinal and respiratory tract infections, namely Gram positive (Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus), Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae) and fungi (Candida albicans and Cryptococcus neoformans). Three flavonoidic compounds were identified and quantified: luteolin 7-O-glucoside, apigenin 7-O-glucoside, and luteolin. At low concentrations (0.05 mg/mL) ‘alcaparra’ extract revealed significant inhibition of both Gram positive and Gram negative bacteria growth, with exception of P. aeruginosa. Nevertheless, no antifungal activity was observed at the tested concentrations.     

氯己定联合联苯苄唑对念珠菌的协同抗菌活性

本文用两种方法评价了联苯苄唑与氯己定联用对临床分离念珠菌的抑菌活性。微量液基稀释法显示,氯己定单独作用于念珠菌时,对念珠菌没有明显的抑制作用,最低抑菌浓度均大于16μg/mL;与联苯苄唑联合应用时,对17株念珠菌均表现为协同抑菌作用。纸片扩散法也观察到,含氯己定和联苯苄唑的纸片对4种念珠菌均能产生直径大于单药纸片的抑菌圈。结果显示,联苯苄唑联合低浓度氯己定对多种念珠菌具有协同抑菌作用。     

Enhancement in antimicrobial activity of 2-(phenyl)-3-(2-butyl-4-chloro-1H-imidazolyl)-5-butylate isoxazolidine

The trans rich isomer, 2-(phenyl)-3-(2-butyl-4-chloro-1H-imidazolyl)-5-butylate isoxazolidine A (>96% ee) was synthesized by the condensation of E isomer rich nitrone 4 (>98% ee) with butyl acrylate in an inert solvent. Obtained isoxazolidine was screened for its antifungal activity against Aspergillus niger, Cephalosporium acremonium, Fusarium moniliforme by using Nystatin as positive control. It was also tested for its antibacterial activity against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus by using Streptomycin as positive control. Enhanced antifungal activity was observed in isoxazolidine of >96% ee compared to the isoxazolidine of >69% ee (B), and enhancement was not observed in antibacterial activity.     

防治苦瓜枯萎病的拮抗放线菌分离筛选及鉴定

以苦瓜枯萎病菌为靶标菌,通过对峙培养试验和发酵滤液抑菌试验对分离自苦瓜根际土壤的放线菌进行筛选。候选菌株0250具有广谱抗真菌活性,根据培养特征、生理生化特性以及与同源性相近的菌株进行平均核苷酸一致性分析,被鉴定为Streptomyces rhizosphaericus,并评估了该菌株在温室和田间对苦瓜的促生长和防治枯萎病效果。结果表明: 链霉菌菌株0250对苦瓜枯萎病菌的平板抑制率为69.2%,对17种植物病原真菌的平板抑制率达64.3%~85.6%;该菌株的菌悬液处理能促进盆栽和田间苦瓜植株根、茎生长发育,提升产量,对苦瓜枯萎病的防病效果分别为66.9%和61.5%。预先用菌株0250菌悬液处理土壤再接种病原菌,对土壤尖镰孢菌数量抑制率达62.1%,显著提高了苦瓜幼苗苯丙氨酸解氨酶、过氧化物酶和β-1,3-葡聚糖酶活性以及根系活力。总之,菌株0250是一株对苦瓜枯萎病具有巨大生防潜力的放线菌资源。     

Synthetic, spectroscopic, biological and X-ray crystallographic structural studies on a novel pyridine-nitrogen-bridged dimeric nickel(II) complex of a pentadentate N3S2 ligand

The Schiff base formed by condensation of 2,6-diacetylpyridine with S-benzyldithiocarbazate (H₂SNNNS) behaves as a pentadentate ligand, forming a nickel(II) complex of empirical formula Ni(SNNNS)·H₂O that is high-spin with a room-temperature magnetic moment of 2.93 B.M. Spectroscopic data indicate that the ligand coordinates with the nickel(II) ion via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. The crystal and molecular structure of the nickel(II) complex was determined by X-ray crystallography. The complex crystallizes in the monoclinic system, space group C2/c, with a=15.849(2), b=18.830(2) and c=18.447(2) Å and =90°, β=102.179(6)°, γ=90° and Z=8. The crystal structure analysis shows that the complex is dinuclear, [Ni(SNNNS)]₂·2H₂O, in which the nickel(II) ions are bridged by the two pyridine nitrogen atoms of two fully deprotonated ligands. The NiN₄S₂ coordination geometry about each nickel(II) ion can be described as a distorted octahedron. The Schiff base and its nickel(II) complex were tested against four pathogenic bacteria (Bacillus subtilis, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus and B. subtilis (wild type B29) and pathogenic fungi (Saccharomyces ceciricae, Candida albicans, Candida lypolitica and Aspergillus ochraceous) to assess their antimicrobial properties. Both compounds exhibit mild antibacterial and antifungal activities against these organisms. The anticancer properties of these compounds were also evaluated against Human T-lymphoblastic leukaemia cell lines. The Schiff base exhibits marked cytotoxicity against these cells, but its nickel(II) complex is inactive.     

Synthesis and investigation of novel benzimidazole derivatives as antifungal agents

The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975 μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested.     

Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines

A new series of 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines was synthesized and submitted to antibacterial and antifungal activities. Result of the antimicrobial screening showed the compound 4j being the most effective among the various treatments in antimicrobial screening. Compounds 4c, 4d, 4k, and 4l showed moderate activity against the microorganisms tested.