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Glioblastoma (GBM) is the most aggressive form of glioma tumor in adult brain. Among the numerous factors responsible for GBM cell proliferation and invasion, neurotransmitters such as dopamine, serotonin and glutamate can play key roles. Studies performed in mice housed in germ-free (GF) conditions demonstrated the relevance of the gut-brain axis in a number of physiological and pathological conditions. The gut–brain communication is made possible by vagal/nervous and blood/lymphatic routes and pave the way for reciprocal modulation of functions. The gut microbiota produces and consumes a wide range of molecules, including neurotransmitters (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid [GABA], and glutamate) that reach their cellular targets through the bloodstream. Growing evidence in animals suggests that modulation of these neurotransmitters by the microbiota impacts host neurophysiology and behavior, and affects neural cell progenitors and glial cells, along with having effects on tumor cell growth. In this review we propose a new perspective connecting neurotransmitter modulation by gut microbiota to glioma progression.
Giuseppina D’Alessandro; Clotilde Lauro; Deborah Quaglio; Francesca Ghirga; Bruno Botta; Flavia Trettel; Cristina Limatola. Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma. Cancers 2021, 13, 2810 .
AMA StyleGiuseppina D’Alessandro, Clotilde Lauro, Deborah Quaglio, Francesca Ghirga, Bruno Botta, Flavia Trettel, Cristina Limatola. Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma. Cancers. 2021; 13 (11):2810.
Chicago/Turabian StyleGiuseppina D’Alessandro; Clotilde Lauro; Deborah Quaglio; Francesca Ghirga; Bruno Botta; Flavia Trettel; Cristina Limatola. 2021. "Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma." Cancers 13, no. 11: 2810.
The chemical profile of the female inflorescence extracts from seven Cannabis sativa L. dioecious cultivars (Carmagnola, Fibranova, Eletta Campana, Antal, Tiborszallasi, Kompolti, and Tisza) was monitored at three harvesting stages (4, 14, and 30 September), reaching from the beginning of flowering to end of flowering/beginning of seed formation, using untargeted nuclear magnetic resonance (NMR) and targeted (ultra-high-performance liquid chromatography (UHPLC) and spectrophotometry) analyses. The tetrahydrocannabinol content was always below the legal limits (<0.6%) in all the analyzed samples. The NMR metabolite profile (sugars, organic acids, amino acids, and minor compounds) subjected to principal components analysis (PCA) showed a strong variability according to the harvesting stages: samples harvested in stage I were characterized by a high content of sucrose and myo-inositol, whereas the ones harvested in stage II showed high levels of succinic acid, alanine, valine, isoleucine, phenylalanine, and threonine. Samples harvested in stage III were characterized by high levels of glucose, fructose, choline, trigonelline, malic acid, formic acid, and some amino acids. The ratio between chlorophylls and carotenoids content indicated that all plants grew up exposed to the sun, the Eletta Campana cultivar having the highest pigment amount. Tiborszallasi cultivar showed the highest polyphenol content. The highest antioxidant activity was generally observed in stage II. All these results suggested that the Cannabis sativa L. inflorescences of each analyzed dioecious hemp cultivar presented a peculiar chemical profile affected by the harvesting stage. This information could be useful for producers and industries to harvest inflorescences in the appropriate stage to obtain samples with a peculiar chemical profile suitable for proper applications.
Mattia Spano; Giacomo Di Matteo; Cinzia Ingallina; Bruno Botta; Deborah Quaglio; Francesca Ghirga; Silvia Balducci; Silvia Cammarone; Enio Campiglia; Anna Giusti; Giuliana Vinci; Mattia Rapa; Salvatore Ciano; Luisa Mannina; Anatoly Sobolev. A Multimethodological Characterization of Cannabis sativa L. Inflorescences from Seven Dioecious Cultivars Grown in Italy: The Effect of Different Harvesting Stages. Molecules 2021, 26, 2912 .
AMA StyleMattia Spano, Giacomo Di Matteo, Cinzia Ingallina, Bruno Botta, Deborah Quaglio, Francesca Ghirga, Silvia Balducci, Silvia Cammarone, Enio Campiglia, Anna Giusti, Giuliana Vinci, Mattia Rapa, Salvatore Ciano, Luisa Mannina, Anatoly Sobolev. A Multimethodological Characterization of Cannabis sativa L. Inflorescences from Seven Dioecious Cultivars Grown in Italy: The Effect of Different Harvesting Stages. Molecules. 2021; 26 (10):2912.
Chicago/Turabian StyleMattia Spano; Giacomo Di Matteo; Cinzia Ingallina; Bruno Botta; Deborah Quaglio; Francesca Ghirga; Silvia Balducci; Silvia Cammarone; Enio Campiglia; Anna Giusti; Giuliana Vinci; Mattia Rapa; Salvatore Ciano; Luisa Mannina; Anatoly Sobolev. 2021. "A Multimethodological Characterization of Cannabis sativa L. Inflorescences from Seven Dioecious Cultivars Grown in Italy: The Effect of Different Harvesting Stages." Molecules 26, no. 10: 2912.
Gene expression regulation by small interfering RNA (siRNA) holds promise in treating a wide range of diseases through selective gene silencing. However, successful clinical application of nucleic acid-based therapy requires novel delivery options. Herein, to achieve efficient delivery of negatively charged siRNA duplexes, the internal cavity of “humanized” chimeric Archaeal ferritin (HumAfFt) was specifically decorated with novel cationic piperazine-based compounds (PAs). By coupling these rigid-rod-like amines with thiol-reactive reagents, chemoselective conjugation was efficiently afforded on topologically selected cysteine residues properly located inside HumAfFt. The capability of PAs-HumAfFt to host and deliver siRNA molecules through human transferrin receptor (TfR1), overexpressed in many cancer cells, was explored. These systems allowed siRNA delivery into HeLa, HepG2, and MCF-7 cancer cells with improved silencing effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression with respect to traditional transfection methodologies and provided a promising TfR1-targeting system for multifunctional siRNA delivery to therapeutic applications.
Natalia Pediconi; Francesca Ghirga; Cristina Del Plato; Giovanna Peruzzi; Constantinos M. Athanassopoulos; Mattia Mori; Maria Elisa Crestoni; Davide Corinti; Franco Ugozzoli; Chiara Massera; Alessandro Arcovito; Bruno Botta; Alberto Boffi; Deborah Quaglio; Paola Baiocco. Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells. Bioconjugate Chemistry 2021, 32, 1105 -1116.
AMA StyleNatalia Pediconi, Francesca Ghirga, Cristina Del Plato, Giovanna Peruzzi, Constantinos M. Athanassopoulos, Mattia Mori, Maria Elisa Crestoni, Davide Corinti, Franco Ugozzoli, Chiara Massera, Alessandro Arcovito, Bruno Botta, Alberto Boffi, Deborah Quaglio, Paola Baiocco. Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells. Bioconjugate Chemistry. 2021; 32 (6):1105-1116.
Chicago/Turabian StyleNatalia Pediconi; Francesca Ghirga; Cristina Del Plato; Giovanna Peruzzi; Constantinos M. Athanassopoulos; Mattia Mori; Maria Elisa Crestoni; Davide Corinti; Franco Ugozzoli; Chiara Massera; Alessandro Arcovito; Bruno Botta; Alberto Boffi; Deborah Quaglio; Paola Baiocco. 2021. "Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells." Bioconjugate Chemistry 32, no. 6: 1105-1116.
We review the successful application of computer-aided methods to screen a unique and high-diversity in house collection library composed of around 1000 individual natural products.
Francesca Ghirga; Deborah Quaglio; Mattia Mori; Silvia Cammarone; Antonia Iazzetti; Antonella Goggiamani; Cinzia Ingallina; Bruno Botta; Andrea Calcaterra. A unique high-diversity natural product collection as a reservoir of new therapeutic leads. Organic Chemistry Frontiers 2020, 8, 996 -1025.
AMA StyleFrancesca Ghirga, Deborah Quaglio, Mattia Mori, Silvia Cammarone, Antonia Iazzetti, Antonella Goggiamani, Cinzia Ingallina, Bruno Botta, Andrea Calcaterra. A unique high-diversity natural product collection as a reservoir of new therapeutic leads. Organic Chemistry Frontiers. 2020; 8 (5):996-1025.
Chicago/Turabian StyleFrancesca Ghirga; Deborah Quaglio; Mattia Mori; Silvia Cammarone; Antonia Iazzetti; Antonella Goggiamani; Cinzia Ingallina; Bruno Botta; Andrea Calcaterra. 2020. "A unique high-diversity natural product collection as a reservoir of new therapeutic leads." Organic Chemistry Frontiers 8, no. 5: 996-1025.
Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.
Bruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules 2020, 25, 3619 .
AMA StyleBruno Casciaro, Laura Mangiardi, Floriana Cappiello, Isabella Romeo, Maria Rosa Loffredo, Antonia Iazzetti, Andrea Calcaterra, Antonella Goggiamani, Francesca Ghirga, Maria Luisa Mangoni, Bruno Botta, Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules. 2020; 25 (16):3619.
Chicago/Turabian StyleBruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. 2020. "Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections." Molecules 25, no. 16: 3619.
With the aim to identify novel inhibitors of parasitic nematode thymidylate synthase (TS), we screened in silico an in-house library of natural compounds, taking advantage of a model of nematode TS three-dimensional (3D) structure and choosing candidate compounds potentially capable of enzyme binding/inhibition. Selected compounds were tested as (i) inhibitors of the reaction catalyzed by TSs of different species, (ii) agents toxic to a nematode parasite model (C. elegans grown in vitro), (iii) inhibitors of normal human cell growth, and (iv) antitumor agents affecting human tumor cells grown in vitro. The results pointed to alvaxanthone as a relatively strong TS inhibitor that causes C. elegans population growth reduction with nematocidal potency similar to the anthelmintic drug mebendazole. Alvaxanthone also demonstrated an antiproliferative effect in tumor cells, associated with a selective toxicity against mitochondria observed in cancer cells compared to normal cells.
Piotr Maj; Mattia Mori; Justyna Sobich; Joanna Markowicz; Łukasz Uram; Zbigniew Zieliński; Deborah Quaglio; Andrea Calcaterra; Ylenia Cau; Bruno Botta; Wojciech Rode. Alvaxanthone, a Thymidylate Synthase Inhibitor with Nematocidal and Tumoricidal Activities. Molecules 2020, 25, 2894 .
AMA StylePiotr Maj, Mattia Mori, Justyna Sobich, Joanna Markowicz, Łukasz Uram, Zbigniew Zieliński, Deborah Quaglio, Andrea Calcaterra, Ylenia Cau, Bruno Botta, Wojciech Rode. Alvaxanthone, a Thymidylate Synthase Inhibitor with Nematocidal and Tumoricidal Activities. Molecules. 2020; 25 (12):2894.
Chicago/Turabian StylePiotr Maj; Mattia Mori; Justyna Sobich; Joanna Markowicz; Łukasz Uram; Zbigniew Zieliński; Deborah Quaglio; Andrea Calcaterra; Ylenia Cau; Bruno Botta; Wojciech Rode. 2020. "Alvaxanthone, a Thymidylate Synthase Inhibitor with Nematocidal and Tumoricidal Activities." Molecules 25, no. 12: 2894.
The discovery of antibiotics has revolutionized the medicine and treatment of microbial infections. However, the current scenario has highlighted the difficulties in marketing new antibiotics and an exponential increase in the appearance of resistant strains. On the other hand, research in the field of drug-discovery has revaluated the potential of natural products as a unique source for new biologically active molecules and scaffolds for the medicinal chemistry. In this review, we first contextualized the worldwide problem of antibiotic resistance and the importance that natural products of plant origin acquire as a source of new lead compounds. We then focused on terpenes and their potential development as antimicrobials, highlighting those studies that showed an activity against conventional antibiotic-resistant strains.
Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics 2020, 9, 1 .
AMA StyleFloriana Cappiello, Maria Rosa Loffredo, Cristina Del Plato, Silvia Cammarone, Bruno Casciaro, Deborah Quaglio, Maria Luisa Mangoni, Bruno Botta, Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics. 2020; 9 (6):1.
Chicago/Turabian StyleFloriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. 2020. "The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections." Antibiotics 9, no. 6: 1.
Cationic antimicrobial peptides (AMPs) are an interesting class of gene-encoded molecules endowed with a broad-spectrum of anti-infective activity and immunomodulatory properties. They represent promising candidates for the development of new antibiotics, mainly due to their membraneperturbing mechanism of action that very rarely induces microbial resistance. However, bringing AMPs into the clinical field is hampered by some intrinsic limitations, encompassing low peptide bioavailability at the target site and high peptide susceptibility to proteolytic degradation. In this regard, nanotechnologies represent an innovative strategy to circumvent these issues. According to the literature, a large variety of nanoparticulate systems have been employed for drug-delivery, bioimaging, biosensors or nanoantibiotics. The possibility of conjugating different types of molecules, including AMPs, to these systems, allows the production of nanoformulations able to enhance the biological profile of the compound while reducing its cytotoxicity and prolonging its residence time. In this minireview, inorganic gold nanoparticles (NPs) and biodegradable polymeric NPs made of poly(lactide-coglycolide) are described with particular emphasis on examples of the conjugation of AMPs to them, to highlight the great potential of such nanoformulations as alternative antimicrobials.
Bruno Casciaro; Francesca Ghirga; Deborah Quaglio; Maria Luisa Mangoni. Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides. Current Protein & Peptide Science 2020, 21, 429 -438.
AMA StyleBruno Casciaro, Francesca Ghirga, Deborah Quaglio, Maria Luisa Mangoni. Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides. Current Protein & Peptide Science. 2020; 21 (4):429-438.
Chicago/Turabian StyleBruno Casciaro; Francesca Ghirga; Deborah Quaglio; Maria Luisa Mangoni. 2020. "Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides." Current Protein & Peptide Science 21, no. 4: 429-438.
The chemical composition of the inflorescences from four Cannabis sativa L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines). All cultivars in each harvesting period showed a THC content below the Italian legal limit, although in general THC content increased over the season. Citric acid, malic acid and glucose showed the highest content in the late flowering period, whereas the content of proline drastically decreased after June in all cultivars. Neophytadiene, nerolidol and chlorogenic acid were quantified only in Felina 32 cultivar, characterized also by a very high content of flavonoids, whereas alloaromadendrene and trans-cinnamic acid were detected only in Uso-31 cultivar. Naringenin and naringin were present only in Fedora 17 and Ferimon cultivars, respectively. Moreover, Ferimon had the highest concentration of biogenic amines, especially in July and August. Cadaverine was present in all cultivars but only in September. These results suggest that the chemical composition of Cannabis sativa L. inflorescences depends on the cultivar and on the harvesting period. Producers can use this information as a guide to obtain inflorescences with peculiar chemical characteristics according to the specific use.
Cinzia Ingallina; Anatoly P. Sobolev; Simone Circi; Mattia Spano; Caterina Fraschetti; Antonello Filippi; Antonella Di Sotto; Silvia Di Giacomo; Giulia Mazzoccanti; Francesco Gasparrini; Deborah Quaglio; Enio Campiglia; Simone Carradori; Marcello Locatelli; Giuliana Vinci; Mattia Rapa; Salvatore Ciano; Anna Maria Giusti; Bruno Botta; Francesca Ghirga; Donatella Capitani; Luisa Mannina. Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening. Molecules 2020, 25, 1908 .
AMA StyleCinzia Ingallina, Anatoly P. Sobolev, Simone Circi, Mattia Spano, Caterina Fraschetti, Antonello Filippi, Antonella Di Sotto, Silvia Di Giacomo, Giulia Mazzoccanti, Francesco Gasparrini, Deborah Quaglio, Enio Campiglia, Simone Carradori, Marcello Locatelli, Giuliana Vinci, Mattia Rapa, Salvatore Ciano, Anna Maria Giusti, Bruno Botta, Francesca Ghirga, Donatella Capitani, Luisa Mannina. Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening. Molecules. 2020; 25 (8):1908.
Chicago/Turabian StyleCinzia Ingallina; Anatoly P. Sobolev; Simone Circi; Mattia Spano; Caterina Fraschetti; Antonello Filippi; Antonella Di Sotto; Silvia Di Giacomo; Giulia Mazzoccanti; Francesco Gasparrini; Deborah Quaglio; Enio Campiglia; Simone Carradori; Marcello Locatelli; Giuliana Vinci; Mattia Rapa; Salvatore Ciano; Anna Maria Giusti; Bruno Botta; Francesca Ghirga; Donatella Capitani; Luisa Mannina. 2020. "Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening." Molecules 25, no. 8: 1908.
The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011–2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations.
Andrea Calcaterra; Laura Mangiardi; Giuliano Delle Monache; Deborah Quaglio; Silvia Balducci; Simone Berardozzi; Antonia Iazzetti; Roberta Franzini; Bruno Botta; Francesca Ghirga. The Pictet-Spengler Reaction Updates Its Habits. Molecules 2020, 25, 414 .
AMA StyleAndrea Calcaterra, Laura Mangiardi, Giuliano Delle Monache, Deborah Quaglio, Silvia Balducci, Simone Berardozzi, Antonia Iazzetti, Roberta Franzini, Bruno Botta, Francesca Ghirga. The Pictet-Spengler Reaction Updates Its Habits. Molecules. 2020; 25 (2):414.
Chicago/Turabian StyleAndrea Calcaterra; Laura Mangiardi; Giuliano Delle Monache; Deborah Quaglio; Silvia Balducci; Simone Berardozzi; Antonia Iazzetti; Roberta Franzini; Bruno Botta; Francesca Ghirga. 2020. "The Pictet-Spengler Reaction Updates Its Habits." Molecules 25, no. 2: 414.
: Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to effectively overcome the drug resistance, particularly at the level of Smo. Here, we combined the pharmacophores targeting Smo and Gli1 into a single and individual isoflavone, compound 22, which inhibits the Hh pathway at both upstream and downstream level. We demonstrate that this multitarget agent suppresses medulloblastoma growth in vitro and in vivo through antagonism of Smo and Gli1, which is a novel mechanism of action in Hh inhibition.
Ludovica Lospinoso Severini; Deborah Quaglio; Irene Basili; Francesca Ghirga; Francesca Bufalieri; Miriam Caimano; Silvia Balducci; Marta Moretti; Isabella Romeo; Elena Loricchio; Marella Maroder; Bruno Botta; Mattia Mori; Paola Infante; Lucia Di Marcotullio. A Smo/Gli Multitarget Hedgehog Pathway Inhibitor Impairs Tumor Growth. Cancers 2019, 11, 1518 .
AMA StyleLudovica Lospinoso Severini, Deborah Quaglio, Irene Basili, Francesca Ghirga, Francesca Bufalieri, Miriam Caimano, Silvia Balducci, Marta Moretti, Isabella Romeo, Elena Loricchio, Marella Maroder, Bruno Botta, Mattia Mori, Paola Infante, Lucia Di Marcotullio. A Smo/Gli Multitarget Hedgehog Pathway Inhibitor Impairs Tumor Growth. Cancers. 2019; 11 (10):1518.
Chicago/Turabian StyleLudovica Lospinoso Severini; Deborah Quaglio; Irene Basili; Francesca Ghirga; Francesca Bufalieri; Miriam Caimano; Silvia Balducci; Marta Moretti; Isabella Romeo; Elena Loricchio; Marella Maroder; Bruno Botta; Mattia Mori; Paola Infante; Lucia Di Marcotullio. 2019. "A Smo/Gli Multitarget Hedgehog Pathway Inhibitor Impairs Tumor Growth." Cancers 11, no. 10: 1518.
Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections.
Bruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins 2019, 11, 511 .
AMA StyleBruno Casciaro, Andrea Calcaterra, Floriana Cappiello, Mattia Mori, Maria Loffredo, Francesca Ghirga, Maria Mangoni, Bruno Botta, Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins. 2019; 11 (9):511.
Chicago/Turabian StyleBruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. 2019. "Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections." Toxins 11, no. 9: 511.
Glioma is the most common and primary brain tumors in adults. Despite the available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling is involved in tumorigenesis and emerged as a promising target for brain tumors. Glabrescione B (GlaB) has been recently identified as the first direct inhibitor of Gli1, the downstream effector of the pathway. We established the overexpression of Gli1 in murine glioma cells (GL261) and GlaB effect on cell viability. We used 1H-nuclear magnetic resonance (NMR) metabolomic approach to obtain informative metabolic snapshots of GL261 cells acquired at different time points during GlaB treatment. The activation of AMP activated protein Kinase (AMPK) induced by GlaB was established by western blot. After the orthotopic GL261 cells injection in the right striatum of C57BL6 mice and the intranasal (IN) GlaB/mPEG5kDa-Cholane treatment, the tumor growth was evaluated. The High Performance Liquid Chromatography (HPLC) combined with Mass Spectrometry (MS) was used to quantify GlaB in brain extracts of treated mice. We found that GlaB affected the growth of murine glioma cells both in vitro and in vivo animal model. Using an untargeted 1H-NMR metabolomic approach, we found that GlaB stimulated the glycolytic metabolism in glioma, increasing lactate production. The high glycolytic rate could in part support the cytotoxic effects of GlaB, since the simultaneous blockade of lactate efflux with α-cyano-4-hydroxycinnamic acid (ACCA) affected glioma cell growth. According to the metabolomic data, we found that GlaB increased the phosphorylation of AMPK, a cellular energy sensor involved in the anabolic-to-catabolic transition. Our results indicate that GlaB inhibits glioma cell growth and exacerbates Warburg effect, increasing lactate production. In addition, the simultaneous blockade of Gli1 and lactate efflux amplifies the anti-tumor effect in vivo, providing new potential therapeutic strategy for this brain tumor.
Giuseppina D’Alessandro; Deborah Quaglio; Lucia Monaco; Clotilde Lauro; Francesca Ghirga; Cinzia Ingallina; Michela De Martino; Sergio Fucile; Alessandra Porzia; Maria Amalia Di Castro; Federica Bellato; Francesca Mastrotto; Mattia Mori; Paola Infante; Paola Turano; Stefano Salmaso; Paolo Caliceti; Lucia Di Marcotullio; Bruno Botta; Veronica Ghini; Cristina Limatola. 1H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma. Cell Communication and Signaling 2019, 17, 1 -12.
AMA StyleGiuseppina D’Alessandro, Deborah Quaglio, Lucia Monaco, Clotilde Lauro, Francesca Ghirga, Cinzia Ingallina, Michela De Martino, Sergio Fucile, Alessandra Porzia, Maria Amalia Di Castro, Federica Bellato, Francesca Mastrotto, Mattia Mori, Paola Infante, Paola Turano, Stefano Salmaso, Paolo Caliceti, Lucia Di Marcotullio, Bruno Botta, Veronica Ghini, Cristina Limatola. 1H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma. Cell Communication and Signaling. 2019; 17 (1):1-12.
Chicago/Turabian StyleGiuseppina D’Alessandro; Deborah Quaglio; Lucia Monaco; Clotilde Lauro; Francesca Ghirga; Cinzia Ingallina; Michela De Martino; Sergio Fucile; Alessandra Porzia; Maria Amalia Di Castro; Federica Bellato; Francesca Mastrotto; Mattia Mori; Paola Infante; Paola Turano; Stefano Salmaso; Paolo Caliceti; Lucia Di Marcotullio; Bruno Botta; Veronica Ghini; Cristina Limatola. 2019. "1H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma." Cell Communication and Signaling 17, no. 1: 1-12.
The present review deals with an updated visit to the olefin metathesis reaction as a powerful tool for the construction of sophisticated macromolecular architectures.
Deborah Quaglio; Giovanni Zappia; Elisa De Paolis; Silvia Balducci; Bruno Botta; Francesca Ghirga. Olefin metathesis reaction as a locking tool for macrocycle and mechanomolecule construction. Organic Chemistry Frontiers 2018, 5, 3022 -3055.
AMA StyleDeborah Quaglio, Giovanni Zappia, Elisa De Paolis, Silvia Balducci, Bruno Botta, Francesca Ghirga. Olefin metathesis reaction as a locking tool for macrocycle and mechanomolecule construction. Organic Chemistry Frontiers. 2018; 5 (20):3022-3055.
Chicago/Turabian StyleDeborah Quaglio; Giovanni Zappia; Elisa De Paolis; Silvia Balducci; Bruno Botta; Francesca Ghirga. 2018. "Olefin metathesis reaction as a locking tool for macrocycle and mechanomolecule construction." Organic Chemistry Frontiers 5, no. 20: 3022-3055.
The cover picture shows the mechanistic pathway involved in the ring-opening cross-metathesis (ROM-CM) reaction of resorc[4]arene macrocycles. The red ruthenium atoms lead the way in the formation of a dimeric product, starting from a bicyclic olefin and passing through ruthenium–resorc[4]arene complexes. NMR techniques in combination with organic reaction skills enabled the development of a quantitative analytical protocol for the characterization of the reaction outcome: beside highly strained and unstrained olefins, the macrocycles themselves could be appropriate substrates for “macrocyclization” reactions according to a ROM-CM mechanism. Details are discussed in the Full Paper by B. Botta, G. Uccello-Barretta et al. on page 2407 ff (DOI: 10.1002/ejoc.201601502).
Federica Aiello; Federica Balzano; Francesca Ghirga; Ilaria D'acquarica; Bruno Botta; Gloria Uccello-Barretta; Deborah Quaglio. Front Cover: First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction (Eur. J. Org. Chem. 17/2017). European Journal of Organic Chemistry 2017, 2017, 2385 -2385.
AMA StyleFederica Aiello, Federica Balzano, Francesca Ghirga, Ilaria D'acquarica, Bruno Botta, Gloria Uccello-Barretta, Deborah Quaglio. Front Cover: First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction (Eur. J. Org. Chem. 17/2017). European Journal of Organic Chemistry. 2017; 2017 (17):2385-2385.
Chicago/Turabian StyleFederica Aiello; Federica Balzano; Francesca Ghirga; Ilaria D'acquarica; Bruno Botta; Gloria Uccello-Barretta; Deborah Quaglio. 2017. "Front Cover: First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction (Eur. J. Org. Chem. 17/2017)." European Journal of Organic Chemistry 2017, no. 17: 2385-2385.
For the first time we describe the detection of a ruthenium-carbene-resorc[4]arene complex produced, as a key intermediate, during an olefin metathesis reaction carried out on a resorc[4]arene bicyclic olefin with [Ru(=CHPh)Cl2(PCy3)2] Grubbs first-generation (G1ST) catalyst. The complex was identified by using high-resolution (600 MHz) 1H, 31P NMR and DOSY spectroscopy, in a non-invasive fashion. The singlet at δ = 19.98 ppm (1H NMR), attributed to the alkylidene proton in the G1ST catalyst and that at δ = 53.37 ppm (31P NMR), attributed to the phosphorus atom coordinated with the metal, were selected as probes for a kinetic analysis. The intensity of these signals decreased at the expense of the singlets at 19.26 (1H NMR) and 52.68 ppm (31P NMR), diagnostic for the formation of the ruthenium-carbene-resorc[4]arene complex 3a[Ru]. The resorc[4]arene activated olefin proved to behave as a key propagating species leading to oligomers according to a ROMP pathway.
Federica Aiello; Federica Balzano; Francesca Ghirga; Ilaria D'acquarica; Bruno Botta; Gloria Uccello-Barretta; Deborah Quaglio. First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction. European Journal of Organic Chemistry 2017, 2017, 2407 -2415.
AMA StyleFederica Aiello, Federica Balzano, Francesca Ghirga, Ilaria D'acquarica, Bruno Botta, Gloria Uccello-Barretta, Deborah Quaglio. First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction. European Journal of Organic Chemistry. 2017; 2017 (17):2407-2415.
Chicago/Turabian StyleFederica Aiello; Federica Balzano; Francesca Ghirga; Ilaria D'acquarica; Bruno Botta; Gloria Uccello-Barretta; Deborah Quaglio. 2017. "First Detection of a Ruthenium-Carbene-Resorc[4]arene Complex During the Progress of a Metathesis Reaction." European Journal of Organic Chemistry 2017, no. 17: 2407-2415.
This chapter is aimed at providing an overview of the up-to-now published literature on resorc[4]arene macrocycles exploited as artificial receptors for surface recognition and host-guest chemistry. A concise illustration of the main synthetic strategies developed to afford the resorc[4]arene scaffold is followed by a report on the principles of the investigation of recognition phenomena by nuclear magnetic resonance (NMR), in particular the study of protein-small molecule interactions. Emphasis will be placed on the literature taken largely from our own works on the inhibition of chymotrypsin by suitable N-linked peptidoresorc[4]arenes. Then, the attention was moved towards host-guest studies relying on the entrapment of nitrosonium (NO+) cation inside the cavities of ad hoc functionalized resorc[4]arenes, which yielded both complexes and covalent products. Finally, some recent intriguing resorc[4]arene architectures built up by olefine metathesis reaction occurring between side chains ending with vinylidene groups are presented
Ilaria D’Acquarica; Francesca Ghirga; Cinzia Ingallina; Deborah Quaglio; Giovanni Zappia; Gloria Uccello-Barretta; Federica Balzano; Bruno Botta. Resorc[4]arenes as Preorganized Synthons for Surface Recognition and Host-Guest Chemistry. Calixarenes and Beyond 2016, 175 -193.
AMA StyleIlaria D’Acquarica, Francesca Ghirga, Cinzia Ingallina, Deborah Quaglio, Giovanni Zappia, Gloria Uccello-Barretta, Federica Balzano, Bruno Botta. Resorc[4]arenes as Preorganized Synthons for Surface Recognition and Host-Guest Chemistry. Calixarenes and Beyond. 2016; ():175-193.
Chicago/Turabian StyleIlaria D’Acquarica; Francesca Ghirga; Cinzia Ingallina; Deborah Quaglio; Giovanni Zappia; Gloria Uccello-Barretta; Federica Balzano; Bruno Botta. 2016. "Resorc[4]arenes as Preorganized Synthons for Surface Recognition and Host-Guest Chemistry." Calixarenes and Beyond , no. : 175-193.
This review is aimed at providing an overview of the up-to-now published literature on resorc[4]arene macrocycles exploited as artificial receptors for the molecular recognition of some classes of natural products. A concise illustration of the main synthetic strategies developed to afford the resorc[4]arene scaffold is followed by a report on the principles of the gas-phase investigation of recognition phenomena by mass spectrometry (MS). Emphasis is placed on gas-phase studies of diastereoisomeric complexes generated inside a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer by resorc[4]arene receptors towards a series of natural products, namely amino acids, amphetamine, ethanolamine neurotransmitters, dipeptides, vinca alkaloids and nucleosides. The literature outcomes discussed here, taken largely from our own revisited work, have been completed by references to other studies, in order to draw a broader picture of this rapidly evolving field of research
Ilaria D`acquarica; Francesca Ghirga; Deborah Quaglio; Antonella Cerreto; Cinzia Ingallina; Andrea Tafi; Bruno Botta. Molecular Recognition of Natural Products by Resorc[4]arene Receptors. Current Pharmaceutical Design 2016, 22, 1715 -1729.
AMA StyleIlaria D`acquarica, Francesca Ghirga, Deborah Quaglio, Antonella Cerreto, Cinzia Ingallina, Andrea Tafi, Bruno Botta. Molecular Recognition of Natural Products by Resorc[4]arene Receptors. Current Pharmaceutical Design. 2016; 22 (12):1715-1729.
Chicago/Turabian StyleIlaria D`acquarica; Francesca Ghirga; Deborah Quaglio; Antonella Cerreto; Cinzia Ingallina; Andrea Tafi; Bruno Botta. 2016. "Molecular Recognition of Natural Products by Resorc[4]arene Receptors." Current Pharmaceutical Design 22, no. 12: 1715-1729.
Ring-closing metathesis (RCM) catalyzed by a second-generation Grubbs catalyst has been used to synthesize resorc[4]arenes 2b-5b starting from undecenyl resorc[4]arene 1b fixed in the cone conformation. X-ray diffraction analysis of the major metathesis product, 3b (50% yield), revealed a cavity-shaped architecture resembling a basket, endowed with a large intramolecular space (∼10 Å) and a strong propensity to self-assemble as a supramolecular trio of heterochiral dimers. This prompted us to investigate the aggregation propensity of basket 3b in THF/water solution by UV-visible spectroscopy. The cavitation Gibbs free-energy change (ΔΔGcav = 4.78 kcal mol(-1)) associated with the self-assembly of macrocycle 3b was calculated as a measure of the solvophobic interactions involved in the process.
Francesca Ghirga; Deborah Quaglio; Valentina Iovine; Bruno Botta; Marco Pierini; Luisa Mannina; Anatoly P. Sobolev; Franco Ugozzoli; Ilaria D’Acquarica. Synthesis of a Double-Spanned Resorc[4]arene via Ring-Closing Metathesis and Calculation of Aggregation Propensity. The Journal of Organic Chemistry 2014, 79, 11051 -11060.
AMA StyleFrancesca Ghirga, Deborah Quaglio, Valentina Iovine, Bruno Botta, Marco Pierini, Luisa Mannina, Anatoly P. Sobolev, Franco Ugozzoli, Ilaria D’Acquarica. Synthesis of a Double-Spanned Resorc[4]arene via Ring-Closing Metathesis and Calculation of Aggregation Propensity. The Journal of Organic Chemistry. 2014; 79 (22):11051-11060.
Chicago/Turabian StyleFrancesca Ghirga; Deborah Quaglio; Valentina Iovine; Bruno Botta; Marco Pierini; Luisa Mannina; Anatoly P. Sobolev; Franco Ugozzoli; Ilaria D’Acquarica. 2014. "Synthesis of a Double-Spanned Resorc[4]arene via Ring-Closing Metathesis and Calculation of Aggregation Propensity." The Journal of Organic Chemistry 79, no. 22: 11051-11060.