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The cis-stereoisomers of Δ9-THC [(−)-3 and (+)-3] were identified and quantified in a series of low-THC-containing varieties of Cannabis sativa registered in Europe as fiber hemp and in research accessions of cannabis. While Δ9-cis-THC (3) occurs in cannabis fiber hemp in the concentration range of (−)-Δ9-trans-THC [(−)-1], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ9-cis-THC (3) is scalemic (ca. 80–90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR [(−)-3] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (−)-Δ9-cis-THC [(−)-3], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of “Δ9-THC and isomers” and needs therefore revision, or at least a more specific wording, to account for the presence of Δ9-cis-THCs [(+)-3 and (−)-3] in cannabis fiber hemp varieties.
Michael A. Schafroth; Giulia Mazzoccanti; Ines Reynoso-Moreno; Reto Erni; Federica Pollastro; Diego Caprioglio; Bruno Botta; Gianna Allegrone; Giulio Grassi; Andrea Chicca; Francesco Gasparrini; Jürg Gertsch; Erick M. Carreira; Giovanni Appendino. Δ9-cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology. Journal of Natural Products 2021, 1 .
AMA StyleMichael A. Schafroth, Giulia Mazzoccanti, Ines Reynoso-Moreno, Reto Erni, Federica Pollastro, Diego Caprioglio, Bruno Botta, Gianna Allegrone, Giulio Grassi, Andrea Chicca, Francesco Gasparrini, Jürg Gertsch, Erick M. Carreira, Giovanni Appendino. Δ9-cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology. Journal of Natural Products. 2021; ():1.
Chicago/Turabian StyleMichael A. Schafroth; Giulia Mazzoccanti; Ines Reynoso-Moreno; Reto Erni; Federica Pollastro; Diego Caprioglio; Bruno Botta; Gianna Allegrone; Giulio Grassi; Andrea Chicca; Francesco Gasparrini; Jürg Gertsch; Erick M. Carreira; Giovanni Appendino. 2021. "Δ9-cis-Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology." Journal of Natural Products , no. : 1.
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.
Andrea Calcaterra; Giancarlo Fabrizi; Bruno Botta; Juan Jose Guevara. Convergent total synthesis of (±)-kuwanol E. 2021, 1 .
AMA StyleAndrea Calcaterra, Giancarlo Fabrizi, Bruno Botta, Juan Jose Guevara. Convergent total synthesis of (±)-kuwanol E. . 2021; ():1.
Chicago/Turabian StyleAndrea Calcaterra; Giancarlo Fabrizi; Bruno Botta; Juan Jose Guevara. 2021. "Convergent total synthesis of (±)-kuwanol E." , no. : 1.
Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.
Yue Zheng; Xian-Wen Yang; Dominique Schols; Mattia Mori; Bruno Botta; Andy Chevigné; Martin Mulinge; André Steinmetz; Jean-Claude Schmit; Carole Seguin-Devaux. Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action. International Journal of Molecular Sciences 2021, 22, 5052 .
AMA StyleYue Zheng, Xian-Wen Yang, Dominique Schols, Mattia Mori, Bruno Botta, Andy Chevigné, Martin Mulinge, André Steinmetz, Jean-Claude Schmit, Carole Seguin-Devaux. Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action. International Journal of Molecular Sciences. 2021; 22 (9):5052.
Chicago/Turabian StyleYue Zheng; Xian-Wen Yang; Dominique Schols; Mattia Mori; Bruno Botta; Andy Chevigné; Martin Mulinge; André Steinmetz; Jean-Claude Schmit; Carole Seguin-Devaux. 2021. "Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action." International Journal of Molecular Sciences 22, no. 9: 5052.
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.
Colistin is a last-resort antibiotic for treatment of multidrug resistant Gram-negative bacterial infections. Recently, a natural ent-beyerene diterpene was identified as a promising inhibitor of the enzyme responsible for colistin re-sistance mediated by lipid A aminoarabinosylation, in Gram-negative bacteria, namely ArnT (undecaprenyl phospha-te-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase). Here, semi-synthetic analogs of hit were designed, synthetized and tested against colistin-resistant Pseudomonas aeruginosa strains including clinical isolates, to exploit the versatility of the diterpene scaffold. Microbiological assays coupled with molecular modeling indicated that for a more efficient colistin adjuvant activity, likely resulting from inhibition of the ArnT activity by the selected com-pounds and therefore from their interaction with the catalytic site of ArnT, an ent-beyerane scaffold is required along with an oxalate like group at C-18/C-19, or a sugar residue at C-19 to resemble L-Ara4N. The ent-beyerane skeleton is identified for the first time as a privileged scaffold for further cost-effective development of valuable colistin re-sistance inhibitors.
Deborah Quaglio; Maria Luisa Mangoni; Roberta Stefanelli; Silvia Corradi; Bruno Casciaro; Valeria Vergine; Federica Lucantoni; Luca Cavinato; Silvia Cammarone; Maria Rosa Loffredo; Floriana Cappiello; Andrea Calcaterra; Silvia Erazo; Francesca Ghirga; Mattia Mori; Francesco Imperi; Fiorentina Ascenzioni; Bruno Botta. ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors. The Journal of Organic Chemistry 2020, 85, 10891 -10901.
AMA StyleDeborah Quaglio, Maria Luisa Mangoni, Roberta Stefanelli, Silvia Corradi, Bruno Casciaro, Valeria Vergine, Federica Lucantoni, Luca Cavinato, Silvia Cammarone, Maria Rosa Loffredo, Floriana Cappiello, Andrea Calcaterra, Silvia Erazo, Francesca Ghirga, Mattia Mori, Francesco Imperi, Fiorentina Ascenzioni, Bruno Botta. ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors. The Journal of Organic Chemistry. 2020; 85 (16):10891-10901.
Chicago/Turabian StyleDeborah Quaglio; Maria Luisa Mangoni; Roberta Stefanelli; Silvia Corradi; Bruno Casciaro; Valeria Vergine; Federica Lucantoni; Luca Cavinato; Silvia Cammarone; Maria Rosa Loffredo; Floriana Cappiello; Andrea Calcaterra; Silvia Erazo; Francesca Ghirga; Mattia Mori; Francesco Imperi; Fiorentina Ascenzioni; Bruno Botta. 2020. "ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors." The Journal of Organic Chemistry 85, no. 16: 10891-10901.
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.
Deborah Quaglio; Laura Mangiardi; Giulia Venditti; Cristina Del Plato; Francesca Polli; Francesca Ghirga; Gabriele Favero; Marco Pierini; Bruno Botta; Franco Mazzei. Cover Feature: Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors (Chem. Eur. J. 38/2020). Chemistry – A European Journal 2020, 26, 8317 -8317.
AMA StyleDeborah Quaglio, Laura Mangiardi, Giulia Venditti, Cristina Del Plato, Francesca Polli, Francesca Ghirga, Gabriele Favero, Marco Pierini, Bruno Botta, Franco Mazzei. Cover Feature: Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors (Chem. Eur. J. 38/2020). Chemistry – A European Journal. 2020; 26 (38):8317-8317.
Chicago/Turabian StyleDeborah Quaglio; Laura Mangiardi; Giulia Venditti; Cristina Del Plato; Francesca Polli; Francesca Ghirga; Gabriele Favero; Marco Pierini; Bruno Botta; Franco Mazzei. 2020. "Cover Feature: Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors (Chem. Eur. J. 38/2020)." Chemistry – A European Journal 26, no. 38: 8317-8317.
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.
Silymarin is the standardized extract from the fruits of Silybum marianum (L.) Gaertn., a well-known hepatoprotectant and antioxidant. Recently, bioactive compounds of silymarin, i.e., silybins and their 2,3-dehydro derivatives, have been shown to exert anticancer activities, yet with unclear mechanisms. This study combines in silico and in vitro methods to reveal the potential interactions of optically pure silybins and dehydrosilybins with novel protein targets. The shape and chemical similarity with approved drugs were evaluated in silico, and the potential for interaction with the Hedgehog pathway receptor Smoothened (SMO) and BRAF kinase was confirmed by molecular docking. In vitro studies on SMO and BRAF V600E kinase activity and in BRAF V600E A-375 human melanoma cell lines were further performed to examine their effects on these proteins and cancer cell lines and to corroborate computational predictions. Our in silico results direct to new potential targets of silymarin constituents as dual inhibitors of BRAF and SMO, two major targets in anticancer therapy. The experimental studies confirm that BRAF kinase and SMO may be involved in mechanisms of anticancer activities, demonstrating dose-dependent profiles, with dehydrosilybins showing stronger effects than silybins. The results of this work outline the dual SMO/BRAF effect of flavonolignans from Silybum marianum with potential clinical significance. Our approach can be applied to other natural products to reveal their potential targets and mechanism of action.
Antonia Diukendjieva; Maya M. Zaharieva; Mattia Mori; Petko Alov; Ivanka Tsakovska; Tania Pencheva; Hristo Najdenski; Vladimír Křen; Chiara Felici; Francesca Bufalieri; Lucia Di Marcotullio; Bruno Botta; Maurizio Botta; Ilza Pajeva. Dual SMO/BRAF Inhibition by Flavonolignans from Silybum marianum. Antioxidants 2020, 9, 384 .
AMA StyleAntonia Diukendjieva, Maya M. Zaharieva, Mattia Mori, Petko Alov, Ivanka Tsakovska, Tania Pencheva, Hristo Najdenski, Vladimír Křen, Chiara Felici, Francesca Bufalieri, Lucia Di Marcotullio, Bruno Botta, Maurizio Botta, Ilza Pajeva. Dual SMO/BRAF Inhibition by Flavonolignans from Silybum marianum. Antioxidants. 2020; 9 (5):384.
Chicago/Turabian StyleAntonia Diukendjieva; Maya M. Zaharieva; Mattia Mori; Petko Alov; Ivanka Tsakovska; Tania Pencheva; Hristo Najdenski; Vladimír Křen; Chiara Felici; Francesca Bufalieri; Lucia Di Marcotullio; Bruno Botta; Maurizio Botta; Ilza Pajeva. 2020. "Dual SMO/BRAF Inhibition by Flavonolignans from Silybum marianum." Antioxidants 9, no. 5: 384.
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.
One of the main problems in the development of immunosensors is to overcome the complexity of binding antibody to the sensor surface. Most of immobilizing methods lead to a random orientation of antibodies with a lower binding site density and immunoaffinity. In order to control the orientation of antibody immobilization, several resorc[4]arene derivatives were designed and synthesized. After the spectroscopic characterization of resorc[4]arene self‐assembled monolayers (SAMs) onto gold films, the surface coverage and the orientation of insulin antibody (Ab‐Ins) were assessed by Surface Plasmon Resonance (SPR) technique and compared with a random immobilization method. Experimental results combined with theoretical studies confirmed the dipole‐dipole interaction as an important factor in antibody orientation and demonstrated the importance of the upper rim functionalization of resorcarenes. Accordingly, resorcarene 5 showed a major binding force towards Ab‐Ins thanks to the H‐bond interactions with the amine protein groups. Based on these findings, the resorcarene‐based immunosensor is a powerful system with improved sensitivity providing new insight into sensors development.
Deborah Quaglio; Laura Mangiardi; Giulia Venditti; Cristina Del Plato; Francesca Polli; Francesca Ghirga; Gabriele Favero; Marco Pierini; Bruno Botta; Franco Mazzei. Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors. Chemistry – A European Journal 2020, 26, 8400 -8406.
AMA StyleDeborah Quaglio, Laura Mangiardi, Giulia Venditti, Cristina Del Plato, Francesca Polli, Francesca Ghirga, Gabriele Favero, Marco Pierini, Bruno Botta, Franco Mazzei. Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors. Chemistry – A European Journal. 2020; 26 (38):8400-8406.
Chicago/Turabian StyleDeborah Quaglio; Laura Mangiardi; Giulia Venditti; Cristina Del Plato; Francesca Polli; Francesca Ghirga; Gabriele Favero; Marco Pierini; Bruno Botta; Franco Mazzei. 2020. "Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors." Chemistry – A European Journal 26, no. 38: 8400-8406.
Introduction: Hedgehog (Hh) signaling plays a pivotal role in tissue development and stemness, and its deregulation is found in many different tumors. Several efforts have been devoted to discovery of Hh inhibitors, including three drugs approved by the Food and Drug Administration (FDA), targeting the upstream receptor smoothened (SMO). However, SMO mutations or SMO-independent Hh pathway activation raise the need for novel Hh inhibitors. Areas covered: This review describes Hh inhibitors with anticancer potential patented in the period 2015–present. Expert opinion: Despite the initial enthusiasm in SMO antagonists, drug-resistant mutations, and SMO-independent Hh activation limited their clinical application. A growing number of therapeutic strategies are currently focusing on downstream Hh effectors (i.e. glioma-associate oncogenes (GLI) proteins) or other signaling pathways related to Hh, in addition to drug repositioning. Given the heterogenic nature of cancers, a terrific clinical impact is expected by multi-targeting approaches able to modulate simultaneously SMO and GLI, and/or additional targets that act as regulators of Hh signaling. It is expected that these alternative strategies might be investigated in clinical trials in the next years against a wide variety of tumor types, and that they provide improved outcomes compared to current SMO antagonists or other single-agent anticancer drugs.
Deborah Quaglio; Paola Infante; Lucia Di Marcotullio; Bruno Botta; Mattia Mori. Hedgehog signaling pathway inhibitors: an updated patent review (2015–present). Expert Opinion on Therapeutic Patents 2020, 30, 235 -250.
AMA StyleDeborah Quaglio, Paola Infante, Lucia Di Marcotullio, Bruno Botta, Mattia Mori. Hedgehog signaling pathway inhibitors: an updated patent review (2015–present). Expert Opinion on Therapeutic Patents. 2020; 30 (4):235-250.
Chicago/Turabian StyleDeborah Quaglio; Paola Infante; Lucia Di Marcotullio; Bruno Botta; Mattia Mori. 2020. "Hedgehog signaling pathway inhibitors: an updated patent review (2015–present)." Expert Opinion on Therapeutic Patents 30, no. 4: 235-250.
Novel diterpenoids were isolated from the extracts of Fabiana densa var. ramulosa and found to display a selective activity against Gram-positive bacterial strains with negligible cytotoxicity toward human keratinocytes. This study highlighted the role played by the acidic group at C18 of the tetracyclic ent-beyerene scaffold for antibacterial effects and how the length and flexibility of the alkyl chain between the two carbonyl groups are crucial factors to increase the antimicrobial activity of the molecules, supporting the development of natural products from F. densa and their derivatives for treatment of microbial infections.
Deborah Quaglio; Silvia Corradi; Silvia Erazo; Valeria Vergine; Simone Berardozzi; Fabio Sciubba; Floriana Cappiello; Maria Elisa Crestoni; Fiorentina Ascenzioni; Francesco Imperi; Franco Delle Monache; Mattia Mori; Maria Rosa Loffredo; Francesca Ghirga; Bruno Casciaro; Bruno Botta; Maria Luisa Mangoni. Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa. ACS Medicinal Chemistry Letters 2020, 11, 760 -765.
AMA StyleDeborah Quaglio, Silvia Corradi, Silvia Erazo, Valeria Vergine, Simone Berardozzi, Fabio Sciubba, Floriana Cappiello, Maria Elisa Crestoni, Fiorentina Ascenzioni, Francesco Imperi, Franco Delle Monache, Mattia Mori, Maria Rosa Loffredo, Francesca Ghirga, Bruno Casciaro, Bruno Botta, Maria Luisa Mangoni. Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa. ACS Medicinal Chemistry Letters. 2020; 11 (5):760-765.
Chicago/Turabian StyleDeborah Quaglio; Silvia Corradi; Silvia Erazo; Valeria Vergine; Simone Berardozzi; Fabio Sciubba; Floriana Cappiello; Maria Elisa Crestoni; Fiorentina Ascenzioni; Francesco Imperi; Franco Delle Monache; Mattia Mori; Maria Rosa Loffredo; Francesca Ghirga; Bruno Casciaro; Bruno Botta; Maria Luisa Mangoni. 2020. "Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa." ACS Medicinal Chemistry Letters 11, no. 5: 760-765.
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.
Mattia Mori; Fabrizio Manetti; Bruno Botta; Andrea Tafi. In Memory of Maurizio Botta: His Contribution to the Development of Computer-Aided Drug Design. Journal of Chemical Information and Modeling 2019, 59, 4961 -4967.
AMA StyleMattia Mori, Fabrizio Manetti, Bruno Botta, Andrea Tafi. In Memory of Maurizio Botta: His Contribution to the Development of Computer-Aided Drug Design. Journal of Chemical Information and Modeling. 2019; 59 (12):4961-4967.
Chicago/Turabian StyleMattia Mori; Fabrizio Manetti; Bruno Botta; Andrea Tafi. 2019. "In Memory of Maurizio Botta: His Contribution to the Development of Computer-Aided Drug Design." Journal of Chemical Information and Modeling 59, no. 12: 4961-4967.
Candida albicans biofilm is associated with high rates of morbidity and resistance to antifungals. The aim of the present study is to evaluate the anti-Candida albicans biofilm activity of some indigenous Algerian medicinal plant extracts: Clematis flammula and Fraxinus angustifolia and their influence on the virulence factors of C. albicans. The anti-biofilm activity was determined using crystal violet assay while the cell surface hydrophobicity (CSH) was estimated in a water-hydrocarbon two-phase assay. Moreover, germ tube formation and hyphae elongation were assessed microscopically. F. angustifolia leaves and bark, as well as C. flammula leaves extracts (500 μg/mL) showed an inhibition of biofilm formation of 62.41 ± 3.88, 54.83 ± 0.98 and 36.78 ± 1.09%, respectively, probably related to a disruption of CSH, germ tube and hyphae formation of C. albicans ATCC 10231 (p < 0.001). Phytochemical analysis revealed that the plant extracts were a rich source of phenolic compounds with the highest content found in F. angustifolia leaves (173.05 ± 0.15 mg gallic acid equivalent per gram of extract), which could explain its highest efficiency against biofilm activity. Considering the results obtained, it can be concluded that the plants tested could be a promising source of drugs against muco-cutaneous infections caused by C. albicans biofilm.
Asma Ourabah; Dina Atmani-Kilani; Nadjet Debbache-Benaida; Olga Kolesova; Lila Azib; Farah Yous; Malika Benloukil; Bruno Botta; Djebbar Atmani; Giovanna Simonetti. Anti-Candida albicans biofilm activity of extracts from two selected indigenous Algerian plants: Clematis flammula and Fraxinus angustifolia. Journal of Herbal Medicine 2019, 20, 100319 .
AMA StyleAsma Ourabah, Dina Atmani-Kilani, Nadjet Debbache-Benaida, Olga Kolesova, Lila Azib, Farah Yous, Malika Benloukil, Bruno Botta, Djebbar Atmani, Giovanna Simonetti. Anti-Candida albicans biofilm activity of extracts from two selected indigenous Algerian plants: Clematis flammula and Fraxinus angustifolia. Journal of Herbal Medicine. 2019; 20 ():100319.
Chicago/Turabian StyleAsma Ourabah; Dina Atmani-Kilani; Nadjet Debbache-Benaida; Olga Kolesova; Lila Azib; Farah Yous; Malika Benloukil; Bruno Botta; Djebbar Atmani; Giovanna Simonetti. 2019. "Anti-Candida albicans biofilm activity of extracts from two selected indigenous Algerian plants: Clematis flammula and Fraxinus angustifolia." Journal of Herbal Medicine 20, no. : 100319.