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Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker disease of Italian cypress (Cupressus sempervirens L.). It was also produced, together with several analogues, by different pathogenic Diplodia species and other fungi and showed a broad array of biological activities suggesting its promising application in agriculture and medicine. The anticancer activity of SphA is very potent and cell specific. Recent studies have revealed its unique mode of action. This minireview reports the structures of SphA and its family of natural analogues, their biosynthetic origins, their fungal sources, and biological activities. The preparation of various SphA derivatives is also described as well as the results of structure-activity relationship (SAR) studies and on their potential practical applications.

Two phytotoxic furan derivatives were isolated, together with the well-known fungal and plant phytotoxin tyrosol, from the culture filtrates of Stilbocrea macrostoma. This fungal pathogen isolated from Quercus brantii trees induced wood necrosis and decline symptoms on the host plant in Iran. The two furan derivatives, isolated for the first time from Stilbocrea macrostoma, were identified by spectroscopic methods (essentially 1 D and 2 D 1H and 13C NMR and ESIMS spectroscopy) as 5-hydroxymethylfuraldehyde and 2,5-dihydroxymethylfuran. The phytotoxic activity of the three metabolites was evaluated by leaf puncture assay on holm oak (Quercus ilex L.) and tomato (Lycopersicon esculentum L.) leaves. All compounds induced necrosis on holm oak leaves while very low toxicity was showed against tomato leaves. The two furan derivatives were more toxic than tyrosol and particularly 5-hydroxymethylfuraldehyde was the most phytotoxic compound.

Spencermartinsia viticola is one of the most widespread Botryosphaeriaceae species isolated from grapevines in South Australia and New South Wales vineyards in Australia. A new phytotoxic dipyridine-butane-1,4-diol and a new diacrylic acid derivatives, here named spencertoxin (1) and spencer acid (2), were isolated from the culture filtrates of S. viticola isolate DAR78870 together with p-hydroxybenzaldehyde (3) and 2-(4-hydroxyphenyl) acetic acid (4). Spencertoxin and spencer acid were characterized as 2,3-di(pyridin-3-yl)butane-1,4-diol and (2Z,2′Z)-3,3′-(carbonylbis(oxy))diacrylic acid, respectively, by spectroscopic methods (essentially NMR and HRESIMS). Spencertoxin (1), p-hydroxybenzaldehyde (3) and 2-(4-hydroxyphenyl) acetic acid (4) showed phytotoxicity when the pure compounds were assayed on grapevine leaves of Vitis lambrusca and Vitis vinifera cv. Shiraz. Keywords: Grapevine, Botryosphaeria dieback, Spencermartinsia viticola, Phytotoxins, Spencertoxin and spencer acid

Three previously undescribed metabolites named argyrotoxins A-C, were isolated, together with the well known porritoxinol, its closely related phthalide, a phthalide derivative, zinniol, alternariol and its 4-methyl ether from Alternaria argyroxiphii E.G. Simmons & Aragaki, the causal agent of leaf spot on African mahogany trees, Khaya senegalensis A. Juss. (Meliaceae). The known compounds were identified comparing their physical and spectroscopic properties to those previously reported in literature. Argyrotoxins A-C were characterized essentially by NMR (1H, 13C, COSY, HSQC, HMBC and NOESY NMR spectra) and HRESIMS spectra as 4-(7-methoxy-6-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yloxy)-2-methyl-butyric acid, 5-but-2-enyloxy-N-(2-hydroxyethyl)-2-hydroxymethyl-3-methoxy-4-methyl-benzamide and 1-(5-(hydroxymethyl)-3-methoxy-4-(methoxymethyl)-2-methylphenoxy)-3-methylbutane-2,3-diol, respectively. The absolute configuration of argyrotoxin A was determined through electronic circular dichroism, by applying the biphenyl chiroptical probe approach. The phytoxicity of all metabolites isolated was evaluated by leaf puncture assay at concentration of 1 mg/mL. Zinniol proved to be the most active compound causing necrotic lesions on young leaves of Hedera elix L., Phaseolus vulgaris L. and Quercus ilex L. Argirotoxins A and B were found active, to a minor extent, on Phaseolus vulgaris L. leaves, while porritoxinol exhibited activity on holm oak leaves. The other secondary metabolites herein reported for A. argyroxiphii were inactive.

Biscogniauxia rosacearum, recognized for the first time as a pathogen involved in grapevine trunk diseases in Paveh (west of Iran) vineyards, produced meso-2,3-butanediol (1) as the only phytotoxin. Nectriapyrone (2), (3R)-5-methylmellein (3), (3R)-5-methyl-6-methoxymellein (4), and tyrosol (5) were instead produced as phytotoxins from a strain of the same fungus isolated from oak trees in Zagros forests of Gilan-e Gharb, Kermanshah Province. They were identified comparing their 1H and 13C NMR, ESIMS, and specific optical rotation data with those already reported in the literature. The phytotoxicity of metabolites (1–5) was estimated by leaf puncture assay on Quercus ilex L. and Hedera helix L., and by leaf absorption assay on grapevine (Vitis vinifera L.) at a concentration of 5 × 10−3 and 10−3 M. Tested on grapevine, meso-2,3-butanediol (1) and (3R)-5-methyl-6-methoxymellein (4) resulted to be the most phytotoxic compounds. On Q. ilex, nectriapyrone (2) and tyrosol (5) showed severe necrosis at the highest concentration while none of the compounds (1–5) was active on H. helix. Furthermore, the phytotoxicity of compounds 3 and 4 was also compared with that of some related natural melleins to perform a structure-activity relationship (SAR) study. The results of this study were also discussed.

Grapevine trunk diseases (GTDs) are considered a serious problem to viticulture worldwide. Several GTD fungal pathogens produce phytotoxic metabolites (PMs) that were hypothesized to migrate to the foliage where they cause distinct symptoms. The role of PMs in the expression of Botryosphaeria dieback (BD) symptoms in naturally infected and artificially inoculated wood using molecular and analytical chemistry techniques was investigated. Wood samples from field vines naturally infected with BD and one-year-old vines inoculated with Diplodia seriata, Spencermartinsia viticola and Dothiorella vidmadera were analysed by cultural isolations, quantitative PCR (qPCR) and targeted LC-MS/MS to detect three PMs: (R)-mellein, protocatechuic acid and spencertoxin. (R)-mellein was detected in symptomatic naturally infected wood and vines artificially inoculated with D. seriata but was absent in all non-symptomatic wood. The amount of (R)-mellein detected was correlated with the amount of pathogen DNA detected by qPCR. Protocatechuic acid and spencertoxin were absent in all inoculated wood samples. (R)-mellein may be produced by the pathogen during infection to break down the wood, however it was not translocated into other parts of the vine. The foliar symptoms previously reported in vineyards may be due to a combination of PMs produced and climatic and physiological factors that require further investigation.

An O-specific polysaccharide (OPS) was isolated from the lipopolysaccharide (LPS) of Pseudomonas donghuensis SVBP6, a bacterium with a broad-spectrum antifungal activity in vitro, particularly that against Macrophomina phaseolina. This latter is one of the most virulent and dangerous pathogens of plants, including soybean which is an economically important crop in Argentina today. The OPS was studied by sugar analysis and spectroscopy (1D and 2D 1H and 13C NMR) showing the following trisaccharide repeating unit: →6)-ɑ-D-ManpNAc-(1 → 3)-β- l -Rhap-(1 → 4)-β-D-Glcp-(1→. The crude LPS, the purified LPS and the O-chain were assayed for their antifungal activity against M. phaseolina at 25, 50, 100, and 200 μg plug−1. The results showed that the crude LPS best inhibition was at 200 μg plug−1, able to inhibit the fungus growth by about 45%, while purified LPS and the corresponding OPS, in the same condition, reduced fungus growth by 65%, and 75%, respectively. Furthermore, the purified LPS and OPS significantly reduced the growth of M. phaseolina already at 100 μg plug−1 compared to the crude LPS. The structure of the O-chain is unique among the bacterial LPS and this is the first time that both the antifungal activity of a bacterial LPS and its corresponding O-chain were described.

Dengue fever, caused by dengue virus (DENV), is the most prevalent arthropod-borne viral disease and is endemic in many tropical and subtropical parts of the world, with an increasing incidence in temperate regions. The closely related flavivirus Zika virus (ZIKV) can be transmitted vertically in utero and causes congenital Zika syndrome and other birth defects. In adults, ZIKV is associated with Guillain-Barré syndrome. There are no approved antiviral therapies against either virus. Effective antiviral compounds are urgently needed. Amaryllidaceae alkaloids (AAs) are a specific class of nitrogen-containing compounds produced by plants of the Amaryllidaceae family with numerous biological activities. Recently, the AA lycorine was shown to present strong antiflaviviral properties. Previously, we demonstrated that Crinum jagus contained lycorine and several alkaloids of the cherylline, crinine, and galanthamine types with unknown antiviral potential. In this study, we explored their biological activities. We show that C. jagus crude alkaloid extract inhibited DENV infection. Among the purified AAs, cherylline efficiently inhibited both DENV (50% effective concentration [EC50], 8.8 μM) and ZIKV replication (EC50, 20.3 μM) but had no effect on HIV-1 infection. Time-of-drug-addition and -removal experiments identified a postentry step as the one targeted by cherylline. Consistently, using subgenomic replicons and replication-defective genomes, we demonstrate that cherylline specifically hinders the viral RNA synthesis step but not viral translation. In conclusion, AAs are an underestimated source of antiflavivirus compounds, including the effective inhibitor cherylline, which could be optimized for new therapeutic approaches.

Ophiobolin A is a secondary phytotoxic metabolite produced by some pathogenic fungal species responsible for severe plant diseases, considered to play a role in disease development and symptom appearance. Herein we investigated whether the phytotoxic activities of ophiobolin A against weed species could be improved by nanoencapsulation. Given the rapid natural degradation of the compound, it was hoped that nanoencapsulation would prolong the phytotoxic effects or enhance the bioactivity, thus leading to improved weed control capabilities. This article presents an assessment of the effectiveness of encapsulated ophiobolin A on 11 commonly found weed species, compared to the pure ophiobolin, to the particle alone, and a combination of mixed particles and ophiobolin A, by applying the solution droplets to both intact or injured leaf surface, on the adaxial or abaxial side. The bioassays showed the improved efficacy of the encapsulated ophiobolin, and the need for leaf lesions to diffuse the particles into the tissues.[Formula: see text].

In an attempt to search for selective inhibitors against the SARS-CoV-2 which caused devastating of lives and livelihoods across the globe, 415 natural metabolites isolated from several plants, fungi and bacteria, belonging to different classes, were investigated. The drug metabolism and safety profiles were computed in silico and the results showed seven compounds namely fusaric acid, jasmonic acid, jasmonic acid methyl ester, putaminoxin, putaminoxin B and D, and stagonolide K were predicted to having considerable absorption, metabolism, distribution and excretion parameters (ADME) and safety indices. Molecular docking against the receptor binding domain (RBD) of spike glycoprotein (S1) and the main protease (Mpro) exposed the compounds having better binding affinity to main protease as compared to the S1 receptor binding domain. The docking results were compared to an antiviral drug penciclovir reportedly of clinical significance in treating the SARS-CoV-2 infected patients. The results demonstrated the test compounds jasmonic acid, putaminoxins B and D bound to the HIS-CYS catalytic dyad as well as to other residues within the MPro active site with much greater affinity than penciclovir. The findings of the study suggest that these compounds could be explored as potential SARS-CoV-2 inhibitors, and could further be combined with the experimental investigations to develop effective therapeutics to deal with the present pandemic.

This review, covering the literature from 1966 to the present (2020), describes naturally occurring fungal bioactive anthraquinones and analogues biosynthesized by the acetate route and concerning several different functionalized carbon skeletons. Hydrocarbons, lipids, sterols, esters, fatty acids, derivatives of amino acids, and aromatic compounds are metabolites belonging to other different classes of natural compounds and are generated by the same biosynthetic route. All of them are produced by plant, microorganisms, and marine organisms. The biological activities of anthraquinones and analogues comprise phytotoxic, antibacterial, antiviral, anticancer, antitumor, algicide, antifungal, enzyme inhibiting, immunostimulant, antiplatelet aggregation, cytotoxic, and antiplasmodium activities. The review also covers some practical industrial applications of anthraquinones.

In this study, chitosan (C) tripolyphosphate (T) sub-micro particles containing ungeremine (CTUn), an alkaloid particularly active against Penicillium roqueforti, a fungus responsible of the bakery products deterioration, were prepared through external gelation crosslinking process. The particles were included in a thermoplastic starch based polymer Mater-Bi (MBi), and MBi/CTUn bioactive biocomposites were obtained. The films showed bioactivity against P. roqueforti. In particular, the bioassays were performed on films with different concentration of CTUn and at different pH values. CTUn particles influenced MBi crystallization (DSC analysis) and promoted thermal degradation of MBi starch component (TGA). Morphological analysis confirmed even distribution of sub-micro particles into the polymeric matrix. Water permeability slightly increased, as expected, whereas oxygen permeability decreased. Tensile tests showed CTUN sub-microparticles improved rigidity and tensile strength of the films at the expense of ductility. Finally, MBi/CTUn biocomposites evidenced interesting performances potentially exploitable in bioactive bakery based food packaging materials.

Background The organic extracts (OEs) of Dittrichia viscosa, a ruderal plant common in the Mediterranean regions, proved to have herbicidal properties. In order to improve OE effectiveness and to develop novel eco-friendly bioherbicidal products, different amounts of OE were included in poly(butylene succinate)- and polycaprolactone-based films (PBS and PCL, respectively). Particular attention was given to the study of interactions between the polymers and OEs, with a deep spotlight concerning the influence of OEs on structural, morphological and thermal properties of both polymers, in order to assess the OE releasing kinetics from the matrices and its tuned herbicidal action against seeds. Results The bioassays carried out on Lepidium sativum and Phelipanche ramosa seeds evidenced a more controlled and effective OE release by PBS than PCL, and a longer lasting efficacy by the polymers with a higher OE content. The chemical-physical analyses were performed on films before and after biological assays. The thermogravimetric analysis confirmed that OE was a thermal stabilizer of the polymer; the presence of OE and polymer separated degradative kinetics suggested that only a partial and functional miscibility between polymers and OE occurred. The morphological analysis confirmed the good OE dispersion between PBS and PCL molecular chains. Infrared spectroscopy highlighted the enhanced hydrolysed structure of the doped polymers after the bioassays. These outcomes well matched the quantitative information outlined by release kinetics. Discussion The use of biodegradable polymers allows the effectiveness and tuning of the release of the formulated bioactive compounds to be improved. The easy-to-obtain and easy-to-formulate OE could become a suitable and environmentally friendly instrument in weed management programmes.

In this study, chitosan based microbeads containing Ungeremine, an antimicrobial alkaloid particularly active against Penicillium roqueforti, a filamentous fungus responsible of the bakery products deterioration, were prepared by external gelation by using sodium tripolyphosphate (TPP) as crosslinking agent. The stability of the beads, as well as the loading efficiency of the bioactive molecule, were assessed at different pH and TPP concentrations resulting particularly enhanced at low pH. All the microbeads evidenced antimicrobial activity against Penicillium roqueforti. The release kinetics of Ungeremine was tailored by opportunely modulating pH and TPP concentrations. Morphological analysis evidenced the improvement of the structural crosslinking density of microbeads including Ungeremine and spectroscopic analysis emphasized the active participation of Ungeremine to the crosslinking process occurring between chitosan and TPP. Finally, thermogravimetric analysis confirmed the increasing of free volume in three-dimensional networks and their liability to thermal degradation.

The fungal jasmonate lasiojasmonate A functions as a source of jasmonic acid that activates the JA-isoleucine pathway in Arabidopsis., Jasmonates are signaling compounds that regulate plant responses to stress. Jasmonic acid (JA) is the direct precursor of the bioactive plant hormone JA-isoleucine (JA-Ile), the ligand of the CORONATINE INSENSITIVE 1–jasmonate ZIM-domain (COI1–JAZ) co-receptor complex. JA, its methyl ester, and three furanonyl esters were recently isolated from the grapevine pathogen Lasiodiplodia mediterranea. The JA ester lasiojasmonate A (LasA) is the first reported naturally occurring JA-furanone, and its mode of action has not yet been elucidated. Here, we show that LasA activates many JA-regulated responses in planta, including protein degradation, gene expression, and physiological processes. These in vivo effects require LasA conversion into JA, formation of JA-Ile, and its recognition by the plant JA-Ile perception complex. These findings suggest a mode of action of the natural fungal LasA as an inactive JA pool that can be transformed into the bioactive JA-Ile form. We propose that fungal production of JA derivates such as LasA occurs at late infection stages to induce plant JA responses such as cell death, and can facilitate fungal infection.

This manuscript describes antifungal, structural, thermal and morphological properties of a novel, eco-friendly bioplastic film, based on poly(butylenesuccinate) and cavoxin, a chalcone phytopathogenic metabolite, isolated from cultures by the fungus Phoma cava and included inside the biodegradable polymeric matrix. The antagonistic activity of the film explored against two fungal food contaminants Penicilliumroqueforti and Aspergillusniger, highlighted that cavoxin was fungicide at MIC concentrations. The chemico-physical analysis were performed on films before and after antifungal activity. Thermal analysis evidenced both the higher thermal stability of poly(butylenesuccinate) and cavoxin blend and the sharp nucleating action of cavoxin on the polymer. Infrared spectroscopy highlighted the presence of physical interaction between the polar groups of the blend components, whereas gel permeation chromatography highlighted that the hydrolytic effect of cavoxin on poly(butylenesuccinate) was responsible for the diffusion and releasing of the biomolecule from the matrix and UV–Vis spectroscopy provided quantitative information of release kinetics. Finally, morphological analysis confirmed both the polymeric surface hydrolysis exerted by cavoxin, and the adhesion of fungal spores on films after contact occurred during the antifungal assay.

An O-specific polysaccharide (OPS) was isolated from the lipopolysaccharide of Pseudomonas mediterranea strain C5P1rad1, the causal agents of tomato pith necrosis and Chrysanthemum stem rot, and studied by one- and two-dimensional 1 H and 13 C NMR spectroscopy. The following structure of the trisaccharide repeating unit of the OPS was established, which, to our knowledge, is unique among the known bacterial polysaccharide structures: →4)-β- d -Man p NAc3NAcA-(1 → 4)-β- d -Man p NAc3NAcA-(1 → 3)-α- d -Qui p NAc4NAc-(1→ where QuiNAc4NAc and ManNAc3NAcA indicate 2,4-diacetamido-2,4,6-trideoxyglucose and 2,3-diacetamido-2,3-dideoxymannuronic acid, respectively. Pre-treatment of leaves with LPS or OPS preparations at 250 and 50 μg mL −1 did not inhibit development of a hypersensitivity reaction induced by P. mediterranea C5P1rad1 on tobacco, tomato and chrysanthemum plants. The same preparations at 250 μg mL −1 partially prevented elicitation of the hypersensitivity reaction by Pseudomonas syringae KVPT7RC on chrysanthemum but not tobacco and tomato.

Plants belonging to the Amaryllidaceae family are well known for their ornamental and medicinal use. Plant members of this group are distributed through both tropical and subtropical regions of the world and are dominant in Andean South America, the Mediterranean basin, and southern Africa. Amaryllidaceae plants have been demonstrated to be a good source of alkaloids with a large spectrum of biological activities, the latter being strictly related to the absolute stereochemistry of the alkaloid scaffold. Among them, great importance for practical applications in medicine has galanthamine, which has already spawned an Alzheimer's prescription drug as a potent and selective inhibitor of the enzyme acetylcholinesterase. Furthermore, lycorine as well as its related isocarbostyryl analogs narciclasine and pancratistatine have shown a strong anticancer activity in vitro against different solid tumors with malignant prognosis. This review addresses the assignment of the absolute configuration of several Amaryllidaceae alkaloids and its relationship with their biological activities.

Phytotoxic metabolites produced in liquid culture by six species of Lasiodiplodia isolated in Brazil and causing Botryosphaeria dieback of grapevine were chemically identified. As ascertained by LC/MS, L. brasiliense, L. crassispora, L. jatrophicola, and L. pseudotheobromae produced jasmonic acid, and L. brasiliense synthesized, besides jasmonic acid, also (3R,4S)-4-hydroxymellein. L. euphorbicola and L. hormozganensis produced some low molecular weight lipophilic toxins. Specifically, L. euphorbicola produced (-)-mellein, (3R,4R)-(-)- and (3R,4S)-(-)-4-hydroxymellein, and tyrosol, and L. hormozganensis synthesized tyrosol and p-hydroxybenzoic acid. This is the first report on the production of the above cited metabolites from L. euphorbicola and L. hormozganensis. The phytotoxic activity of the metabolites produced is also discussed and related to the symptoms these pathogens cause in the grapevine host plants.

The organic extract of the aerial parts of Dittrichia viscosa, a perennial native plant of the Mediterranean basin, showed a significant acaricidal activity against Varroa destructor, the parasite mite of Apis mellifera, commonly called honey bee. Among the metabolites isolated from the organic extract of this Asteraceae, α-costic acid showed to be one of the compounds responsible for the toxic activity exhibited by the crude plant extract on this parasite mite species. In addition to the toxic effect a clear acaricidal response has been recorded when the parasitic mite was exposed to 1 mg/mL concentration of α-costic acid while no effects have been showed on honey bees using the same compound at the same concentration. This finding suggests a potential use of α-costic acid to control Varroa mites. The possibility to reliably achieve absolute configuration of α-costic acid by DFT computational analysis of chiroptical spectra has been also demonstrated.†

Pyrenophoric acid (P-Acid), P-Acid B, and P-Acid C are three phytotoxic sesquiterpenoids produced by the ascomycete seed pathogen Pyrenophora semeniperda, a fungus proposed as a mycoherbicide for biocontrol of cheatgrass, an extremely invasive weed. When tested in cheatgrass bioassays, these metabolites were able to delay seed germination, with P-Acid B being the most active compound. Here, we have investigated the cross-kingdom activity of P-Acid B and its mode of action, and found that it activates the abscisic acid (ABA) signaling pathway in order to inhibit seedling establishment. P-Acid B inhibits seedling establishment in wild-type Arabidopsis thaliana, while several mutants affected in the early perception as well as in downstream ABA signaling components were insensitive to the fungal compound. However, in spite of structural similarities between ABA and P-Acid B, the latter is not able to activate the PYR/PYL family of ABA receptors. Instead, we have found that P-Acid B uses the ABA biosynthesis pathway at the level of alcohol dehydrogenase ABA2 to reduce seedling establishment. We propose that the fungus P. semeniperda manipulates plant ABA biosynthesis as a strategy to reduce seed germination, increasing its ability to cause seed mortality and thereby increase its fitness through higher reproductive success., The fungus Pyrenophora semeniperda produces pyrenophoric acid B, a small molecule that exploits the plant ABA biosynthetic pathway to reduce seed germination, increasing its reproductive success.

Aphids are noxious insect pests of major crops including cereals and legumes. Particularly, pea aphid (Acyrthosiphon pisum) causes significant yield and quality loses in pea. Crop protection is largely based on noxious chemical pesticides which have prompted a renewed interest in the discovery of natural products as alternatives to synthetic insecticides. In this study different classes of natural compounds were tested in dual choice bioassays to evaluate their feeding deterrence and mortality effect on pea aphid. High feeding deterrence was produced by some of the compounds, particularly1-hexadecanol, gliotoxin, cyclopaldic acid and seiridin. On the contrary, aphid mortality was low although significant for 1-heptadecanol, cytochalasin A, 1-nonadecanol and gliotoxin. Phytotoxicity assessment showed low or imperceptible plant damaged for cytochalasin A, seiridin and 1-nonadecanol. The results obtained showed the potential of seiridin to be used as an alternative to synthetic insecticides., This work was supported by the Spanish Ministry of Economy and Competitiveness FPI program and projects [grant number AGL2014-52871-R], [grant number AGL2017-82907-R]; the FEDER; the EU-FP7-LEGATO [grant number 613551].

Ophiobolin A is a fungal secondary metabolite that was found to have significant activity against apoptosis-resistant glioblastoma cells through the induction of a non-apoptotic cell death, offering an innovative strategy to combat this aggressive cancer. The current article aims to make the bridge between the anti-cancer effects of ophiobolin A and its unique reaction with primary amines and suggests that pyrrolylation of lysine residues on its intracellular target protein(s) and/or phosphatidylethanolamine lipid is responsible for its biological effects. The article also discusses chemical derivatization of ophiobolin A to establish first synthetically generated structure-activity relationship. Finally, the reported total synthesis efforts toward the ophiobolin class of sesterterpenes are discussed and identified as a fertile area for improvement in pursuit of these molecules as anticancer agents., SCOPUS: re.j, info:eu-repo/semantics/published

Many types of cancer, including glioma, melanoma, non-small cell lung cancer (NSCLC), among others, are resistant to proapoptotic stimuli and thus poorly responsive to current therapies based on the induction of apoptosis in cancer cells. The current investigation describes the synthesis and anticancer evaluation of unique C12-Wittig derivatives of polygodial, a sesquiterpenoid dialdehyde isolated from Persicaria hydropiper (L.) Delabre. These compounds were found to undergo an unprecedented pyrrole formation with primary amines in a chemical model system, a reaction that could be relevant in the biological environment and lead to the pyrrolation of lysine residues in the target proteins. The anticancer evaluation of these compounds revealed their promising activity against cancer cells displaying various forms of drug resistance, including resistance to proapoptotic agents. Mechanistic studies indicated that compared to the parent polygodial, which displays fixative general cytotoxic action against human cells, the C12-Wittig derivatives exerted their antiproliferative action mainly through cytostatic effects explaining their activity against apoptosis-resistant cancer cells. The possibility for an intriguing covalent modification of proteins through a novel pyrrole formation reaction, as well as useful activities against drug resistant cancer cells, make the described polygodial-derived chemical scaffold an interesting new chemotype warranting thorough investigation., SCOPUS: ar.j, info:eu-repo/semantics/published

An undescribed substituted dihydroxanthene-1,9-dione, named funiculosone, was isolated together with its two analogues identified as mangrovamide J and ravenelin, from the culture filtrates of Talaromyces funiculosus (Thom) Samson, Yilmaz, Frisvad & Seifert (Trichocomaceae), an endolichenic fungus isolated from lichen thallus of Diorygma hieroglyphicum (Pers.) Staiger & Kalb (Graphidaceae), in India. Funiculosone was characterized, essentially by spectroscopic methods, as 4,8,9a-trihydroxy-3,4a-dimethyl-4a,9a-dihydro-4H-xanthene-1,9-dione. Its relative stereochemistry was deduced by single crystal X-ray analysis while the absolute configuration was assigned as 4S,4aS,9aS by ECD spectra in comparison to that of the closely related mangrovamide J. This latter, to which, not being an amide, an inappropriate common name was given, was only recently isolated, together with undescribed and known prenylatedindole alkaloids and chromone derivatives from an unidentified Penicillium sp. X-ray structural analysis of the isolated mangrovamide J, for which no biological activity was previously reported, revealed polymorphism and a new crystalline phase is described. All the compounds displayed antibacterial activity with an IC50 range 23–104 μg/mL when assayed against Escherichia coli Escherich and Staphylococcus aureus Ogston. Funiculosone also showed anticandidal activity against Candida albicans Berkhout with an IC50 35 μg/mL.

(+)-epi-Epoformin (1), is a fungal cyclohexene epoxide isolated together with diplopimarane and sphaeropsidins A and C, a nor-ent-pimarane and two pimaranes, from the culture filtrates of Diplodia quercivora, a fungal pathogen for cork oak in Sardinia, Italy. Compound 1 possesses a plethora of biological activities including: antifungal, zootoxic and phytotoxic activity. The last activity and the peculiar structural feature of 1 suggested to carry out a structure activity relationship study, preparing eight key hemisynthetic derivatives and their phytotoxicity was assayed. The complete spectroscopic characterization and the activity in the etiolated wheat coleoptile bioassay of all the compounds is reported. Most of the compounds inhibited growth and some of them had comparable or higher activity than the natural product and the reference herbicide Logran. As regards the structure-activity relationship, the carbonyl proved to be essential for their activity of 1, as well as the conjugated double bond, while the epoxide could be altered with no significant loss.

Electronic circular dichroism (ECD) and discrete wavelength resolved specific optical rotations, referred to as optical rotatory dispersion (ORD), have been remeasured for inuloxin C and analysed with corresponding quantum chemical (QC) predicted data for all diastereomers of inuloxin C. The QC‐predicted sign of ORD and of a major ECD band are found to match the experimental observations for more than one diastereomer. However, these ECD and ORD analyses combined with electronic dissymmetry factor analyses narrowed the choices of absolute configuration (AC) of inuloxin C to (5R,7S,8R,10R) and (5S,7S,8S,10S). Supplementing these analyses with corresponding analyses for acetylated inuloxin C resulted in a unique choice for the AC of inuloxin C as (5S,7S,8S,10S). This result is independent of NMR analysis. Furthermore, this AC is in full agreement with previously determined relative configuration by NMR and the AC derived therefrom using ECD and ORD. Therefore, the present study identifies a pathway for determining the ACs of chiral molecules with multiple stereogenic centers when relative configurations are not known, or when it is desired to deduce ACs independent of the known relative configurations.

Polyphenols were characterized from Dothiorella vidmadera (DAR78993), which was isolated from a grapevine in Australia. In total, six polyphenols were isolated including a new polyphenol characterized by a spectroscopic method (essentially NMR and HR ESIMS) as 5-hydroxymethyl-2-isopropoxyphenol. Tyrosol, benzene-1,2,4-triol, resorcinol, 3-(hydroxymethyl)phenol, and protocatechuic alcohol, the latter being the main metabolite, were also isolated. Although these are already known as naturally occurring compounds in microorganisms and plants, this is the first time they have been isolated from fungal organisms involved in grapevine trunk disease. When assayed on tomato seedlings, all the compounds show similar phytotoxic effects. However, when assayed on grapevine leaves (Vitis vinifera cv Shiraz), resorcinol was the most toxic compound, followed by protocatechuic alcohol and 5-hydroxymethyl-2-isopropoxyphenol.

Ambrosia artemisiifolia L. is responsible for serious allergies induced on humans. Different approaches for its control were proposed during the COST Action FA1203 “Sustainable management of Ambrosia artemisiifolia in Europe” (SMARTER). Fungal secondary metabolites often show potential herbicidal activity. Three phytotoxins were purified from the fungal culture filtrates of Colletotrichum gloeosporioides, isolated from infected leaves of A. artemisiifolia. They were identified by spectroscopic and chemical methods as colletochlorin A, orcinol and tyrosol (1, 2 and 3). The absolute configuration 6’R to colletochlorin A was assigned for the first time applying the advanced Mosher’s method. When assayed by leaf-puncture on A. artemisiifolia only 1 caused the appearance of large necrosis. The same symptoms were also induced by 1 on ambrosia plantlets associated with plant wilting. On Lemna minor, colletochlorin A caused a clear fronds browning, with a total reduction in chlorophyll content.

From the culture filtrates of Diaporthella cryptica, an emerging hazelnut pathogen, 2-hydroxy-3-phenylpropanoate methyl ester and its 3-(4-hydroxyphenyl) and 3-(1H-indol-3-yl) analogues, named crypticins A-C, were isolated together with the well-known tyrosol. Crypticins A-C were identified by spectroscopic (essentially nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry) methods. The R absolute configuration (AC) of crypticin A was determined by comparing its optical rotation and electronic circular dichroism (ECD) spectrum with those of papuline, the methyl ester of (-)(S)-phenyllactic acid isolated as the main phytotoxin of Pseudomonas syringae pv. papulans, responsible for apple blister spot. The ACs of crypticins B and C were determined by time-dependent density functional theory calculations of their ECD spectra. Papuline and the new metabolites herein isolated, except tyrosol, were tested at 1 mg/mL on cork oak, grapevine, hazelnut, and holm oak leaves using the leaf puncture assay. They were also tested on tomato cuttings at 0.5 and 0.05 mg/mL. In the leaf puncture assay, none of the compounds was found to be active. Crypticin C and papuline were active in the tomato cutting assay. Additionally, crypticin C displayed moderate inhibitory effect against Phytophthora cambivora. © 2018 American Chemical Society.

A strain of Fusarium oxysporum was isolated from grapevine showing heavy decline disease in a vineyard of Veneto region in Italy. The fungus showed to produce phytotoxic metabolites when grown in liquid culture. The main metabolite was identified as fusaric acid produced for the first time as a phytotoxin by a strain of F. oxysporom isolated from diseased grapevine plants. Its quantification in the fungus cultures filtrates was accomplished by HPLC. When tested on tobacco by leaf-puncture assay fusaric acid at 0.5 mg/mL induced the formation of extensive necrosis.

A new alkaloid, belonging to the pretazettine group of Amaryllidaceae alkaloids, was isolated from dried bulbs of Narcissus jonquilla quail and named jonquailine. Its structure, including the absolute configuration, was elucidated using various NMR, ECD and ESI MS techniques. Initial biological evaluation revealed significant antiproliferative effects against glioblastoma, melanoma, uterine sarcoma and non-small-cell lung cancer cells displaying various forms of drug resistance, including resistance to apoptosis and multi-drug resistance. Jonquailine was also found to synergize with paclitaxel in its antiproliferative action against drug-resistant lung cancer cells. The results obtained compared with literature data also showed that the hydroxylation at C-8 is an important feature for the anticancer activity but this seems unaffected by the stereochemistry or the acetalization of the lactol.

Two processing tomato hybrids and five N fertilization rates were evaluated regarding their biomass, fruit yield, and saccharification potential. Although no difference was detected between the hybrids, both for fruit and residual biomass yield, 106 kg ha −1 N fertilization rate showed the highest fruit mass and 186 kg ha −1 resulted in the highest residual biomass production. The biomass in the hybrid Kero had higher content of total and crystalline cellulose compared to Defender. N fertilization significantly changed biomass composition. Eighty kg ha −1 N led to the highest lignin, hemicellulose and pectin content, whereas the 159 kg ha −1 applications caused the highest percentage of total and crystalline cellulose. Xylose was the most abundant monosaccharide in hemicelluloses, whereas fucose was the lest abundant. The hybrid Kero gave higher ethanol potential production than Defender and both hybrids reached the highest values under 159 kg ha −1 of N. Alkali pre-treatment caused the highest values of saccharification and hot water the lowest. The hybrid Kero showed higher saccharification potential than Defender and 159 kg ha −1 N fertilization rate led to the best results. We show that tomato residual biomass is an interesting lignocellulosic feedstock for ethanol production and both hybrid and nitrogen fertilization rate significantly affects the biomass chemical composition and saccharification potential of the residual biomass.

Orobanche and Phelipanche species (the broomrapes) are root parasitic plants, some of which cause heavy yield losses on important crops. The development of herbicides based on natural metabolites from microbial and plant origin, targeting early stages on parasitic plant development, might contribute to the reduction of broomrape seed bank in agricultural soils. Therefore, the effect of metabolites belonging to different classes of natural compounds on broomrape seed germination and radicle development was assayed in vitro. Among the metabolites tested, epi-sphaeropsidone, cyclopaldic acid, and those belonging to the sesquiterpene class induced broomrape germination in a species-specific manner. epi-Epoformin, sphaeropsidin A, and cytochalasans inhibited germination of GR24-treated broomrape seeds. The growth of broomrape radicle was strongly inhibited by sphaeropsidin A and compounds belonging to cyclohexene epoxide and cytochalasan classes. Broomrape radicles treated with epi-sphaeropsidone developed a layer of papillae while radicles treated with cytochalasans or with sphaeropsidin A turned necrotic. These findings allow new lead natural herbicides for the management of parasitic weeds to be identified., The research was carried out in part in the frame of Programme STAR, financially supported by UniNA and Compagnia di San Paolo, and in part in the frame of project FP7-ARIMNetMEDILEG. This work was carried out within the COST ACTION FA1206 Strigolactones: biological roles and applications. Monica Fernandez-Aparicio has received support from the ́ European Union, in the framework of the Marie-Curie FP7 COFUND People Programme, through the award of an AgreenSkills’ fellowship (under grant agreement n° PCOFUNDGA-2010−267196). A. E. is associated with the Istituto di Chimica Biomolecolare del CNR, Pozzuoli, Italy.

Recent analyses on fungal jasmonic acid (JA)-containing metabolites suggest a mode-of-action of these naturally occurring compounds as inactive storage pools of JA. Plants and/or fungi can catabolize JA into the bioactive jasmonyl-isoleucine (JA-Ile) that in turn activates the JA-Ile-pathway in planta. To extend our knowledge on JA-derivates related to natural occurring JA conjugates, N-[(-)-jasmonyl]-S-tyrosin (JA-Tyr) and the ester JA-Sei between JA and seiridin, a fungal disubstituted furanone, were synthesized. The classical procedures for ester synthesis were applied for compound JA-Sei, while N-[(-)-jasmonyl]-S-tyrosin was synthesized with an optimized procedure. JA-Tyr and JA-Sei were characterized by spectroscopic method (essentially 1D and 2D NMR spectroscopy and ESI-MS) and their stereochemical composition was determined by means of HPLC and circular dichroism analysis. Finally, the activity of these JA-derivates was analyzed in planta. JA-Tyr and JA-Sei trigger JA-regulated plant responses, such as protein degradation and growth inhibition. These effects require the conversion of JA into JA-Ile and its recognition by the plant JA-Ile perception complex COI1-JAZ. Overall, these data suggest a mode-of-action of JA-Tyr and JA-Sei as inactive pool of JA that can be transformed into the bioactive JA-Ile to induce the canonical JA-Ile-pathway.

The winter annual grass Bromus tectorum (cheatgrass) has become highly invasive in semiarid ecosystems of western North America. In these areas, a natural phenomenon, complete cheatgrass stand failure (‘die-off’), is apparently caused by a complex interaction among soilborne fungal pathogens. Several Fusarium strains belonging to the Fusarium tricinctum species complex were isolated from these soils and found to be pathogenic on B. tectorum seeds. One of these strains was produced in cheatgrass seed culture to evaluate its ability to produce phytotoxins. Six metabolites were isolated and identified by spectroscopic methods (essentially 1D and 2D NMR and ESIMS) as acuminatopyrone (1), blumenol A (2), chlamydosporol (3), isochlamydosporol (4), ergosterol (5) and 4-hydroxybenzaldehyde (6). Upon testing against B. tectorum in a seedling bioassay, (6) the coleoptile and radicle length of cheatgrass seedlings were significantly reduced. Compounds 1 and 2 showed moderate activity, while 3–5 were not significantly different from the control.

A new tetrasubstituted pyran-2-one and a new dihydrobenzofuran, named colletochlorins E and F (1 and 2, respectively), were isolated from the culture filtrates of the fungus Colletotrichum higginsianum together with the already known colletochlorin A, 4-chloroorcinol, and colletopyrone. Colletochlorin E, the main metabolite, and colletochlorin F were characterized by spectroscopic (NMR, HRESIMS) and chemical methods as 3-[7-chloro-4-hydroxy-2-(1-hydroxy-1-methylethyl)-6-methyl-2,3-dihydrobenzofuran-5-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 7-chloro-2-(1-hydroxy-1-methylethyl)-6-methyl-2,3-dihydrobenzofuran-4-ol, respectively. The absolute configuration 2′S of 1 was deduced by X-ray diffractometric analysis, whereas 2S of 2 was deduced by comparison of its NMR and CD data with those of 1. When assayed by leaf puncture on Sonchus arvensis and tomato leaves, 2 caused quite large necrosis (>1 cm), whereas 4-chloroorcinol proved to be the most active compound. These results were confirmed by those obtained in assays on Lemna minor and Phelipanche ramosa seed germination. Furthermore 1, colletochlorin A and colletopyrone were less or modestly active in the latter assay, respectively. Interestingly, the phytotoxicity was not associated with an antibiotic activity, whereas only 4-chloroorcinol and colletochlorin F exhibited zootoxic activity.

The fungal pathogen Cochliobolus australiensis isolated from infected leaves of the invasive weed buffelgrass (Pennisetum ciliare) was grown in vitro to evaluate its ability to produce phytotoxic metabolites that could potentially be used as natural herbicides against this weed. Two new tetrasubstituted 3-chromanonacrylic acids, named chloromonilinic acids C (1) and D (2), were isolated from the liquid cultures of C. australiensis, together with the known chloromonilinic acid B. Chloromonilinic acids C and D were characterized by spectroscopic and chemical methods as (E)-3-chloro-3-[(5-hydroxy-3-(1-hydroxy-2-methoxy-2-oxoethyl)-7-methyl-4-oxo-4H-chromen-2-yl)]acrylic acid and (Z)-3-chloro-3-[(5-hydroxy-3-(2-methoxy-2-oxoethyl)-7-methyl-4-oxo-4H-chromen-2-yl)]acrylic acid, respectively. The stereochemistry of chloromonilinic acids C and D was determined using a combination of spectroscopic and computational methods, including electronic circular dichroism. The fungus produced these compounds in two different liquid media together with cochliotoxin, radicinin, radicinol, and their 3-epimers. The radicinin-related compounds were also produced when the fungus was grown in wheat seed solid culture, but chloromonilinic acids were not found in the solid culture organic extract. All three chloromonilinic acids were toxic to buffelgrass in a seedling elongation bioassay, with significantly delayed germination and dramatically reduced radicle growth, especially at a concentration of 5 × 10-3 M.

Cavoxin is a tetrasubstituted phytotoxic chalcone and cavoxone is the corresponding chroman-4-one, both produced in vitro by Phoma cava, a fungus isolated from chestnut. Cavoxin showed biofungicide potential against fungal species responsible for food moulding. Therefore, cavoxin has potential to be incorporated into biopolymer to generate ‘intelligent food packaging’. To reach this objective, large-scale production of cavoxin by P. cava fermentation needs to be optimized. A rapid and efficient method for cavoxin analysis, as well as of cavoxone, in the fungal culture filtrates and the corresponding organic extracts is the first experimental step. Thus, a HPLC method was developed and applied to quantify cavoxin and cavoxone production in two different fungal culture conditions. The analysis proved that cavoxin production in stirred culture filtrates is significantly higher than in static ones.

Ophiobolin A (O-A) is a sesterpenoid with numerous biological activities, including potential anticancer effects. Its production at an industrial level is hampered due to inability of fungus Bipolaris maydis to biosynthesise it in vitro in large amount. Among the environmental factors regulating fungal metabolism, light plays a crucial role. In this study, the use of different light wavelength (light emitting diodes (LEDs)) was evaluated to increase the O-A production. The white light allowed the highest production of the metabolite. The blue and green lights showed an inhibitory effect, reducing the production to 50%, as well as red and yellow but at a lower level. No correlation between fungal growth and metabolite production was found in relation to the light type. A novel application of LED technologies, which can be optimised to foster specific pathways and promote the production of metabolites having scientific and industrial interest was proposed.

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin- 1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo [d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time. Compounds 1–6 were evaluated against the Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal activity with an LD50 = 2.29 ± 0.049 μg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity.

Orobanche crenata is a parasitic weed that causes severe yield losses in important grain and forage legume crops. Cereals have been reported to inhibit O. crenata parasitism when grown intercropped with susceptible legumes, but the responsible metabolites have not been identified. A number of metabolites have been reported in cereals that have allelopathic properties against weeds, pests, and pathogens. We tested the effect of several allelochemicals identified in cereals on O. crenata seed germination and radicle development. We found that 2-benzoxazolinone, its derivative 6-chloroacetyl-2-benzoxazolinone, and scopoletin significantly inhibited O. crenata seed germination. Benzoxazolinones, l-tryptophan, and coumalic acid caused the stronger inhibition of radicle growth. Also, other metabolites reduced radicle length, this inhibition being dose-dependent. Only scopoletin caused cell necrotic-like darkening in the young radicles. Prospects for their application to parasitic weed management are discussed. © 2013 American Chemical Society., This research is supported by projects FP7-ARIMNet-MEDILEG and AGL2011-22524 (cofinanced by FEDER funds).

A novel pyrroloindole terpenoid, named fischerindoline (1), was isolated together with the known metabolites eurochevalierine, pyripyropenes A and E, sequiterpene, gliotoxin, and bis(dethio)bis(methylthio)gliotoxin from solid and liquid cultures of Neosartorya pseudofischeri. Fischerindoline was characterized as 3a-hydroxy-8-methyl-1,2,3,3a,8,8a-hexahydro-pyrrolo[2,3-b]indole-2-carboxylic acid, 2-acetoxy-8a-hydroxy-5-isopropenyl-3,8-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl ester by spectroscopic and chemical methods. Fischerindoline displays in vitro growth inhibitory activity in six human and mouse cancer cell lines.

A new phytotoxic unrearranged ent-pimaradiene diterpene, named chenopodolin, was isolated from the liquid culture of Phoma chenopodicola, a fungal pathogen proposed for the biological control of Chenopodium album, a common worldwide weed of arable crops such as sugar beet and maize. The structure of chenopodolin was established by spectroscopic, X-ray, and chemical methods as (1S,2S,3S,4S,5S,9R,10S,12S,13S)-1,12-acetoxy-2,3-hydroxy-6-oxopimara-7(8),15-dien-18-oic acid 2,18-lactone. At a concentration of 2 mg/mL, the toxin caused necrotic lesions on Mercurialis annua, Cirsium arvense, and Setaria viride. Five derivatives were prepared by chemical modification of chenopodolin functionalities, and some structure–activity relationships are discussed.

The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.

Two isolates of Neofusicoccum australe belonging to ITS haplotypes H4 and H1 and associated with grapevine cordon dieback and branch dieback of Phoenicean juniper, respectively, have been shown to produce in vitro structurally different secondary metabolites. From the strain BOT48 of N. australe (haplotype H4) a new cyclohexenone oxide, namely, cyclobotryoxide, was isolated together with 3-methylcatechol and tyrosol. Cyclobotryoxide was characterized as (1S,5R,6S)-5-hydroxy-3-methoxy-4-methyl-7-oxabicyclo[4.1.0]hept-3-en-2-one by spectroscopic, optical, and chemical methods. The strain BL24 (haplotype H1) produced tyrosol along with botryosphaerone D and (3S,4S)-3,4,8-trihydroxy-6-methoxy-3,4- dihydro-1(2H)-naphthalenone. The metabolites obtained from both strains were tested at four concentrations on leaves of grapevine cv. Cannonau, holm oak, and cork oak by the leaf puncture assay. Cyclobotryoxide proved to be the most phytotoxic compound. Tyrosol and cyclobotryoxide were also tested on detached grapevine leaves at concentrations of 0.25 and 0.5 mg/mL. Only cyclobotryoxide was found to be active in this bioassay.

Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance., SCOPUS: ar.j, info:eu-repo/semantics/published

In this study we report the effects of fungal metabolites isolated from cultures of the fungus Trichoderma citrinoviride ITEM 4484 on the feeding preference of the aphid Rhopalosiphum padi, a major pest of cereal crops. Different phagodeterrent metabolites were purified by a combination of direct and reverse phase column chromatography and thin-layer chromatography. Chemical investigations, by spectroscopic and chemical methods, led to the identification of different long chain primary alcohols (LCOHs) of the general formula R-OH, wherein R is a long, unbranched, unsubstituted, linear aliphatic group. LCOHs have been reported as components of lepidopteran pheromone blends, but their phagodeterrent effect to aphids is herein reported for the first time. The effects of LCOHs on R. padi were studied by behavioral and electrophysiological bioassays. Feeding preference tests that were carried out with winged and wingless morphs of R. padi showed that LCOHs had high phagodeterrent activity and restrained aphids from settling on treated leaves at a concentration as low as 0.15 mM (0.036 g/l). The results of different electrophysiological analyses indicated that taste receptor neurons located on the aphid tarsomeres were involved in the LCOHs perception. Behavioral assays carried out with some commercial agrochemicals, including azadirachtin A, pyrethrum and a mineral oil-based product, in combination with 1-hexadecanol, the LCOH most abundantly produced by T. citrinoviride ITEM 4484, showed that these different active principles could be applied together, resulting in a useful increase of the phagodeterrent effect. The data shown indicate that these compounds can be profitably utilized for novel applications in biotechnical control of aphid pests. Furthermore, the tested LCOHs have no chiral centers and therefore can be obtained with good yield and at low cost through chemical synthesis, as well as from natural sources.

The absolute configuration of phytotoxins inuloxins B and C, produced by Inula viscosa, and with potential herbicidal activity for the management of parasitic plants, has been determined by Time-dependent density functional theory computational prediction of electronic circular dichroism and optical rotatory dispersion spectra. The inuloxin B has been converted to its 5-O-acetyl derivative, which due to its more constrained conformational features facilitated the computational analysis of its chiroptical properties. The analysis based on experimental and computed data led to assignment of absolute configuration to naturally occurring (+)-inuloxin B and (−)-inuloxin C as (7R,8R,10S,11S) and (5S,7S,8S,10S), respectively.

The absolute configuration of sphaeropsidin A was confirmed by X-ray analysis of the toxin and its 6- O - p -bromobenzoyl derivative. Sphaeropsidin A is a tetracyclic pimarane diterpene produced by different pathogens of forest plants belonging to Diplodia spp. This compound has been long known for its phytotoxic, antimicrobial, and insecticidal activities and, more recently, studied for its promising activity against drug-resistant melanoma and kidney cancer. These studies showed that sphaeropsidin A can overcome apoptosis and multidrug resistance in cancer cells through the modulation of ion-transporter activity, which is an emerging approach to cancer treatment. The availability of sphaeropsidin’s X-ray crystal structure could facilitate its further chemical and biological studies in pursuit of its development as an anticancer agent.