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The phytotoxic exopolysaccharides produced by Pseudomonas syringae pv. actinidiae, the causal agent of bacterial canker of kiwifruit, were isolated and partially identified. Their phytotoxic activity was evaluated on host and non-host plants and their role in the complex mechanisms of host-pathogen interaction was also discussed. The phytotoxic exopolysaccharides, which are natural antigens, were used to arise specific antibodies by rat immunization. The antibodies were used to develop a rapid and specific method to unambiguously detect P.s. pv. actinidiae exopolysaccharides isolated from bacterial culture and infected plant samples. Indeed, the antibodies recognized the exopolysaccharides produced by other two strains of P. s. pv. actinidiae but did not cross reacted with those isolated from P. s. pv. syringae and Pseudomonas viridiflava culture filtrates. Finally, the same antibodies significantly recognized the exopolysaccharides extracted from infected kiwi leaves. [ABSTRACT FROM AUTHOR]

Recently oxysporone, a phytotoxic dihydrofuropyranone, was isolated along with two closely related compounds, afritoxinones A and B, from liquid cultures of Diplodia africana , an invasive fungal pathogen of Phoenicean juniper. In this study, eight derivatives were hemisynthesized and assayed for their phytotoxic and antifungal activities in comparison to the parent compound. Each compound was tested on non-host plants and on four destructive plant pathogens such as Athelia rolfsii , Diplodia corticola , Phytophthora cinnamomi and P. plurivora. The results on the phytotoxic activity showed that the dihydrofuropyranone carbon skeleton and both the double bond the hydroxy group of dihydropyran ring appeared to be structural features important in conferring activity. Although the data concerning the antifungal activity did not allow to extract any structure–activity relationships, it should be underlined that the conversion of oxysporone into the corresponding 4- O -benzoyl derivative led to a compound showing a good antifungal activity towards three out of the four organisms tested. [ABSTRACT FROM AUTHOR]

Abstract: Sphaeropsidins A (1), B (7) and C (10), three fungal phytotoxins, unrearranged pimarane diterpenes produced by Diplodia cupressi and 10 semisynthetic derivatives were evaluated for their in vitro anticancer activities. Among these 13 compounds, sphaeropsidin A and two derivatives (2 and 6) thereof display 50% growth-inhibitory concentration in the low micromolar range for all cell lines analyzed. Structure activity relationship paralleled the phytopathogenic and antimicrobial ones except regarding the vinyl group at C-13 that does not seems to be required as it is for their antipathogenic activity. [Copyright &y& Elsevier]

Abstract: Two phytotoxic dihydrofuropyran-2-ones, named afritoxinones A and B, were isolated from liquid culture of Diplodia africana, a fungal pathogen responsible for branch dieback of Phoenicean juniper in Italy. Additionally, six others known metabolites were isolated and characterized: oxysporone, sphaeropsidin A, epi-sphaeropsidone, R-(−)-mellein, (3R,4R)-4-hydroxymellein and (3R,4S)-4-hydroxymellein. The structures of afritoxinones A and B were established by spectroscopic and optical methods and determined to be as (3aS ∗,6R ∗,7aS)-6-methoxy-3a,7a-dihydro-3H,6H-furo[2,3-b]pyran-2-one and (3aR ∗,6R ∗,7aS)-6-methoxy-3a,7a-dihydro-3H,6H-furo[2,3-b]pyran-2-one, respectively. The phytotoxic activity of afritoxinones A and B and oxysporone was evaluated on host (Phoenicean juniper) and non-host plant (holm oak, cork oak and tomato) by cutting and leaf puncture assay. Oxysporone proved to be the most phytotoxic compound. This study represents the first report of secondary metabolites produced by D. africana. In addition, the taxonomic implications of secondary metabolites in Botryosphaeriaceae family studies are discussed. [Copyright &y& Elsevier]

Abstract: Phoma exigua var. exigua, a fungal pathogen isolated from Cirsium arvense and Sonchus arvensis, proposed as a biocontrol agent of this noxious perennial weeds, produces in liquid and solid cultures different phytotoxic metabolites with potential herbicidal activity. The phytotoxic cytochalasins B, F, Z2, and Z3 and deoxaphomin were previously identified together with p-hydroxybenzaldehyde. Using spectroscopic methods, four new cytochalasins, termed phomachalasins A–D, were isolated and characterized as three new closely related 26-oxa[16] and one new [15]cytochalasans. They belong to a new subgroup of cytochalasans bearing a 1,2,3,4,6,7-hexasubstituted bicycle[3.2.0]heptene joined to the macrocyclic ring. None of the four new metabolites showed phytotoxic or antimicrobial activity. The lack of both phytotoxic and antimicrobial activities showed by all phomachalasins A–D was probably due to the strong modification of both functionalities and conformational freedom of the macrocyclic ring caused by its junction with the bulky and quite rigid new bicycle, namely bicycle[3.2.0]heptene. [Copyright &y& Elsevier]

Abstract: Two new strigolactone-like metabolites, named peagol and peagoldione, with germinative activity for root parasitic plants, were isolated from pea root exudates and were characterized by spectroscopic methods. Peagol was more active on Orobanche foetida and Phelipanche aegyptiaca seeds, while peagoldione was active on P. aegyptiaca only. Low activity was found on Orobanche crenata and Orobanche minor. Stimulatory activity of peagol on O. foetida seeds is most relevant as this species does not respond to the synthetic strigolactone analogue GR24, usually used as Orobanche germination standard. [Copyright &y& Elsevier]

Abstract: Phyllosticta cirsii, a fungal pathogen isolated from Cirsium arvense and proposed as biocontrol agent of this noxious perennial weed, produces in liquid cultures different phytotoxic metabolites with potential herbicidal activity. Four new oxazatricycloalkenones, named phyllostictines A–D, were isolated and characterized using essentially spectroscopic and chemical methods. Tested by leaf-puncture assay on the fungal host plant phyllostictine A proved to be highly toxic. The phytotoxicity decreases when both the dimension and the conformational freedom of the macrocyclic ring change, as in phyllostictines B and D, and it is totally lost when also the functionalization of the same ring is modified, as in phyllostictine C. Beside its phytotoxic properties, phyllostictine A has no antifungal activity, an interesting antibiotic activity only against Gram+ bacteria, and a noticeable zootoxic activity when tested at high concentrations. The integrity of the oxazatricycloalkenone system appears to be an important feature to preserve these activities. [Copyright &y& Elsevier]

Abstract: Orobanche crenata is a major threat to grain legume production. Fenugreek (Trigonella foenum-graecum) is an annual legume that has been shown to effectively reduce O. crenata infection when intercropped with grain legumes. In this paper, we point that this can be attributed to allelopathy, through inhibition of the germination of O. crenata by fenugreek root exudates. The main inhibitory metabolite was isolated and characterized. Allelopathy was demonstrated in different bioassays, by inhibition of O. crenata seeds germination both by growing fenugreek and pea plants together (intercropped), and by application of fenugreek root exudates. Fenugreek root exudates were extracted with organic solvent and fractionated giving several fractions, two of which showed moderate (27%) and strong (54%) inhibition of O. crenata seed germination, respectively. The most active metabolite is a new monosubstituted trioxazonane, characterized by spectroscopic methods as the 2-butyl-[1,4,7,2]trioxazonane and named trigoxazonane. [Copyright &y& Elsevier]

Abstract: Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report. [Copyright &y& Elsevier]

Abstract: A phytotoxic trisubstituted 2,4-pyridione, named sapinopyridione, was isolated from the culture filtrates of Sphaeropsis sapinea, a fungal pathogen of conifers occurring world-wide. Three strains were isolated from two cypress species. Strain D-55 isolated from Cupressus sempervirens resulted high producer of sapinopyridione (12.3mgl−1), whereas strain D-54 isolated from the same cypress species was low producer (1.1mgl−1); strain D-50 isolated from C. macrocarpa was intermediate producer (5.4mgl−1). Sapinopyridione was characterised by spectroscopic and chemical methods, as the 6-methyl-2-(2-methyl-1-oxobutyl)-1-oxa-5-azaspiro[2.5]oct-6-ene-4,8-dione. The structure was supported by the preparation of three key derivatives, whose phytotoxic and antimycotic activities were also tested on host plants and on three Seiridium species, virulent fungal agents of cypress canker disease. Some structure–activity relationships were identified for both phytoxicity and antifungal activities. These activities appear related to the presence of both pyridione and oxiran rings. Also the carbonyl group of the side chain seems to play a role into impart activity. [Copyright &y& Elsevier]

Abstract: A structure–activity relationship study was conducted assaying 25 natural analogues and derivatives of fusicoccin (FC), and cotylenol, the aglycone of cotylenins, for their ability to stimulate the seed germination of the parasitic species Orobanche ramosa. Some of the compounds tested proved to be highly active, being 8,9-isopropylidene of the corresponding FC aglycone and the dideacetyl derivative the most active FC derivatives. In both groups of glucosides and aglycones (including cotylenol), the most important structural feature to impart activity appears to be the presence of the primary hydroxy group at C-19. Furthermore, the functionalities and the conformation of the carbotricyclic ring proved to play a significant role. The dideacetyl derivative of FC, being easily and rapidly obtainable in high yield starting by FC, could be of interest for its practical application as a stimulant of Orobanche ramosa seed germination, inducing the “suicidal germination”, an interesting approach for parasitic plant management. [Copyright &y& Elsevier]

Abstract: When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro-1H-naphtho[2′,3′:4,5]furo[2,3-b]azepin-2-one. Assayed at 2μgμl−1 solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide. [Copyright &y& Elsevier]

A new lycorine-type alkaloid, named (-)-amarbellisine, was isolated from the bulbs of Egyptian Amaryllis belladonna L. together with the well known alkaloids (-)-lycorine, (-)-pancracine, (+)-vittatine, (+)-11-hydroxyvittatine, and (+)-hippeastrine. The new alkaloid, containing the pyrrolo[de]phenanthridine ring system, was essentially characterised by spectroscopic and optical methods, and proved to be the 2-methoxy-3a,4,5,7,11b,11c-hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridinol.By using HPTLC technique we also carried out a comparative study of the relative and total alkaloidal content at two different stages of plant growth. Finally, the antimicrobial activity of the isolated alkaloids was assayed. [Copyright &y& Elsevier]

A new phytotoxic enol tautomer of 4-pyridylpyruvic acid, named ascosonchine, was isolated from the culture filtrate of Ascochyta sonchi. Such a leaf pathogen is a potential biocontrol agent of Sonchus arvensis, a perennial herbaceous weed occurring throughout the temperate regions of the world. Ascosonchine, characterised as (Z)-2-hydroxy-3-(4-pyridyl)-2-propenoic acid by spectroscopic methods, showed selective herbicidal properties, that are not associated with antibacterial, antifungal or zootoxic activities. [Copyright &y& Elsevier]

Preliminary results on the structure of a novel sugar from a lipopolysaccharide from Pseudomonas corrugata, a plant pathogenic bacterium whose several aspects of phytopathogenic mechanism are under investigation, are described. This is a 5,7-diamino-5,7,9-trideoxynon-2-ulosonic acid, isolated as an O-glycoside from the Smith degradation of the O-chain. The structure was obtained both with NMR and MS methodologies. To the best of our knowledge, this is the first example of 3-hydroxylated non-2-ulosonic acid. [Copyright &y& Elsevier]

Three new cytochalasans, named cytochalasins Z1, Z2 and Z3, were isolated from the wheat culture of Pyrenophora semeniperda, a fungus proposed to biologically control grass weeds. Other cytochalasins isolated from the same organic extract were identified as the already known cytochalasins F, T, deoxaphomin and cytochalasins B, the latter being produced in very large amounts. All three new cytochalasins were characterized as 24-oxa[14]cytochalasans by extensive use of NMR and MS techniques. Cytochalasins Z1 and Z2 proved to be structurally related to cytochalasin T, whereas cytochalasin Z3 was related to cytochalasin B. When assayed on wheat and tomato seedlings, cytochalasin Z3, in comparison to the new cytochalasins, cytochalasin B, its 21,22-dihydroderivative, cytochalasin F and deoxaphomin showed a remarkable ability to inhibit root elongation. The possibility of using these metabolites in biological control strategies is discussed. [Copyright &y& Elsevier]

An O-specific polysaccharide containing 2-acetamidino-2-deoxy-β-d-glucopyranose (Glcp2Am), 2,4-diacetamido-2,4,6-trideoxy-β-d-glucopyranose (QuipNAc4NAc, bacillosamine) and 2,4-di-(N-acetyl-l-alanylamino)-2,4,6-trideoxy-β-d-glucopyranose (QuipNAlaAc4NAlaAc) was isolated from the phenol-soluble lipopolysaccharide fraction of the mushroom-associated bacterium Pseudomonas reactans. The structure, determined by means of chemical analysis and 1D and 2D NMR spectroscopy, showed a linear trisaccharide-repeating unit, as shown below:→3)-β-d-QuipNAlaAc4NAlaAc-(1→3)-α-d-Glcp2Am-(1→3)-α-d-QuipNAc4NAc(1→To our knowledge, this is the first complete O-chain structure reported for the lipopolysaccharide of a mushroom-associated bacterium. [Copyright &y& Elsevier]

Graphical abstract Abstract 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reaction of ophiobolin A with alcohols under acid catalysis was studied. • The reaction of ophiobolin A with alcohols gave acetals, hemiacetals and enol ethers. • Ophiobolin acid sensitive analogues displayed submicromolar antiproliferative potencies against GSCs cultured under the conditions of low pH of 6.5, representing the microenvironment to which GSCs are exposed in the clinic. • Several analogues showed good selectivity for inhibiting the proliferation of GSCs at pH of 6.5 as compared to pH of 7.5, indicating their potential to be selective for cancer tissue and particularly for eliminating GSCs. Glioblastoma (GBM) is the most common form of malignant primary brain tumor and is one of the most lethal cancers. The difficulty in treating GBM stems from its highly developed mechanisms of drug resistance. Our research team has recently identified the fungal secondary metabolite ophiobolin A (OpA) as an agent with significant activity against drug-resistant GBM cells. However, the OpA's mode of action is likely based on covalent modification of its intracellular target(s) and thus possible off-target reactivity needs to be addressed. This work involves the investigation of an acid-sensitive OpA analogue approach that exploits the elevated acidity of the GBM microenvironment to enhance the selectivity for tumor targeting. This project identified analogues that showed selectivity at killing GBM cells grown in cultures at reduced pH compared to those maintained under normal neutral conditions. These studies are expected to facilitate the development of OpA as an anti-GBM agent by investigating its potential use in an acid-sensitive analogue form with enhanced selectivity for tumor targeting. [ABSTRACT FROM AUTHOR]

Abstract: A putative capsular polysaccharide containing d-rhamnose was isolated from the phytopathogenic bacterium Burkholderia gladioli pv. agaricicola by phenol/water extraction followed by ultracentrifugation of the separated water phase and gel-permeation chromatography of the thus obtained supernatant. By means of chemical analyses and NMR spectroscopy, the repeating unit of the polymer was shown to be a linear tetrasaccharide with the structure.▪ [Copyright &y& Elsevier]

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-Man p NAc-(1 → 3)-β- l -Rha p -(1 → 4)-β-D-Glc p -(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. • Unique O -chain (OPS) structure of Pseudomonas donghuensis (Pd) lipopolysaccharide (LPS) • First report on the antifungal activityof Pd LPS/OPS against Macrophomina phaseolina • The OPS showed a repeating unit constituted by α-ManNAc, β-Rha and β-Glc [ABSTRACT FROM AUTHOR]

Abstract 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-4 H -xanthene-1,9-dione. Its relative stereochemistry was deduced by single crystal X-ray analysis while the absolute configuration was assigned as 4 S ,4a S ,9a S 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 IC 50 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 IC 50 35 μg/mL. Graphical abstract From the endolichenic fungus Talaromyces funiculosus a substituted dihydro-xanthene-1,9-dione, named funiculosone showing antimicrobial activity, was isolated. Image 1 Highlights • A substituted dihydro-xanthene-1,9-dione named funiculosone was isolated from an endolichenic fungus. • Other two known metabolites were isolated and identified as mangrovamide J and ravenelin. • All the compounds displayed antibacterial activity against Escherichia coli and Staphylococcus aureus. • Funiculosone also showed anticandidal activity against Candida albicans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Jonquailine, a new alkaloid recently isolated from Narcissus jonquilla quail , an Amaryllidaceae species cultivated for its flowers fragrance in Europe and USA, shows very significant anti-proliferative activity against several malignant cancer cell types. Although it was reported that this activity is related to the functionalities and to its stereochemistry at C-8 of B ring, the absolute configuration at this stereocenter was not known. Density functional theory (DFT) calculations of chiroptical properties, namely electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD) are employed here to complete assignment of absolute configuration of jonquailine, and then, by extension, to its analogues pretazettine and 8- O -methylpretazettine. While ECD is not discriminating and ORD is of limited use, VCD reveals decisive in the task of absolute configuration assignment. [ABSTRACT FROM AUTHOR]

The first asymmetric total synthesis of both enantiomers of the natural products colletorin A and colletochlorin A is presented. The proposed methodology is based on the coupling reaction between highly substituted aromatic Gilman cuprates and optically active allyl bromides, in turn obtained by Sharpless asymmetric dihydroxylation. The latter ensured a high degree of regio- and stereocontrol in the enantioselective step of the synthesis. The same synthetic strategy has been also applied for the preparation of differently halogenated synthetic analogues of colletochlorin A in high enantiomeric purity. The enantioselective synthesis of colletorin A and colletochlorin A allows to reliably assign their absolute configuration. Preliminary assessment of their herbicidal and insecticidal properties evidence the possibility to modulate the bioactivity of these compounds, highlighting its dependence on both the absolute stereochemistry and the halogen nature. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In a search of small molecules active against apoptosis-resistant cancer cells, a skeletal rearrangement of alkaloid haemanthamine was utilized to generate a series of compounds possessing the alkaloid montanine ring system. The synthesized compounds were found to inhibit proliferation of cancer cells resistant to apoptosis at micromolar concentrations. Selected compounds were also active against patient-derived glioblastoma cells expressing stem-cell markers. This is the first report describing the preparation of synthetic analogues of the montanine-type alkaloids with antiproliferative activity. The compounds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with poor prognoses. [ABSTRACT FROM AUTHOR]

Uncaria tomentosa (Willd.) DC. (Rubiacee), also known as uña de gato , is a plant that grows wild in the upper Amazon region of Peru and has been widely used in folk medicine to treat several health conditions including cancer. We have produced an aqueous extract from Uncaria tomentosa (UT-ex) and analyzed its effects on squamous carcinoma cells and immortalized HaCaT keratinocytes. Squamous cell carcinoma (SCC) is an uncontrolled growth of abnormal cells arising in the skin's squamous layer of epidermis. When detected at an early stage, SCCs are almost curable, however, if left untreated, they can penetrate the underlying tissue and become disfiguring. We have evaluated cell proliferation, apoptosis and the level of reactive oxygen species following UT-ex treatment. UT-ex affected cell cycle progression and reduced cell viability in a dose and time-dependent manner. From a mechanistic point of view, this delay in cell growth coincided with the increase of reactive oxygen species (ROS). Furthermore, PARP1 cleavage was associated to the reduction of Y-box binding protein 1 (YB-1) 36 kDa, a nuclear prosurvival factor involved in DNA damage repair. These data indicate that UT-ex-induced cell death can be ascribed, at least in part, to its ability both to induce oxidative DNA damage and antagonize the mechanism of DNA repair relying upon YB-1 activity. They also show that non metastatic SCCs are more susceptible to UT-ex treatment than untransformed keratinocytes supporting the use of UT-ex for the treatment of precancerous and early forms of squamous cell carcinomas. Preliminary chemical investigation of UT-ex revealed the presence of hydrophilic low-medium molecular weight metabolites with anticancer potential towards squamous carcinoma cells. [ABSTRACT FROM AUTHOR]

A new tetrasubstituted indolylidenepyrandione named colletopyrandione ( 1 ), together with a tetrasubstituted chroman- and a tetrasubstituted isocroman-3,5-diol, named colletochlorins G and H ( 2 , 3 ), respectively, were isolated from the culture filtrates of the fungus Colletotrichum higginsianum together with the already known colletochlorin A, 4-chloroorcinol, colletopyrone and colletochlorins E and F. Colletopyrandione and the two new colletochlorins (G and H) were characterized as ( Z )-3-(3-hydroxy-3-methylindolin-2-ylidene)-5,6-dimethyl-pyran-2,4-dione, 8-chloro-2,2,7-trimethylchroman-3,5-diol and 8-chloro-1,1,7-trimethylisochroman-3,5-diol, respectively, by spectroscopic (NMR and HRESIMS) methods. The relative configuration of 1 was assigned by X-ray diffractometric analysis. Colletopyrandione was isolated as scalemic mixture and the absolute configuration of the most abundant enantiomer was assigned by ECD and VCD spectra combined with quantum-mechanical calculations. Assayed in several biological systems, colletopyrandione showed a modest phytotoxic activity, associated to a complete lack of toxicity towards off-target organisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pseudomonas chlororaphis subsp. aureofaciens encompasses bacterial strains that effectively control phytopathogenic fungi through the production of the natural antibiotics named phenazines. In this work, the involvement of phenazine production in the interaction between the biological control agent P. chlororaphis subsp. aureofaciens M71 and the fungus Seiridium cardinale , a serious cypress pathogen, was investigated. Field trials were carried out to assess the role of phenazines in the control of S. cardinale in vivo . Results showed that P. chlororaphis subsp. aureofaciens M71 and 30-84, both able to produce phenazine-1-carboxylic acid (PCA), drastically reduced the canker development incited by S. cardinale . Conversely, strain M71b, a natural gacA mutant of P. chlororaphis subsp. aureofaciens M71, showed a decrease in PCA production and a reduction in controlling S. cardinale . These results were enforced by the reduction of canker size higher than 94% registered when 6 μg of pure PCA was directly applied on each cypress wound. Furthermore, PCA was detected in cypress plant tissues only when P. chlororaphis subsp. aureofaciens M71 was interacting with S. cardinale for 30 days. All these data support that the biological control of S. cardinale achieved by the application of P. chlororaphis subsp. aureofaciens M71 relies mainly on the ability of the bacterial strain to produce PCA in planta . [ABSTRACT FROM AUTHOR]

A new mesembrine-type alkaloid, named sarniensine, was isolated together with tazettine, lycorine, the main alkaloid, and 3-epimacronine from Nerine sarniensis , with the last two produced for the first time by this plant. This Amaryllidaceae, which is indigenous of South Africa, was investigated for its alkaloid content, because the organic extract of its bulbs showed strong larvicidal activity with an LC 50 value of 0.008 μg μL − 1 against first instar Aedes aegypti larvae and with an LD 50 value 4.6 μg/mosquito against adult female Ae. aegypti, which is the major vector for dengue, yellow fever and the Zika virus. The extract did not show repellency at MED value of 0.375 mg cm 2 against adult Ae. aegypti . Sarniensine was characterized using spectroscopic and chiroptical methods as (3a R ,4 Z ,6 S ,7a S )-6-methoxy-3a-(2′-methoxymethyl-benzo [1,3]dioxol-1'-yl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1 H -indole. It was less effective against larva at the lowest concentration of 0.1 μg μL − 1 , however it showed strong adulticidal activity with an LD 50 value of 1.38 ± 0.056 μg mosquito − 1 . [ABSTRACT FROM AUTHOR]

Two new furopyrans, named chenopodolans E and F ( 1 and 2 ), were isolated from the liquid culture of Phoma chenopodiicola , a fungal pathogen proposed for the biological control of Chenopodium album , a common worldwide weed of arable crops. They were characterized using spectroscopic methods as 3-(3-methoxy-2,6-dimethyl-7a H -furo[2,3 b ]pyran-4-yl)-but-2-enoic acid methyl ester and 1-(3-methoxy-2,6-dimethyl-7a H -furo[2,3 b ]pyran-4-yl)-ethanone, respectively. Furthermore, the absolute configuration of chenopodolan B ( 3 ) was established to be (7a R ,9 S ) by a combined application of the advanced Mosher's method and of quantum mechanical calculations of chiroptical (ECD and ORD) properties. When 1 and 2 were assayed on punctured leaves at 2 μg/μL, only 2 was active on Sonchus arvensis while 1 caused around 75% larval mortality on Artemia salina larvae at 0.1 μg/μL. [ABSTRACT FROM AUTHOR]

A new nor- pimarane diterpene and a new monosubstituted bifuranylone, named sphaeropsidin G ( 1 ) and diplobifuranylone D ( 2 ), were isolated from the organic extract of Diplodia corticola an oak pathogen together with the already known 4-hydroxyscytalone ( 3 ) and diorcinol ( 4 ). Sphaeropsidin G and diplobifuranylone D were characterized by using spectroscopic methods as 1,1,7-trimethyl-7-vinyl-2,3,4,4a,4b,5,6,7,10,10a-decahydro-1 H -phenanthren-9-one and 5′-(1-hydroxyethyl)-2′,5′-dihydro-2 H -[2,2′]bifuranyl-5-one, respectively. The relative configurations of sphaeropsidin G and diplobifuranylone D were assigned by comparison of their spectroscopic properties with those of sphaeropsidin A and diplobifuranylones A–C and confirmed by NOESY spectra. Each compound was tested for phytotoxic, antifungal, antioomycetes and zootoxic activity. Compound 4 was active in all bioassays exhibiting remarkable phytotoxicity on Quercus afares , Quercus suber , Quercus ilex and Celtis australis leaves at 1 mg/mL causing necrotic lesions. It completely inhibited the mycelial growth of Athelia rolfsii , Lasiodiplodia mediterranea and Phytophthora cinnamomi . In the Artemia salina assay, 1 , 3 and 4 proved to be active, while 2 was found to be inactive in all bioassays. [ABSTRACT FROM AUTHOR]

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 (7 R ,8 R ,10 S ,11 S ) and (5 S ,7 S ,8 S ,10 S ), respectively. [ABSTRACT FROM AUTHOR]

An undescribed disubstituted dihydrofuranone, named diplofuranoxin, was isolated, together with the six well known metabolites sphaeropsidins A and C, epi -sphaeropsidone, mellein and cis - and trans -4-hydroxymelleins, from the fungal species Diplodia subglobosa , an emerging pathogen involved in the ash dieback aetiology in Europe. Currently, the disease represents the main threat to European ash heritage and the wood associated industry. Diplofuranoxin, was characterized essentially by NMR and HRESIMS spectra as (3Z)-3-(2,3-dihydroxybutylidene)-5-methyldihydrofuran-2(3 H)-one. Its relative and absolute configuration was determined by joining NOESY NMR experiments and computational analysis of electronic circular dichroism spectrum. All the metabolites were screened for phytotoxic, antioomycetes and zootoxic activities and only sphaeropsidin A and epi -sphaeropsidone were active in two out of three bioassays performed. In addition, sphaeropsidin A completely inhibited mycelium growth of Phytophthora cambivora , whereas the inhibition rate of epi -sphaeropsidone was less than 50% at the higher concentration used. Both metabolites were inactive in the Artemia salina assay. Results obtained in this study have allowed to characterize for the first time the main metabolites produced in vitro by D. subglobosa and to increase the knowledge on the metabolic profile of Botryosphaeriaceae for a correct taxonomic classification of the strains belonging to this family. [Display omitted] • Diplodia subglobosa is the causal agent of ash diseases. • A disubstituted dihydrofuranone was isolated from its culture filtrates. • It was characterized by NMR and HRESIMS spectra and named diplofuranoxin. • Other six phytotoxins were isolated and identified. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A new 19-oxa-tricyclohenicosatetraenone and a new dioxacyclopropacycloundecene-10-carboaldehyde and its 6,7-dihydro derivative, named saponaroxins A–C, were isolated from the culture filtrate of Alternaria saponariae a fungal pathogen of the well-known medicinal plant Saponaria officinalis . Saponaroxins A–C were characterized by spectroscopic methods. When assayed on punctured leaf segments of two weeds, Sonchus arvensis and Elytrigia repens saponaroxins B–C were found to be phytotoxic. They demonstrated moderate antimicrobial activity and low toxicity against Paramecium caudatum . Saponaroxin A was acutely toxic to P. caudatum while showed no phytotoxic nor antimicrobial activity. [ABSTRACT FROM AUTHOR]

Impatiens glandulifera has been imported from Himalaya in Europe and is considered as an invasive alien plant whose spreading arouses increasing interest among scientific literature. Via anti-cancer bioguiding, two new glucosylated steroids, named glanduliferins A and B, were isolated from the dried stem of I. glandulifera plants, together with the well-known α-spinasterol and 2-methoxy-1,4-naphthoquinone, which are also isolated from roots and leaves. They were characterized as 17-(2-hydroxy-2-pentamethylcyclopropyl-ethyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1 H -cyclopents[ a ]phenathren-3- O -(4- O -acetyl)-α- d -glucopyranoside and 17-(4-ethyl-1,5-dimethyl-hex-2-enyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1 H -cyclopents[ a ]phenathren-3- O -(6- O -acetyl)-β-D-glucopyranoside using various NMR and HRESIMS techniques and chemical methods. In vitro determination of the growth inhibitory activity of the four isolated compounds using the MTT colorimetric assay revealed mean IC 50 growth inhibitory value of ~ 30 μM for glanduliferin A while glanduliferin B and α-spinasterol were poorly active till 100 μM. 2-methoxy-1,4-naphthoquinone revealed to be active in the single micromolar digit range as previously described. Quantitative videomicroscopy analyses of the effects of glanduliferins A and B suggested cytostatic rather than cytotoxic activity in U373 glioblastoma (GBM) cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most common form of malignant primary brain tumor, is characterized by resistance to apoptosis, which is largely responsible for the low effectiveness of the classical chemotherapeutic approaches based on apoptosis induction in cancer cells. Previously, a fungal secondary metabolite ophiobolin A was found to have significant activity against apoptosis-resistant glioblastoma cells through the induction of a non-apoptotic cell death, thus, offering an innovative strategy to combat this type of cancer. The current work describes the results of a preliminary evaluation of ophiobolin A in an in vivo glioblastoma model and its chemical derivatization to establish first synthetically generated structure–activity relationship. The synthetic work has also led to the discovery of a unique reaction of ophiobolin A with primary amines suggesting the possibility of pyrrolylation of lysine residues on its intracellular target protein(s). [ABSTRACT FROM AUTHOR]

Two phytotoxins were isolated from the liquid culture of Phoma chenopodiicola , a fungal pathogen proposed for the biological control of Chenopodium album , a common worldwide weed of arable crops. The two phytotoxins appeared to be a new tetrasubstituted furopyran and a new ent- pimaradiene. From the same culture a new tetrasubstituted isocoumarin was also isolated. These compounds were characterized by using spectroscopic (essentially 1D and 2D NMR and HR ESI MS) and chemical methods as 3-(3-methoxy-2,6-dimethyl-7a H -furo[2,3- b ]pyran-4-yl)-but-2-en-1-ol (chenopodolan D, 1 ) (1 S ,2 S ,3 S ,4 S ,5 S ,9 R ,10 S ,12 S ,13 S )-1,3,12-triacetoxy-2,hydroxy-6-oxo- ent -pimara-7(8),15-dien-18-oic acid 2,18-lactone (chenopodolin B, 3 ), and, 4,5,7-trihydroxy-3-methyl-isochroman-1-one (chenisocoumarin, 2 ) The absolute configuration of chenisocoumarin was assigned by applying an advanced Mosher’s method through the derivatization of its secondary hydroxylated carbon C-4, while that of chenopodolan D by application of quantum mechanical calculations of chiroptical (ECD and ORD) properties. When assayed by leaf puncture against non-host weeds, chenopodolan D and chenopodolin B showed phytotoxicity while chenisocoumarin and the 9- O -acetyl derivative of chenopodolan D were inactive. These results confirm that the nature of the side chain at C-4 in chenopodolans, and in particular its hydroxylation, are important features for activity. The activity of chenopodolin B could also be explained by its possible hydrolysis to chenopodolin. [ABSTRACT FROM AUTHOR]

The absolute configuration (AC) of the plant phytotoxin inuloxin A, produced by Inula viscosa , and of the fungal phytotoxin seiricardine A, obtained from Seiridium fungi, pathogen for cypress, has been determined by experimental measurements and theoretical simulations of chiroptical properties of three related methods, namely, Optical Rotatory Dispersion (ORD), Electronic Circular Dichroism (ECD), and Vibrational Circular Dichroism (VCD). Computational prediction by Density Functional Theory (DFT) of VCD spectra and by Time-dependent DFT (TDDFT) of ORD and ECD spectra allowed to assign (7 R ,8 R ,10 S ) AC to naturally occurring (+)-inuloxin A. In the case of compound (−)-seiricardine A, which lacks useful for the analysis UV–Vis absorption, and thus provides a hardly detectable ECD spectrum and quite low ORD values, an introduction of a suitable chromophore by chemical derivatization was performed. The corresponding derivative, 2 -O-p -bromobenzoate ester, gave rise to an intense ECD spectrum and higher ORD and VCD values. The comparison of computed spectra with the experimental ones allowed to assign (1 S ,2 R ,3a S ,4 S ,5 R ,7a S ) AC to (−)-2- O - p -bromobenzoate ester of seiricardine A and then to (−)-seiricardine A. This study further supports a recent trend of concerted application of more than a single chiroptical technique toward an unambiguous assignment of AC of flexible and complex natural products. Moreover, the use of chemical derivatization, with insertion of suitable chromophoric moieties has allowed to treat also UV–Vis transparent molecules by ECD and ORD spectroscopies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Orobanche and Phelipanche species (the broomrapes) are root parasitic plants, some of which represent serious weed problems causing heavy yield losses on important crops. Current control relies on the use of certain agronomic practices, resistant crop varieties, and herbicides, albeit success has been marginal. Agronomic practices such as the use of allelopathic species in intercropping or cover crops, or the use of direct seedling over residues of allelopathic species incorporate the principle of allelopathy exerted by molecules exuded from roots or released by crop residues to control broomrapes. In addition, the isolation of natural substances from root exudates of plants with potential to inhibit broomrape development opens the door to the design of new herbicides based on natural and benign sources. Ryecyanatines A and B and ryecarbonitrilines A and B, the first new substituted cyanatophenol, substituted cyanatobenzo[1,3]dioxole, and the latter two new substituted benzo[1,3]dioxolecarbonitriles were isolated from rye ( Secale cereale L.) root exudates. They were characterized as 4-cyanato-2-methoxyphenol, 2-cyanato-benzo[1,3]dioxole, 2-methoxybenzo[1,3]dioxole-5-carbonitrile and benzo[1,3]dioxole-2-carbonitrile by spectroscopic (essentially NMR and HRESI MS spectra) methods. These compounds were investigated for allelopathic activity on Orobanche germination and development. Ryecarbonitriline A induced germination of Orobanche cumana seeds, and this germination can be considered as suicidal because O. cumana does not parasite rye roots and cannot survive without host resources beyond germination stage. In addition, ryecyanatine A promotes a rapid cessation of O. cumana , Orobanche crenata and Orobanche minor radicle growth with the promotion of a layer of papillae at the radicle tip in O. cumana and O. crenata hampering the contact of the parasite to the host. Ryecarbonitriline B also displayed the same activity although being less active than ryecyanatine A and mainly restricted to O. cumana . [ABSTRACT FROM AUTHOR]