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Lampedusa, the largest island of the Pelagie archipelago, Sicily, Italy, has proven to be a rich source of plants and shrubs used in folk medicine. These plants, often native to the island, have been very poorly investigated for their phytochemical composition and biological potential to be translated into pharmacological applications. To start achieving this purpose, a specimen of Limonium lopadusanum, a plant native to Lampedusa, was investigated for the first time. This manuscript reports the results of a preliminary biological assay, focused on antimicrobial activity, carried out using the plant organic extracts, and the isolation and chemical and biological characterization of the secondary metabolites obtained. Thus 3-hydroxy-4-methoxybenzoic acid methyl ester (syn: methyl isovanillate, (1), methyl syringate (2), pinoresinol (3), erythrinassinate C (4) and tyrosol palmitate (5) were isolated. Their antimicrobial activity was tested on several strains and compound 4 showed promising antibacterial activity against Enterococcus faecalis. Thus, this metabolite has antibiotic potential against the drug-resistant opportunistic pathogen E. faecalis. [ABSTRACT FROM AUTHOR]

Ascochyta blight, caused by Ascochyta fabae, poses a significant threat to faba bean and other legumes worldwide. Necrotic lesions on stems, leaves, and pods characterize the disease. Given the economic impact of this pathogen and the potential involvement of secondary metabolites in symptom development, a study was conducted to investigate the fungus's ability to produce bioactive metabolites that might contribute to its pathogenicity. For this investigation, the fungus was cultured in three substrates (Czapek-Dox, PDB, and rice). The produced metabolites were analyzed by NMR and LC-HRMS methods, resulting in the dereplication of seven metabolites, which varied with the cultural substrates. Ascochlorin, ascofuranol, and (R)-mevalonolactone were isolated from the Czapek-Dox extract; ascosalipyrone, benzoic acid, and tyrosol from the PDB extract; and ascosalitoxin and ascosalipyrone from the rice extract. The phytotoxicity of the pure metabolites was assessed at different concentrations on their primary hosts and related legumes. The fungal exudates displayed varying degrees of phytotoxicity, with the Czapek-Dox medium's exudate exhibiting the highest activity across almost all legumes tested. The species belonging to the genus Vicia spp. were the most susceptible, with faba bean being susceptible to all metabolites, at least at the highest concentration tested, as expected. In particular, ascosalitoxin and benzoic acid were the most phytotoxic in the tested condition and, as a consequence, expected to play an important role on necrosis's appearance. [ABSTRACT FROM AUTHOR]

Different fungal species belonging to the Colletotrichum genus cause anthracnose disease in a range of major crops, resulting in huge economic losses worldwide. Typical symptoms include dark, sunken lesions on leaves, stems, or fruits. Colletotrichum spp. have synthesized, in vitro, a number of biologically active and structurally unusual metabolites that are involved in their host's infection process. In this study, we applied a one strain many compounds (OSMAC) approach, integrated with targeted and non-targeted metabolomics profiling, to shed light on the secondary phytotoxic metabolite panels produced by pathogenic isolates of Colletotrichum truncatum and Colletotrichum trifolii. The phytotoxicity of the fungal crude extracts was also assessed on their primary hosts and related legumes, and the results correlated with the metabolite profile that arose from the different cultural conditions. To the best of our knowledge, this is the first time that the OSMAC strategy integrated with metabolomics approaches has been applied to Colletotrichum species involved in legume diseases. [ABSTRACT FROM AUTHOR]

The alkaloids are one of the most represented family of natural occurring biological active compounds. Amaryllidaceae are also very well known for their beautiful flower and are thus used as ornamental plants in historic and public gardens. The Amaryllidacea alkaloids constitute an important group that is subdivided into different subfamilies with different carbon skeletons. They are well known from ancient times for their long application in folk medicine, and in particular, Narcissus poeticus L. was known to Hippocrates of Cos (ca. B.C. 460–370), who treated uterine tumors with a formulate prepared from narcissus oil. To date, more than 600 alkaloids of 15 chemical groups exhibiting various biological activities have been isolated from the Amaryllidaceae plants. This plant genus is diffused in regions of Southern Africa, Andean South America and the Mediterranean basin. Thus, this review describes the chemical and biological activity of the alkaloids collected in these regions in the last two decades as weel those of isocarbostyls isolated from Amaryllidaceae in the same regions and same period. [ABSTRACT FROM AUTHOR]

Radicinin is a phytotoxic dihydropyranopyran-4,5-dione isolated from the culture filtrates of Cochliobolus australiensis, a phytopathogenic fungus of the invasive weed buffelgrass (Cenchrus ciliaris). Radicinin proved to have interesting potential as a natural herbicide. Being interested in elucidating the mechanism of action and considering radicinin is produced in small quantities by C. australiensis, we opted to use (±)-3-deoxyradicinin, a synthetic analogue of radicinin that is available in larger quantities and shows radicinin-like phytotoxic activities. To obtain information about subcellular targets and mechanism(s) of action of the toxin, the study was carried out by using tomato (Solanum lycopersicum L.), which, apart from its economic relevance, has become a model plant species for physiological and molecular studies. Results of biochemical assays showed that (±)-3-deoxyradicinin administration to leaves induced chlorosis, ion leakage, hydrogen peroxide production, and membrane lipid peroxidation. Remarkably, the compound determined the uncontrolled opening of stomata, which, in turn, resulted in plant wilting. Confocal microscopy analysis of protoplasts treated with (±)-3-deoxyradicinin ascertained that the toxin targeted chloroplasts, eliciting an overproduction of reactive singlet oxygen species. This oxidative stress status was related by qRT-PCR experiments to the activation of transcription of genes of a chloroplast-specific pathway of programmed cell death. [ABSTRACT FROM AUTHOR]

Weeds such as parasite plants are one of the most serious pests that farmers are forced to combat since the development of agriculture using different methods including mechanic and agronomy strategies. These pests have generated significant losses of agrarian and herding production, constituting a serious impediment for agricultural activities in reforestation practices and in important infrastructures. All these serious problems have induced the expansive and massive use of synthetic herbicides, which represents one of the main cause of environmental pollution, as well as serious risks for human and animal health. An alternative environmental friendly control method could be the use of bioherbicides based on suitably bioformulated natural products, of which the main ones are fungal phytotoxins. This review covers the literature from 1980 to the present (2022) and concerns fungal phytotoxins with potential herbicidal activity in order to obtain their efficacy as bioherbicides for practical application in agriculture. Furthermore, some bioherbicides based on microbial toxic metabolites are commercially available, and their application in field, mode of action and future perspectives are also discussed. [ABSTRACT FROM AUTHOR]

Fungal phytotoxins can be defined as secondary metabolites toxic to host plants and are believed to be involved in the symptoms developed of a number of plant diseases by targeting host cellular machineries or interfering with host immune responses. As any crop, legumes can be affected by a number of fungal diseases, causing severe yield losses worldwide. In this review, we report and discuss the isolation, chemical, and biological characterization of fungal phytotoxins produced by the most important necrotrophic fungi involved in legume diseases. Their possible role in plant–pathogen interaction and structure–toxicity relationship studies have also been reported and discussed. Moreover, multidisciplinary studies on other prominent biological activity conducted on reviewed phytotoxins are described. Finally, we explore the challenges in the identification of new fungal metabolites and their possible applications in future experiments. [ABSTRACT FROM AUTHOR]

Major threats to the human lifespan include cancer, infectious diseases, diabetes, mental degenerative conditions and also reduced agricultural productivity due to climate changes, together with new and more devastating plant diseases. From all of this, the need arises to find new biopesticides and new medicines. Plants and microorganisms are the most important sources for isolating new metabolites. Lampedusa Island host a rich contingent of endemic species and subspecies. Seven plant species spontaneously growing in Lampedusa, i.e., Atriplex halimus L. (Ap), Daucus lopadusanus Tineo (Dl), Echinops spinosus Fiori (Es) Glaucium flavum Crantz (Gf) Hypericum aegypticum L: (Ha), Periploca angustifolia Labill (Pa), and Prasium majus L. (Pm) were collected, assessed for their metabolite content, and evaluated for potential applications in agriculture and medicine. The HPLC-MS analysis of n-hexane (HE) and CH2Cl2 (MC) extracts and the residual aqueous phases (WR) showed the presence of several metabolites in both organic extracts. Crude HE and MC extracts from Dl and He significantly inhibited butyrylcholinesterase, as did WR from the extraction of Dl and Pa. HE and MC extracts showed a significant toxicity towards hepatocarcinoma Huh7, while Dl, Ha and Er HE extracts were the most potently cytotoxic to ileocecal colorectal adenocarcinoma HCT-8 cell lines. Most extracts showed antiviral activity. At the lowest concentration tested (1.56 μg/mL), Dl, Gf and Ap MC extracts inhibited betacoronavirus HCoV-OC43 infection by> 2 fold, while the n-hexane extract of Pm was the most potent. In addition, at 1.56 μg/mL, potent inhibition (>10 fold) of dengue virus was detected for Dl, Er, and Pm HE extracts, while Pa and Ap MC extracts dampened infections to undetectable levels. Regarding to phytotoxicity, MC extracts from Er, Ap and Pm were more effective in inhibiting tomato rootlet elongation; the same first two extracts also inhibited seed cress germination while its radicle elongation, due to high sensitivity, was affected by all the extracts. Es and Gf MC extracts also inhibited seed germination of Phelipanche ramosa. Thus, we have uncovered that many of these Lampedusa plants displayed promising biopesticide, antiviral, and biological properties. [ABSTRACT FROM AUTHOR]

Microorganisms, virus, weeds, parasitic plants, insects, and nematodes are among the enemies that induce severe economic losses to agrarian production. Farmers have been forced to combat these enemies using different methods, including mechanical and agronomic strategies, since the beginning of agriculture. The development of agriculture, due to an increased request for food production, which is a consequence to the rapid and noteworthy growth of the world's population, requires the use of more efficient methods to strongly elevate the yield production. Thus, in the last five-to-six decades, a massive and extensive use of chemicals has occurred in agriculture, resulting in heavy negative consequences, such as the increase in environmental pollution and risks for human and animal health. These problems increased with the repetition of treatments, which is due to resistance that natural enemies developed against this massive use of pesticides. There are new control strategies under investigation to develop products, namely biopesticides, with high efficacy and selectivity but based on natural products which are not toxic, and which are biodegradable in a short time. This review is focused on the microbial and plant metabolites with nematocidal activity with potential applications in suitable formulations in greenhouses and fields. [ABSTRACT FROM AUTHOR]

Araujia hortorum is a perennial vining plant species native to South America. It was introduced into many countries for ornamental and medicinal purposes as well as for its edible fruits, but it has become highly invasive, generating severe environmental problems. Biological control using bioherbicides and natural compounds is an interesting control option. The pathogenic fungus Ascochyta araujiae, isolated from infected leaves of A. hortorum, could be considered as a potential biocontrol agent. Its ability to produce bioactive metabolites was studied. The organic extract of the fungal culture filtrates showed interesting phytotoxic activities consisting of clearly visible necrotic symptoms (0.5–1 cm in diameter) in the punctured leaves. Thus, it was purified; this afforded three main metabolites. These were chemically and biologically characterised: one proved to be a new pentasubstituted dihydrofuro[3,2-b]furan-2(5H)-one, named araufuranone (1). The others were the already known fungal metabolites neovasinin and 2,4-dihydroxy-6-hydoxymethylbenzaldehyde (2 and 3). The structure of araufuranone was determined using spectroscopic methods (essentially 1D and 2D 1H and 13C NMR and HR ESIMS spectra); its relative configuration was assigned by a NOESY spectrum. To the best of our knowledge, araufuranone is the first example of a naturally occurring compound showing that carbon skeleton. Assayed by a puncture, araufuranone proved to be weakly active on the leaves of Diplotaxis sp. and Sonchus sp.; the other two metabolites were even less toxic. Tested on cress, compounds 2 and 3 were able to partially inhibit rootlet elongation whereas araufuranone was almost inactive. [ABSTRACT FROM AUTHOR]

Alkaloids isolated from members of the Amaryllidaceae plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates. [ABSTRACT FROM AUTHOR]

Alkaloids are a wide family of basic N-containing natural products, whose research has revealed bioactive compounds of pharmacological interest. Studies on these compounds have focused more attention on those produced by plants, although other types of organisms have also been proven to synthesize bioactive alkaloids, such as animals, marine organisms, bacteria, and fungi. This review covers the findings of the last 20 years (2002–2022) related to the isolation, structures, and biological activities of the alkaloids produced by mushrooms, a fungal subgroup, and their potential to develop drugs and agrochemicals. In some cases, the synthesis of the reviewed compounds and structure−activity relationship studies have been described. [ABSTRACT FROM AUTHOR]

Natural compounds have always represented an important source for new drugs. Although fungi represent one such viable source, to date, no fungal metabolite has been marketed as an anticancer drug. Based on our work with phytotoxins as potential chemical scaffolds and our recent findings involving three phytopathogenic fungi, i.e., Cochliobolus australiensis, Kalmusia variispora and Hymenoscyphus fraxineus, herein, we evaluate the in vitro anti-cancer activity of the metabolites of these fungi by MTT assays on three cancer cell models harboring various resistance levels to chemotherapeutic drugs. Radicinin, a phytotoxic dihydropyranopyran-4,5-dione produced by Cochliobolus australiensis, with great potential for the biocontrol of the invasive weed buffelgrass (Cenchrus ciliaris), showed significant anticancer activity in the micromolar range. Furthermore, a SAR study was carried out using radicinin, some natural analogues and hemisynthetic derivatives prepared by synthetic methods developed as part of work aimed at the potential application of these molecules as bioherbicides. This investigation opens new avenues for the design and synthesis of novel radicinin analogues as potential anticancer agents. [ABSTRACT FROM AUTHOR]

The antibiotic and nematocidal activities of extracts from two coastal lichen species collected on Lampedusa Island (Sicily), Ramalina implexa Nyl. and Roccella phycopsis Ach., were tested. Methyl orsellinate, orcinol, (+)-montagnetol, and for the first time 4-chlororcinol were isolated from Roccella phycopsis. (+)-Usnic acid was obtained from Ramalina implexa. The crude organic extract of both lichen species showed strong antibiotic activity against some bacterial species and nematocidal activity. Among all the pure metabolites tested against the infective juveniles (J2) of the root-knot nematode (RKN) Meloydogine incognita, (+)-usnic acid, orcinol, and (+)-montagnetol had significant nematocidal activity, comparable with that of the commercial nematocide Velum® Prime, and thus they showed potential application in agriculture as a biopesticide. On the contrary, methyl orsellinate and 4-chlororcinol had no nematocidal effect. These results suggest that the substituent pattern at ortho-para-position in respect to both hydroxyl groups of resorcine moiety, which is present in all metabolites, seems very important for nematocidal activity. The organic extracts of both lichens were also tested against some Gram-positive and Gram-negative bacteria. Both extracts were active against Gram-positive species. The extract of Ramalina implexa showed, among Gram-negative species, activity against Escherichia coli and Acinetobacter baumannii, while that from Roccella phycopsis was effective towards all test strains, with the exception of Pseudomonas aeruginosa. The antimicrobial activity of (+)-usnic acid, methyl orsellinate, and (+)-montagnetol is already known, so tests were focused on orcinol and 4-chlororcinol. The former showed antibacterial activity against all Gram positive and Gram-negative test strains, with the exception of A. baumannii and K. pneumoniae, while the latter exhibited a potent antibacterial activity against Gram-positive test strains and among Gram-negative strains, was effective against A. baumannii and K. pneumonia. These results suggest, for orcinol and 4-chlororcinol, an interesting antibiotic potential against both Gram-positive and Gram-negative bacterial strains. [ABSTRACT FROM AUTHOR]

Cyclopaldic acid is one of the main phytotoxic metabolites produced by fungal pathogens of the genus Seiridium, causal agents, among others, of the canker disease of plants of the Cupressaceae family. Previous studies showed that the metabolite can partially reproduce the symptoms of the infection and that it is toxic to different plant species, thereby proving to be a non-specific phytotoxin. Despite the remarkable biological effects of the compound, which revealed also insecticidal, fungicidal and herbicidal properties, information about its mode of action is still lacking. In this study, we investigated the effects of cyclopaldic acid in Arabidopsis thaliana plants and protoplasts, in order to get information about subcellular targets and mechanism of action. Results of biochemical assays showed that cyclopaldic acid induced leaf chlorosis, ion leakage, membrane-lipid peroxidation, hydrogen peroxide production, inhibited root proton extrusion in vivo and plasma membrane H+-ATPase activity in vitro. qRT-PCR experiments demonstrated that the toxin elicited the transcription of key regulators of the immune response to necrotrophic fungi, of hormone biosynthesis, as well as of genes involved in senescence and programmed cell death. Confocal microscopy analysis of protoplasts allowed to address the question of subcellular targets of the toxin. Cyclopaldic acid targeted the plasma membrane H+-ATPase, inducing depolarization of the transmembrane potential, mitochondria, disrupting the mitochondrial network and eliciting overproduction of reactive oxygen species, and vacuole, determining tonoplast disgregation and induction of vacuole-mediated programmed cell death and autophagy. [ABSTRACT FROM AUTHOR]

Biocides based on chemical synthetic compounds have been commonly used to counteract damages caused by microorganisms on stone cultural heritage. However, in the last few years, the use of commercial and traditional biocides has been banned and/or limited due to their dangerous profile for the environment, as well as human and animal health. Natural products could be used as suitable alternatives for cultural heritage purposes, as they have low toxicity and stability compared with synthetic pesticides. Even if most of the investigated solutions have already shown promising results, their efficiency, ecotoxicological, and chemical features are poorly investigated. In this manuscript, we aimed to evaluate the ecotoxicological profile of four fungal metabolites—namely, cavoxin, epi-epoformin, seiridin, and sphaeropsidone—with potential antimicrobial properties for monumental artworks. A battery of ecotoxicological tests using Aliivibrio fischeri (bacterium), Raphidocelis subcapitata (alga), Raphanus sativus L. (macrophyte), Daphnia magna (crustacean), and Caenorhabditis elegans (nematode) revealed a relative lower toxicity of these compounds, especially when compared with Preventol® and Rocima®, commercial biocides mainly used for the conservation of cultural heritage. [ABSTRACT FROM AUTHOR]

Ten Amaryllidaceae alkaloids (AAs) were isolated for the first time from Pancratium maritimum collected in Calabria region, Italy. They belong to different subgroups of this family and were identified as lycorine, which is the main alkaloid, 9-O-demethyllycorine, haemanthidine, haemanthamine, 11-hydroxyvittatine, homolycorine, pancracine, obliquine, tazettine and vittatine. Haemanthidine was isolated as a scalar mixture of two 6-epimers, as already known also for other 6-hydroxycrinine alkaloids, but for the first time they were separated as 6,11-O,O′-di-p-bromobenzoyl esters. The evaluation of the cytotoxic and antiviral potentials of all isolated compounds was undertaken. Lycorine and haemanthidine showed cytotoxic activity on Hacat cells and A431 and AGS cancer cells while, pancracine exhibited selective cytotoxicity against A431 cells. We uncovered that in addition to lycorine and haemanthidine, haemanthamine and pancracine also possess antiretroviral abilities, inhibiting pseudotyped human immunodeficiency virus (HIV)−1 with EC50 of 25.3 µM and 18.5 µM respectively. Strikingly, all the AAs isolated from P. maritimum were able to impede dengue virus (DENV) replication (EC50 ranged from 0.34–73.59 µM) at low to non-cytotoxic concentrations (CC50 ranged from 6.25 µM to >100 µM). Haemanthamine (EC50 = 337 nM), pancracine (EC50 = 357 nM) and haemanthidine (EC50 = 476 nM) were the most potent anti-DENV inhibitors. Thus, this study uncovered new antiviral properties of P. maritimum isolated alkaloids, a significant finding that could lead to the development of new therapeutic strategies to fight viral infectious diseases. [ABSTRACT FROM AUTHOR]

In this study, the computational analysis of electronic circular dichroism (ECD) spectra and the employment of biphenyl chiroptical probes were compared in the absolute configuration assignment of (-)-1α,2α,3β-trihydroxy-p-menthane (1), taken as a representative example of a UV-transparent chiral natural product. The usefulness of chiroptical probes in the configurational assignments of natural products and their complementarity to the computational protocols is herein highlighted. The biphenyl probe approach proves to be straightforward, reliable, and suitable for conformationally mobile and ECD silent compounds, not treatable by computational analysis of chiroptical data. [ABSTRACT FROM AUTHOR]

(+)-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 the 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. [ABSTRACT FROM AUTHOR]

NAD+-dependent histone deacetylases (sirtuins) are implicated in cellular processes such as proliferation, DNA repair, and apoptosis by regulating gene expression and the functions of numerous proteins. Due to their key role in cells, the discovery of small molecule sirtuin modulators has been of significant interest for diverse therapeutic applications. In particular, it has been shown that inhibition of sirtuin 1 and 2 activities is beneficial for cancer treatment. Here, we demonstrate that the fungal metabolite eurochevalierine from the fungus Neosartorya pseudofischeri inhibits sirtuin 1 and 2 activities (IC50 about 10 µM) without affecting sirtuin 3 activity. The binding modes of the eurochevalierine for sirtuin 1 and 2 have been identified through computational docking analyses. Accordingly, this sequiterpene alkaloid induces histone H4 and α-tubulin acetylation in various cancer cell models in which it induces strong cytostatic effects without affecting significantly the viability of healthy PBMCs. Importantly, eurochevalierine targets preferentially cancer cell proliferation (selectivity factor ≫ 7), as normal human primary CD34+ stem/progenitor cells were less affected by the treatment. Finally, eurochevalierine displays suitable drug-likeness parameters and therefore represent a promising scaffold for lead molecule optimization to study the mechanism and biological roles of sirtuins and potentially a basis for development into therapeutics. [ABSTRACT FROM AUTHOR]

The generation of natural product-like compound collections has become an important area of research due to low hit rates found with synthetic high-throughput libraries. One method of generating compounds occupying the areas of chemical space not accessible to synthetic planar heterocyclic structures is the utilization of natural products as starting materials. In the current work, using a ring-closing iodoalkoxylation reaction, alkaloid haemanthamine was transformed into a unique structural framework possessing an intricate ring system and a large number of stereocenters. The structure of the new compound was confirmed with an X-ray analysis. A small number of derivatives of this new compound were synthesized as a demonstration of the possibility of generating a large natural product-like compound collection based on the new structural framework. [ABSTRACT FROM AUTHOR]

Footnotes 1 B Disclaimer/Publisher's Note: b The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). Figure Graph: Figure 1 Structures of araufuranone (1), neovasinin (2), and 2,4-dihydroxy-6-hydroxymethylbenzaldehyde (3). Araufuranone: A New Phytotoxic Tetrasubstituted Dihydrofuro[3,2-b]furan-2(5H)-One Isolated from Ascochyta araujiae. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Neofusiccocum batangarum is the causal agent of scabby canker of cactus pear (Opuntia ficus-indica L.). The symptoms of this disease are characterized by crusty, perennial cankers, with a leathery, brown halo. Characteristically, a viscous polysaccharide exudate, caking on contact with air, leaks from cankers and forms strips or cerebriform masses on the surface of cactus pear cladodes. When this polysaccharide mass was partial purified, surprisingly, generated a gel. The TLC analysis and the HPLC profile of methyl 2-(polyhydroxyalkyl)-3-(o-tolylthiocarbomoyl)-thiazolidine-4R-carboxylates obtained from the mixture of monosaccharides produced by acid hydrolysis of the three EPSs examined in this research work [the polysaccharide component of the exudate (EPSC) and the EPSs extracted from asymptomatic (EPSH) and symptomatic (EPSD) cladodes] showed the presence of d-galactose, l-rhamnose, and d-glucose in a 1:1:0.5 ratio in EPSC while d-galactose, l-rhamnose, d-glucose, and d-xylose at the same ratio were observed in EPSH and EPSD. The presence of uronic acid residues in EPSC was also showed by solid state NMR and IR investigation. Furthermore, this manuscript reports the chemical-physical characterization of the gel produced by the infected cactus pear. [ABSTRACT FROM AUTHOR]

Grapevine (Vitis vinifera L.) can be affected by many different biotic agents, including tracheomycotic fungi such as Phaeomoniella chlamydospora and Phaeoacremonium minimum, which are the main causal agent of Esca and Petri diseases. Both fungi produce phytotoxic naphthalenone polyketides, namely scytalone and isosclerone, that are related to symptom development. The main objective of this study was to investigate the secondary metabolites produced by three Phaeoacremonium species and to assess their phytotoxicity by in vitro bioassay. To this aim, untargeted and targeted LC-MS/MS-based metabolomics were performed. High resolution mass spectrometer UHPLC-Orbitrap was used for the untargeted profiling and dereplication of secondary metabolites. A sensitive multi reaction monitoring (MRM) method for the absolute quantification of scytalone and isosclerone was developed on a UPLC-QTrap. Different isolates of P. italicum, P. alvesii and P. rubrigenum were grown in vitro and the culture filtrates and organic extracts were assayed for phytotoxicity. The toxic effects varied within and among fungal isolates. Isosclerone and scytalone were dereplicated by matching retention times and HRMS and MS/MS data with pure standards. The amount of scytalone and isosclerone differed within and among fungal species. To our best knowledge, this is the first study that applies an approach of LC-MS/MS-based metabolomics to investigate differences in the metabolic composition of organic extracts of Phaeoacremonium species culture filtrates. [ABSTRACT FROM AUTHOR]

Up to 60 species of fungi in the Botryosphaeriaceae family, genera Cadophora, Cryptovalsa, Cylindrocarpon, Diatrype, Diatrypella, Eutypa, Eutypella, Fomitiporella, Fomitiporia, Inocutis, Phaeoacremonium and Phaeomoniella have been isolated from decline-affected grapevines all around the World. The main grapevine trunk diseases of mature vines are Eutypa dieback, the esca complex and cankers caused by the Botryospheriaceae, while in young vines the main diseases are Petri and black foot diseases. To understand the mechanism of these decline-associated diseases and the symptoms associated with them, the toxins produced by the pathogens involved in these diseases were isolated and characterised chemically and biologically. So far the toxins of only a small number of these decline fungi have been studied. This paper presents an overview of the toxins produced by the most serious of these vine wood pathogens: Eutypa lata, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and some taxa in the Botryosphaeriaceae family, and examines how these toxins produce decline symptoms. The chemical structure of these metabolites and in some cases their vivotoxin nature are also discussed. [ABSTRACT FROM AUTHOR]

Natural products are a vital source for agriculture, medicine, cosmetic and other fields. Among them alkylamides are a broad and expanding group found in at least 33 plant families. Frequently, they possess a simple carbon skeleton architecture but show broad structural variability and important properties such as immunomodulatory, antimicrobial, antiviral, larvicidal, insecticidal and antioxidant properties, amongst others. Despite to these several and promising biological activities, up to today, only two reviews have been published on natural alkylamides. One focuses on their potential pharmacology application and their distribution in the plant kingdom and the other one on the bioactive alkylamides specifically found in Annona spp. The present review is focused on the plant bioactive cinnamoyltyramine alkylamides, which are subject of several works reported in the literature. Furthermore, the co-metabolites isolated from the same natural sources and their biological activities are also reported. [ABSTRACT FROM AUTHOR]

9-Hydroxynerolidol, 9-oxonerolidol, and chiliadenol B are three farnesane-type sesquiterpenoids isolated from Chiliadenus lopadusanus that have shown an interesting activity against human pathogens as Gram+ and Gram− bacteria resistant to antibiotics. However, the absolute configuration (AC) of these interesting sesquiterpenes has not been assigned so far. Vibrational and electronic circular dichroism spectra have been recorded and correlations are pointed out for the three compounds. Density functional theory (DFT) calculations are used in conjunction with Mosher's method of investigation to assign AC. Statistical analysis is considered to quantitatively define the choice of AC from VCD spectra. [ABSTRACT FROM AUTHOR]

Pseudomonas fluorescens 9 and Bacillus subtilis 54, proposed as biofungicides to control Macrophomina phaseolina, a dangerous pathogen of soybean and other crops, were grown in vitro to evaluate their ability to produce metabolites with antifungal activity. The aim of the manuscript was to identify the natural compounds responsible for their antifungal activity. Only the culture filtrates of P. fluorescens 9 showed strong antifungal activity against M. phaseolina. Its organic extract contained phenazine and mesaconic acid (1 and 2), whose antifungal activity was tested against M. phaseolina, as well as Cercospora nicotianae and Colletotrichum truncatum, other pathogens of soybean; however, only compound 1 exhibited activity. The antifungal activity of compound 1 was compared to phenazine-1-carboxylic acid (PCA, 3), 2-hydroxyphenazine (2-OH P, 4), and various semisynthetic phenazine nitro derivatives in order to perform a structure–activity relationship (SAR) study. PCA and phenazine exhibited the same percentage of growth inhibition in M. phaseolina and C. truncatum, whereas PCA (3) showed lower activity against C. nicotianae than phenazine. 2-Hydroxyphenazine (4) showed no antifungal activity against M. phaseolina. The results of the SAR study showed that electron attractor (COOH and NO2) or repulsor (OH) groups significantly affect the antifungal growth, as well as their α- or β-location on the phenazine ring. Both PCA and phenazine could be proposed as biopesticides to control the soybean pathogens M. phaseolina, C. nicotianae, and C. truncatum, and these results should prompt an investigation of their large-scale production and their suitable formulation for greenhouse and field applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The use of natural products in agriculture as pesticides has been strongly advocated. However, it is necessary to assess their toxicity to ensure their safe use. In the present study, mammalian cell lines and fish models of the zebrafish (Danio rerio) and medaka (Oryzias latipes) have been used to investigate the toxic effects of ten natural products which have potential applications as biopesticides. The fungal metabolites cavoxin, epi-epoformin, papyracillic acid, seiridin and sphaeropsidone, together with the plant compounds inuloxins A and C and ungeremine, showed no toxic effects in mammalian cells and zebrafish embryos. Conversely, cyclopaldic and α-costic acids, produced by Seiridium cupressi and Dittrichia viscosa, respectively, caused significant mortality in zebrafish and medaka embryos as a result of yolk coagulation. However, both compounds showed little effect in zebrafish or mammalian cell lines in culture, thus highlighting the importance of the fish embryotoxicity test in the assessment of environmental impact. Given the embryotoxicity of α-costic acid and cyclopaldic acid, their use as biopesticides is not recommended. Further ecotoxicological studies are needed to evaluate the potential applications of the other compounds. [ABSTRACT FROM AUTHOR]

In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway. [ABSTRACT FROM AUTHOR]

Fusicoccin is the α glucoside of a carbotricyclic diterpene, produced by the fungus Phomopsis amygdali (previously classified as Fusicoccum amygdali), the causal agent of almond and peach canker disease. A great interest in this molecule started when it was discovered that it brought about an irreversible stomata opening of higher plants, thereby inducing the wilting of their leaves. Since then, several studies were carried out to elucidate its biological activity, biosynthesis, structure, structure-activity relationships and mode of action. After sixty years of research and more than 1800 published articles, FC is still the most studied phytotoxin and one of the few whose mechanism of action has been elucidated in detail. The ability of FC to stimulate several fundamental plant processes depends on its ability to activate the plasma membrane H+-ATPase, induced by eliciting the association of 14-3-3 proteins, a class of regulatory molecules widespread in eukaryotes. This discovery renewed interest in FC and prompted more recent studies aimed to ascertain the ability of the toxin to influence the interaction between 14-3-3 proteins and their numerous client proteins in animals, involved in the regulation of basic cellular processes and in the etiology of different diseases, including cancer. This review covers the different aspects of FC research partially treated in different previous reviews, starting from its discovery in 1964, with the aim to outline the extraordinary pathway which led this very uncommon diterpenoid to evolve from a phytotoxin into a tool in plant physiology and eventually into a 14-3-3-targeted drug. [ABSTRACT FROM AUTHOR]

Crinum biflorum Rottb. (syn. Crinum distichum) is an Amaryllidaceae plant used in African traditional medicine but very few studies have been performed on this species from a chemical and applicative point of view. Bulbs of C. biflorum, collected in Senegal, were extracted with ethanol by Soxhlet and the corresponding organic extract was purified using chromatographic methods. The pure compounds were chemically characterized by spectroscopic techniques (1D and 2D 1H and 13C NMR, HR MS and ECD) and X-ray analysis. Four homoisoflavonoids (1–4) and one alkylamide (5) were isolated and characterized as 5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (1), as 3-hydroxy-5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (2), as 3-hydroxy-5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (3) and as 5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (4), and the alkylamide as (E)-N-(4-hydroxyphenethyl)-3-(4-hydroxyphenyl)acrylamide (5), commonly named N-p-coumaroyltyramine. The relative configuration of compound 1 was verified thanks to the X-ray analysis which also allowed us to confirm its racemic nature. The absolute configurations of compounds 2 and 3 were assigned by comparing their ECD spectra with those previously reported for urgineanins A and B. Flavanoids 1, 3 and 4 showed promising anticancer properties being cytotoxic at low micromolar concentrations towards HeLa and A431 human cancer cell lines. The N-p-coumaroyltyramine (5) was selectively toxic to A431 and HeLa cancer cells while it protected immortalized HaCaT cells against oxidative stress induced by hydrogen peroxide. Compounds 1–4 also inhibited acetylcholinesterase activity with compound 3 being the most potent. The anti-amylase and the strong anti-glucosidase activity of compound 5 were confirmed. Our results show that C. biflorum produces compounds of therapeutic interest with anti-diabetic, anti-tumoral and anti-acetylcholinesterase properties. [ABSTRACT FROM AUTHOR]

Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract obtained from its aerial parts demonstrated antibiotic activity against Enterococcus faecalis and was fractionated by bioguided purification procedures affording five main sesquiterpene lactones. They were identified by spectroscopic methods (NMR and ESIMS data) as guaiantrienolides, i.e., 6-acetoxy-1β-,6-acetoxy-1α-, and 6-acetoxy-10-β-hydroxyguaiantrienolide (1–3), and germacrenolides, i.e., haagenolide and 1,10-epoxyhaagenolide (4 and 5). The absolute configuration was assigned by applying the advanced Mosher's method to haagenolide and by X-ray diffraction analysis to 1,10-epoxyhaagenolide. The specific antibiotic and antibiofilm activities were tested toward the clinical isolates of Enterococcus faecalis. The results showed that compounds 3–5 have antibacterial activity against all the strains of E. faecalis, while compound 2 exhibited activity only toward some strains. Compound 1 did not show this activity but had only antibiofilm properties. Thus, these metabolites have potential as new antibiotics and antibiofilm against drug resistant opportunistic pathogens. [ABSTRACT FROM AUTHOR]

Dietary supplements based on Teucrium chamaedrys L. subsp. chamaedrys aerial parts were banned, due to the hepatotoxicity of furan-containing neo-clerodane constituents. Indeed, the plant leaf content in phenolic compounds could be further exploited for their antioxidant capability. Accordingly, bio-guided fractionation strategies have been applied, obtaining seven partially purified extracts. These latter were chemically investigated through 1D and 2D NMR techniques and tested for their antiradical, reducing and cytotoxic capability. Data acquired highlighted that, through a simple phytochemical approach, a progressive neo-clerodane depletion occurred, while maximizing phenylethanoid glycosides in alcoholic fractions. Thus, although the plant cannot be used as a botanical remedy as such, it is suggested as a source of healthy compounds, pure or in mixture, to be handled in pharmaceutical, nutraceutical and/or cosmeceutical sectors. [ABSTRACT FROM AUTHOR]

A protocol based on the combination of different analytical methodologies is proposed to standardize the experimental conditions for reproducible formulations of hybrid hydrogels. The final hybrid material, based on the combination of gelatin and chitosan functionalized with methylfuran and cross-linked with 4-arm-PEG-maleimide, is able to mimic role, dynamism, and structural complexity of the extracellular matrix. Physical–chemical properties of starting polymers and finals constructs were characterized exploiting the combination of HP-SEC-TDA, UV, FT-IR, NMR, and TGA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The holoparasitic broomrape weeds (Orobanche and Phelipanche species) cause severe yield losses throughout North Africa, the Middle East, and Southern and Eastern Europe. These parasitic weeds form an haustorium at the tip of their radicles to infect the crop upon detection of the host-derived haustorium-inducing factors. Until now, the haustorial induction in the broomrapes remains less studied than in other parasitic plant species. Known haustorium-inducing factors active in hemiparasites, such as Striga and Triphysaria species, were reported to be inefficient for the induction of haustoria in broomrape radicles. In this work, the haustorium-inducing activity of p-benzoquinone and 2,6-dimethoxy-p-benzoquinone (BQ and DMBQ) on radicles of three different broomrapes, namely Orobanche cumana, Orobanche minor and Phelipanche ramosa, is reported. Additional allelopathic effects of benzoquinones on radicle growth and radicle necrosis were studied. The results of this work suggest that benzoquinones play a role in the induction of haustorium in broomrapes. Although dependent on the broomrape species assayed and the concentration of quinones used in the test, the activity of BQ appeared to be stronger than that of DMBQ. The redox property represented by p-benzoquinone, which operates in several physiological processes of plants, insects and animals, is invoked to explain this different activity. This work confirms the usefulness of benzoquinones as haustorium-inducing factors for holoparasitic plant research. The findings of this work could facilitate future studies in the infection process, such as host-plant recognition and haustorial formation. [ABSTRACT FROM AUTHOR]

Aedes albopictus (Skuse) is a widespread mosquito, a vector of important human arboviruses, including Chikungunya, Dengue and Zika. It is an extremely difficult species to control even for the onset of resistances to chemicals insecticides, therefore ecofriendly products are urgently needed. In this study, the activity of Amaryllidaceae alkaloids and some of their semisynthetic derivatives, of 2-methoxy-1,4-naphthoquinone and two analogues, of cyclopaldic acid and epi-epoformin on the survival and development of Ae. albopictus larvae was evaluated. First-instar larval exposure for 24 and 48 h to cyclopaldic acid, resulted in mortality mean per-centage of 82.4 and 96.9 respectively; 1,2-O,O-diacetyllycorine 48h post-treatment caused 84.7% mortality. Larval and pupal duration were proved to decrease significantly when larvae were exposed to cyclopaldic acid, 1,2-O,O-diacetyllycorine and N-methyllycorine iodide. The mean number of third-instar larvae surviving to 2-methyl-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone was significantly lower than the number of correspondent control larvae over the time. This study indicated that 1,2-O,O'-diacetyllycorine, N-methyllycorine iodide, cyclopaldic acid and 1,4-naphthoquinone structural derivatives have good potential for developing bioinsecticides for mosquito control programs. The obtained results are of general interest due to the global importance of the seri-ous human diseases such a vector is able to spread. [ABSTRACT FROM AUTHOR]

In recent decades, intensive crop management has involved excessive use of pesticides or fertilizers, compromising environmental integrity and public health. Accordingly, there has been worldwide pressure to find an eco-friendly and safe strategy to ensure agricultural productivity. Among alternative approaches, Plant Growth-Promoting (PGP) rhizobacteria are receiving increasing attention as suitable biocontrol agents against agricultural pests. In the present study, 22 spore-forming bacteria were selected among a salt-pan rhizobacteria collection for their PGP traits and their antagonistic activity against the plant pathogen fungus Macrophomina phaseolina. Based on the higher antifungal activity, strain RHFS10, identified as Bacillus vallismortis, was further examined and cell-free supernatant assays, column purification, and tandem mass spectrometry were employed to purify and preliminarily identify the antifungal metabolites. Interestingly, the minimum inhibitory concentration assessed for the fractions active against M. phaseolina was 10 times lower and more stable than the one estimated for the commercial fungicide pentachloronitrobenzene. These results suggest the use of B. vallismortis strain RHFS10 as a potential plant growth-promoting rhizobacteria as an alternative to chemical pesticides to efficiently control the phytopathogenic fungus M. phaseolina. [ABSTRACT FROM AUTHOR]

Allelopathic potential of buckwheat roots on the radicle growth of the broomrape weed species Orobanche cumana and Phelipanche ramosa was studied. Buckwheat root exudates induced a significant growth inhibition in P. ramosa radicles but radicles of O. cumana were not affected. Among the metabolites present in the root organic extract we identified the flavonol quercetin and the stilbene p-coumaric acid methyl ester with only quercetin showing inhibitory effect on P. ramosa. The activity of quercetin was compared with other two similar flavanoids, the flavone apigenin and the dihydroflavanol 3-O-acetylpadmatin extracted respectively from Lavandula stoechas and Dittrichia viscosa plants. In this comparative assay only 3-O-acetylpadmatin besides quercetin, showed inhibition activity of radicle growth while apigenin was inactive. These results indicated that the presence of two ortho-free hydroxy groups of C ring, like catechol, could be an important feature to impart activity while the carbon skeleton of B ring and substituents of both A and B rings are not essential. Besides reduction of radicle growth, haustorium induction was observed at the tip of P. ramosa radicles treated with quercetin which swelled and a layer of papillae was formed. Activity of quercetin on haustorium induction in P. ramosa was assayed in comparison with the known haustorium-inducing factor 2,6-dimethoxy-p-benzoquinone (DMBQ) and a three partial methyl ether derivatives semisynthetized from quercetin. Results indicated that P. ramosa haustorium was induced by DMBQ at concentrations of 1–0.5 mM and quercetin and its derivatives at concentration range 0.1–0.05 mM. [ABSTRACT FROM AUTHOR]

Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases. [ABSTRACT FROM AUTHOR]

In this paper, the first phytochemical analysis of the ethanolic extract of Daphne sericea Vahl flowering aerial parts collected in Italy and its biological activities were reported. Eleven compounds were identified i.e., α-linolenic acid (1), tri-linoleoyl-sn-glycerol (2), pheophorbide a ethyl ester (3), pilloin (4), sinensetin (5), yuanhuanin (6), rutamontine (7), syringin (8), p-coumaric acid (9), p-anisic acid (10) and caffeic acid (11). To the best of our knowledge, compounds (1-4, 7-8 and 10) were isolated from D. sericea for the first time during this work, whereas sinensetin (5) represents a newly identified component of the entire Thymelaeaceae family. The extract was found to possess radical scavenging against both DPPH• and 2,2′-azino-bis(3-thylbenzothiazoline-6-sulfonic acid (ABTS•+) radicals, with at least a 40-fold higher potency against the latter. Moreover, chelating abilities against both ferrous and ferric ions have been highlighted, thus suggesting a possible indirect antioxidant power of the extract. Although the precise bioactive compounds remain to be discovered, the polyphenolic constituents, including phenolic acids, tannins and flavonoids, seem to contribute to the antioxidant power of the phytocomplex. In addition, the extract produced cytotoxic effects in MDA-MB-231 and U87-MG cancer cell lines, especially at the concentration of 625 μg/mL and after 48–72 h. Further studies are required to clarify the contribution of the identified compounds in the bioactivities of the extract and to support possible future applications. [ABSTRACT FROM AUTHOR]

Chiliadenus lopadusanus Brullo is an Asteraceae plant species endemic to Lampedusa island, the largest island of the Pelage archipelago, Italy. The organic extract of its whole aerial parts, showing antibiotic activity against Staphylococcus aureus and Acinetobacter baumannii, wasfractionated employing bioguided purification procedures affording three main farnesane-type sesquiterpenoids. They were identified by spectroscopic methods (NMR and ESIMS data) as the (E)-3,7,11-trimethyldodeca-1,6,10-triene-3,9-diol, (E)-10-hydroxy-2,6,10-trimethyldodeca-2,6,11- trien-4-one and (E)-10-hydroxy-2,6,10-trimethyl-dodeca-6,11-dien-4-one, commonly named 9-hydroxynerolidol, 9-oxonerolidol, and chiliadenol B, respectively. These three sesquiterpenes, isolated for the first time from C. lopadusanus, were tested on methicillin-resistant S. aureus and A. baumannii showing antibacterial and antibiofilm activities. This plant could be used as a source to isolate secondary metabolites as potential new antibiotics. [ABSTRACT FROM AUTHOR]

Fungi are among the biotic agents that can cause deterioration of building stones and cultural heritage. The most common methods used to control fungal spread and growth are based on chemical pesticides. However, the massive use of these synthetic chemicals produces heavy environmental pollution and risk to human and animal health. Furthermore, their use is time dependent and relies on the repetition of treatments, which increases the possibility of altering building stones and culture heritage through environmental contamination. One alternative is the use of natural products with high antifungal activity, which can result in reduced toxicity and deterioration of archeological remains. Recently, three fungal strains, namely Aspergillus niger, Alternaria alternata and Fusarium oxysporum, were isolated as damaging agents from the external tuff wall of the Roman remains "Villa of Poppea" in Oplontis, Naples, Italy. In this manuscript, three selected fungal metabolites, namely cyclopaldic acid, cavoxin and epi-epoformin, produced by fungi pathogenic for forest plants, were evaluated as potential antifungal compounds against the above fungi. Cavoxin and epi-epoformin showed antifungal activity against Asperigillus niger and Fusarium oxysporum, while cyclopaldic acid showed no activity when tested on the three fungi. The same antifungal activity was observed in vitro experiments on infected stones of the Neapolitan yellow tuff (NYT), a volcanic lithotype widely diffused in the archeological sites of Campania, Italy. This study represents a first step in the use of these two fungal metabolites to allow better preservation of artworks and to guarantee the conditions suitable for their conservation. [ABSTRACT FROM AUTHOR]

Drechslera gigantea Heald & Wolf is a worldwide-spread necrotrophic fungus closely related to the Bipolaris genus, well-known because many member species provoke severe diseases in cereal crops and studied because they produce sesterpenoid phytoxins named ophiobolins which possess interesting biological properties. The unfolded protein response (UPR) is a conserved mechanism protecting eukaryotic cells from the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER). In plants, consolidated evidence supports the role of UPR in the tolerance to abiotic stress, whereas much less information is available concerning the induction of ER stress by pathogen infection and consequent UPR elicitation as part of the defense response. In this study, the infection process of D. gigantea in Arabidopsis thaliana wild type and UPR-defective bzip28 bzip60 double mutant plants was comparatively investigated, with the aim to address the role of UPR in the expression of resistance to the fungal pathogen. The results of confocal microscopy, as well as of qRT-PCR transcript level analysis of UPR genes, proteomics, microRNAs expression profile and HPLC-based hormone analyses demonstrated that ophiobolin produced by the fungus during infection compromised ER integrity and that impairment of the IRE1/bZIP60 pathway of UPR hampered the full expression of resistance, thereby enhancing plant susceptibility to the pathogen. [ABSTRACT FROM AUTHOR]

Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and flavonoids content. Hundreds of alkaloids have been isolated until now and several scientific publications reported their sources, chemical structures, and biological activities. During the last decade, some unstudied Amaryllidaceae plants were the object of in-depth investigations to isolate and chemically and biologically characterize new and already known alkaloids as well as some analogues. This review describes the isolation and chemical and biological characterization of the Amaryllidaceae alkaloids, and their analogues obtained in the last decade, focusing the discussion on the new ones. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties. [ABSTRACT FROM AUTHOR]