98 results on '"Della Sala G"'
Search Results
2. Extremal and Stationary Discs for the Kobayashi k -Metric
- Author
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Bertrand, F., primary, Della Sala, G., additional, and Joo, J.-C., additional
- Published
- 2020
- Full Text
- View/download PDF
3. Extremal and Stationary Discs for the Kobayashi $k$ -Metric
- Author
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Bertrand, F., primary, Della Sala, G., additional, and Joo, J.-C., additional
- Published
- 2019
- Full Text
- View/download PDF
4. Total Synthesis of Bioactive Peptides and Depsipeptides from Marine Opisthobranch Molluscs
- Author
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Della Monica, C., primary, Della Sala, G., additional, De Riccardis, F., additional, Izzo, I., additional, and Spinella, Aldo, additional
- Published
- 2006
- Full Text
- View/download PDF
5. Asymmetric Phase-Transfer Catalysis by Chiral Calix[4]arene Derivatives
- Author
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De Simone, N. A., Schettini, R., Talotta, C., Gaeta, C., Izzo, I., De Riccardis, F., Della Sala, G., and Neri, P.
- Published
- 2017
6. Tuning the biomimetic performances of 4-hydroxyproline-containing cyclic peptoids
- Author
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Schettini, R., primary, Costabile, C., additional, Della Sala, G., additional, Buirey, J., additional, Tosolini, M., additional, Tecilla, P., additional, Vaccaro, M. C., additional, Bruno, I., additional, De Riccardis, F., additional, and Izzo, I., additional
- Published
- 2018
- Full Text
- View/download PDF
7. Conformational isomerism in cyclic peptoids and its specification
- Author
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D'Amato, A., primary, Schettini, R., additional, Della Sala, G., additional, Costabile, C., additional, Tedesco, C., additional, Izzo, I., additional, and De Riccardis, F., additional
- Published
- 2017
- Full Text
- View/download PDF
8. Synthesis and complexing properties of cyclic benzylopeptoids – a new family of extended macrocyclic peptoids
- Author
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Meli, A., primary, Gambaro, S., additional, Costabile, C., additional, Talotta, C., additional, Della Sala, G., additional, Tecilla, P., additional, Milano, D., additional, Tosolini, M., additional, Izzo, I., additional, and De Riccardis, F., additional
- Published
- 2016
- Full Text
- View/download PDF
9. Highly enantioselective organocatalytic desymmetrization of meso-aziridines by trialkylsilylchalcogenides
- Author
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Della Sala, G., Lattanzi, A., Santoro, Stefano, and Santi, Claudio
- Published
- 2009
10. Towards the biosynthesis of the aromatic products of the Mediterranean mollusc Scaphander lignarius: isolation and synthesis of analogues of lignarenones
- Author
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Della Sala G., Cutignano A., Calabrese G, Spinella A, Domenech Coll A., dIppolito G., Cimino G, and Fontana A.
- Published
- 2007
11. Corrigendum to Enantioselective Synthesis of 1 (R)-Hydroxypolygodial
- Author
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DELLA MONICA, C, DELLA SALA, G, Durso, D, Izzo, Irene, and Spinella, Aldo
- Published
- 2006
12. Isolation, structure determination and synthesis of new metabolites from the marine mollusc Scaphander lignarius
- Author
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Fontana, Cutignano A., Cimino G., Domenech A., Ballesteros M., Calabrese G., Della Sala G., and Spinella A.
- Published
- 2004
13. Synthesis of antifungal N-isoprenyl-indol alkaloids from the fungus Aporpium caryae
- Author
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Della Sala G., Capozzo D., Izzo I., Giordano A., Iommazzo A., and Spinella A.
- Published
- 2002
14. ChemInform Abstract: Synthesis of Calicoferol E and Astrogorgiadiol, Two Marine 9,10-Secosteroids
- Author
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DELLA SALA, G., primary, IZZO, I., additional, DE RICCARDIS, F., additional, and SODANO, G., additional
- Published
- 2010
- Full Text
- View/download PDF
15. Total Synthesis of Bioreactive Peptides and Depsipeptides from Marine Opisthobranch Molluscs
- Author
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Della Monica, C., primary, Della Sala, G., additional, De Riccardis, F., additional, Izzo, I., additional, and Spinella, A., additional
- Published
- 2007
- Full Text
- View/download PDF
16. Assessment of visual function in MS patients: comparative study of same diagnostic tests
- Author
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MARTINELLI V, LOCATELLI T, DELLA SALA G, SOMAZZI L., COMI , GIANCARLO, Martinelli, V, Comi, Giancarlo, Locatelli, T, DELLA SALA, G, and Somazzi, L.
- Published
- 1987
17. Synaptic alterations in animal models of Rett syndrome.
- Author
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Pizzorusso, T., Boggio, E. M., Della Sala, G., Giustetto, M., Lonetti, G., and Putignano, E.
- Subjects
NEUROTRANSMITTERS ,INTELLECTUAL disabilities ,COMPARATIVE pathology - Abstract
There is mounting evidence showing that the structural and molecular organization of synaptic connections is affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synaptopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett syndrome (RS). RS (MIM312750) is an X-linked dominant neurological disorder that is caused in the majority of cases by mutations in methylCpG-binding protein 2 (MeCP2). We will discuss recent data characterizing synaptic alterations in animal models of RS and their regulation by environmental and molecular factors. [ABSTRACT FROM AUTHOR]
- Published
- 2013
18. ChemInform Abstract: Synthesis of Calicoferol E and Astrogorgiadiol, Two Marine 9,10-Secosteroids.
- Author
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DELLA SALA, G., IZZO, I., DE RICCARDIS, F., and SODANO, G.
- Published
- 1998
- Full Text
- View/download PDF
19. High N‐H Photoacidity of a Nitrogen‐Rich Fused Ring Heteroaromatic Scaffold
- Author
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Roberto Centore, Assunta D'Amato, Giorgio Della Sala, Mariangela Di Donato, Alessandro Landi, Carla Manfredi, Andrea Peluso, Centore, R., D'Amato, A., Della Sala, G., Di Donato, M., Landi, A., Manfredi, C., and Peluso, A.
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Organic Chemistry ,Physical and Theoretical Chemistry ,Analytical Chemistry - Abstract
It is shown that 4-methyl-7-(4-nitrophenyl)-triazolo[3,2-c]triazole exhibits a high photoacidity, unprecedented in neutral molecules in which the proton is delivered by a NH bond, which promotes acetalization of aldehydes under irradiation by a near-UV low power LED. Time dependent transient absorption spectroscopy shows a series of stimulated emission signals attributable to photo-tautomerization and formation of the deprotonated species, followed by broad positive absorption band which does not decay within the investigated timescale, compatible with the formation of a long living species, possibly the anion in the lowest energy triplet state. Computational analyses qualitatively confirm the strong photoacidity of the molecule in all its tautomeric forms, allow to assign transient absorption signals, and show that the first singlet excited state exhibits high spin-orbit couplings with excited triplet states which could promote a fast singlet-triplet transition, thus leading to a long living species able to photocatalyze chemical reactions.
- Published
- 2023
20. Mixotrophy in a Local Strain of Nannochloropsis granulata for Renewable High-Value Biomass Production on the West Coast of Sweden
- Author
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Valeria Villanova, Christian Galasso, Giovanni Andrea Vitale, Gerardo Della Sala, Johan Engelbrektsson, Niklas Strömberg, Kashif Mohd Shaikh, Mats X. Andersson, Fortunato Palma Esposito, Susanne Ekendahl, Donatella De Pascale, Cornelia Spetea, Villanova V., Galasso C., Vitale G.A., Della Sala G., Engelbrektsson J., Stromberg N., Shaikh K.M., Andersson M.X., Esposito F.P., Ekendahl S., De Pascale D., and Spetea C.
- Subjects
antitumoral activity ,microalgae ,carotenoids ,Pharmaceutical Science ,metabolomics ,photobioreactors ,mixotrophy ,Drug Discovery ,Nannochloropsis ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,bioassay analysis ,cell death pathway ,polyunsaturated fatty acids ,CHN analysis ,bioassay ,autophagy - Abstract
A local strain of Nannochloropsis granulata (Ng) has been reported as the most productive microalgal strain in terms of both biomass yield and lipid content when cultivated in photobioreactors that simulate the light and temperature conditions during the summer on the west coast of Sweden. To further increase the biomass and the biotechnological potential of this strain in these conditions, mixotrophic growth (i.e., the simultaneous use of photosynthesis and respiration) with glycerol as an external carbon source was investigated in this study and compared with phototrophic growth that made use of air enriched with 1–2% CO2. The addition of either glycerol or CO2-enriched air stimulated the growth of Ng and theproduction of high-value long-chain polyunsaturated fatty acids (EPA) as well as the carotenoid canthaxanthin. Bioassays in human prostate cell lines indicated the highest antitumoral activity for Ng extracts and fractions from mixotrophic conditions. Metabolomics detected betaine lipids specifically in the bioactive fractions, suggesting their involvement in the observed antitumoral effect. Genes related to autophagy were found to be upregulated by the most bioactive fraction, suggesting a possible therapeutic target against prostate cancer progression. Taken together, our results suggest that the local Ng strain can be cultivated mixotrophically in summer conditions on the west coast of Sweden for the production of high-value biomass containing antiproliferative compounds, carotenoids, and EPA.
- Published
- 2022
- Full Text
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21. Role of Lipophilicity in the Activity of Hexameric Cyclic Peptoid Ion Carriers
- Author
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Massimo Tosolini, Giorgio Della Sala, Paolo Tecilla, Consiglia Tedesco, Giovanni Pierri, Irene Izzo, Muhammed Raza Shah, Rosaria Schettini, Jawad ur Rehman, Francesco De Riccardis, Schettini, R., Tosolini, M., ur Rehman, J., Shah, M. R., Pierri, G., Tedesco, C., Della Sala, G., De Riccardis, F., Tecilla, P., and Izzo, I.
- Subjects
Ionophores ,Ion carriers ,Chemistry ,Peptidomimetic ,Organic Chemistry ,Peptoid ,Ion carrier ,Combinatorial chemistry ,chemistry.chemical_compound ,Macrocycle ,Cyclic peptoids ,Macrocycles ,Peptidomimetics ,Ionophore ,Lipophilicity ,Cyclic peptoid ,Physical and Theoretical Chemistry - Abstract
Two families of hexameric cyclic peptoids decorated with linear N-alkyl and alternated N-alkyl/N-benzyl side chains (2 a–d and 3 a–c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4
- Published
- 2020
22. New Tricks with an Old Sponge: Feature-Based Molecular Networking Led to Fast Identification of New Stylissamide L from Stylissa caribica
- Author
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Joseph R. Pawlik, Gerardo Della Sala, Silvia Scarpato, Roberta Teta, Valeria Costantino, Alfonso Mangoni, Scarpato, S., Teta, R., Della Sala, G., Pawlik, J. R., Costantino, V., and Mangoni, A.
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Stereochemistry ,Large array ,Pharmaceutical Science ,01 natural sciences ,cyclic peptide ,03 medical and health sciences ,feature-based molecular networking ,Drug Discovery ,Feature based ,Proline ,marine sponges ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,lcsh:QH301-705.5 ,030304 developmental biology ,Cell growth inhibitor ,chemistry.chemical_classification ,0303 health sciences ,molecular networking ,biology ,010405 organic chemistry ,Chemistry ,cyclic peptides ,biology.organism_classification ,dereplication ,metabolomics ,Cyclic peptide ,0104 chemical sciences ,Sponge ,lcsh:Biology (General) ,Molecular networking ,proline-rich peptides ,Cancer cell lines ,marine sponge ,metabolomic - Abstract
Feature-based molecular networking was used to re-examine the secondary metabolites in extracts of a very well studied marine sponge, Stylissa caribica, known to contain a large array of cyclic peptides and brominated alkaloids. The analysis revealed the presence of 13 cyclic peptides in the sponge that had never been detected in previous work and appeared to be new compounds. The most abundant one was isolated and shown to be a new proline-rich cyclic heptapetide that was called stylissamide L (1). Structure of compound 1, including the cis/trans geometry of the three proline residues, was determined by extensive NMR studies, the l configuration of the seven amino acid residues was determined using Marfey&rsquo, s method. Stylissamide L was tested for activity as a cell growth inhibitor and cell migration inhibitor on two cancer cell lines but, unlike other members of the stylissamide family, it showed no significant activity. This approach showed that even a thoroughly studied species such as S. caribica may contain new chemistry that can be revealed if studied with the right tools.
- Published
- 2020
23. Binding of the Anti-FIV Peptide C8 to Differently Charged Membrane Models: From First Docking to Membrane Tubulation
- Author
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Paolo Remondelli, Ornella Moltedo, Mario Scrima, Giuseppina Amodio, Gerardino D'Errico, Alice Romagnoli, Vittorio Limongelli, Ilaria Stillitano, Grazia Della Sala, Manuela Grimaldi, Giovanni Boccia, Daniele Di Marino, Anna Maria D'Ursi, Augusta De Santis, Agostino Bruno, Di Marino, D., Bruno, A., Grimaldi, M., Scrima, M., Stillitano, I., Amodio, G., Della Sala, G., Romagnoli, A., De Santis, A., Moltedo, O., Remondelli, P., Boccia, G., D'Errico, G., D'Ursi, A. M., and Limongelli, V.
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FIV ,HIV ,membrane tubulation ,molecular dynamics ,MPER ,NMR ,peptide/membrane binding ,umbrella sampling ,Phospholipid ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,lcsh:Chemistry ,Cell membrane ,chemistry.chemical_compound ,medicine ,Lipid bilayer ,Original Research ,Membrane tubulation ,Vesicle ,Bilayer ,molecular dynamic ,Lipid bilayer fusion ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Chemistry ,medicine.anatomical_structure ,Membrane ,lcsh:QD1-999 ,chemistry ,Biophysics ,0210 nano-technology - Abstract
Gp36 is the virus envelope glycoproteins catalyzing the fusion of the feline immunodeficiency virus with the host cells. The peptide C8 is a tryptophan-rich peptide corresponding to the fragment 770W-I777 of gp36 exerting antiviral activity by binding the membrane cell and inhibiting the virus entry. Several factors, including the membrane surface charge, regulate the binding of C8 to the lipid membrane. Based on the evidence that imperceptible variation of membrane charge may induce a dramatic effect in several critical biological events, in the present work we investigate the effect induced by systematic variation of charge in phospholipid bilayers on the aptitude of C8 to interact with lipid membranes, the tendency of C8 to assume specific conformational states and the re-organization of the lipid bilayer upon the interaction with C8. Accordingly, employing a bottom-up multiscale protocol, including CD, NMR, ESR spectroscopy, atomistic molecular dynamics simulations, and confocal microscopy, we studied C8 in six membrane models composed of different ratios of zwitterionic/negatively charged phospholipids. Our data show that charge content modulates C8-membrane binding with significant effects on the peptide conformations. C8 in micelle solution or in SUV formed by DPC or DOPC zwitterionic phospholipids assumes regular β-turn structures that are progressively destabilized as the concentration of negatively charged SDS or DOPG phospholipids exceed 40%. Interaction of C8 with zwitterionic membrane surface is mediated by Trp1 and Trp4 that are deepened in the membrane, forming H-bonds and cation-π interactions with the DOPC polar heads. Additional stabilizing salt bridge interactions involve Glu2 and Asp3. MD and ESR data show that the C8-membrane affinity increases as the concentration of zwitterionic phospholipid increases. In the lipid membrane characterized by an excess of zwitterionic phospholipids, C8 is adsorbed at the membrane interface, inducing a stiffening of the outer region of the DOPC bilayer. However, the bound of C8 significantly perturbs the whole organization of lipid bilayer resulting in membrane remodeling. These events, measurable as a variation of the bilayer thickness, are the onset mechanism of the membrane fusion and vesicle tubulation observed in confocal microscopy by imaging zwitterionic MLVs in the presence of C8 peptide.
- Published
- 2020
24. Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis
- Author
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Giorgio Della Sala, Rafael Cano, Vito Capaccio, Marina Sicignano, José Alemán, Luca Bernardi, Francesco De Riccardis, Sergio Díaz-Tendero, Ricardo I. Rodríguez, Fabio Borello, UAM. Departamento de Química, UAM. Departamento de Química Orgánica, Sicignano M., Rodriguez R.I., Capaccio V., Borello F., Cano R., De Riccardis F., Bernardi L., Diaz-Tendero S., Della Sala G., and Aleman J.
- Subjects
Chemistry ,Organic Chemistry ,Enantioselective synthesis ,Quinidinium ,Chiral phase ,Química ,Azlactone ,Biochemistry ,Electron ,Catalysis ,Phase-Transfer Catalysi ,Transfer (group theory) ,Computational chemistry ,Phase (matter) ,Trifluormethylthiolation ,Asymmetric synthesi ,Physical and Theoretical Chemistry ,Aryl groups - Abstract
The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculations, We are grateful to the Spanish Government (RTI2018-095038-B-I00, CTQ, CTQ2016-76061-P), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367)
- Published
- 2020
25. Tuning the biomimetic performances of 4-hydroxyproline-containing cyclic peptoids
- Author
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Paolo Tecilla, Irene Izzo, Ines Bruno, J. Buirey, F. De Riccardis, G. Della Sala, Massimo Tosolini, Mariacarmela Vaccaro, Rosaria Schettini, Chiara Costabile, Schettini, R., Costabile, C., Della Sala, G., Buirey, J., Tosolini, M., Tecilla, P., Vaccaro, M. C., Bruno, I., De Riccardis, F., and Izzo, I.
- Subjects
Supramolecular chemistry ,cyclic peptoid ,ion transport ,Antineoplastic Agents ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Peptoids ,Hydroxyproline ,chemistry.chemical_compound ,Biomimetic Materials ,Cell Line, Tumor ,Humans ,Physical and Theoretical Chemistry ,Ion transporter ,Cell Proliferation ,Liposome ,010405 organic chemistry ,Sodium ,Organic Chemistry ,Alkali metal ,Combinatorial chemistry ,Affinities ,0104 chemical sciences ,Monomer ,chemistry ,Surface modification - Abstract
Five new cyclic peptoids containing (2S,4R)-4-hydroxyproline (Hyp) residues have been designed and synthesized using a mixed "submonomer/monomer" approach. Alkali metal cation affinities and ion transport activities were assessed by experimental (NMR and HPTS assay in liposomes) and computational methods. Easy functionalization of hydroxyproline residues afforded a bouquet of cyclic oligomers showing correlation between ion transport abilities and cytotoxic activities on selected human cancer cell lines.
- Published
- 2018
26. Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update
- Author
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Carmela Mazzoccoli, Gerardo Della Sala, Valeria Costantino, Tiziana Tataranni, Claudia Piccoli, Francesca Agriesti, Della Sala, G., Agriesti, F., Mazzoccoli, C., Tataranni, T., Costantino, V., and Piccoli
- Subjects
0301 basic medicine ,natural product ,Aquatic Organisms ,Proteasome Endopeptidase Complex ,natural products ,Pharmaceutical Science ,Antineoplastic Agents ,secondary metabolite ,Review ,Biology ,Protein degradation ,high-throughput screening ,03 medical and health sciences ,chemistry.chemical_compound ,Ubiquitin ,Drug Development ,Neoplasms ,Drug Discovery ,ubiquitin ,medicine ,lead compounds ,Animals ,Humans ,cancer ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,lcsh:QH301-705.5 ,Biological Products ,Natural product ,Bortezomib ,secondary metabolites ,Ubiquitin-Protein Ligase Complexes ,marine ,Invertebrates ,Cell biology ,030104 developmental biology ,proteasome ,Proteasome ,chemistry ,lcsh:Biology (General) ,Cancer cell ,Proteolysis ,Proteasome inhibitor ,biology.protein ,salinosporamide ,Salinosporamide A ,Proteasome Inhibitors ,medicine.drug ,Signal Transduction - Abstract
The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory and misfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites targeting the UPP. These chemically intriguing compounds can inspire clinical development of novel antitumor drugs to cope with the incessant outbreak of side effects and resistance mechanisms induced by currently approved proteasome inhibitors (e.g., bortezomib). In this review, we report about (a) the role of the UPP in anticancer therapy, (b) chemical and biological properties of UPP inhibitors from marine sources discovered in the last decade, (c) high-throughput screening techniques for mining natural UPP inhibitors in organic extracts. Moreover, we will tell about the fascinating story of salinosporamide A, the first marine natural product to access clinical trials as a proteasome inhibitor for cancer treatment.
- Published
- 2018
27. Synthesis and complexing properties of cyclic benzylopeptoids-a new family of extended macrocyclic peptoids
- Author
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Massimo Tosolini, G. Della Sala, Stefania Gambaro, F. De Riccardis, Chiara Costabile, Irene Izzo, Alessandra Meli, Domenico Milano, Paolo Tecilla, Carmen Talotta, Meli, A., Gambaro, S., Costabile, C., Talotta, C., Della Sala, G., Tecilla, Paolo, Milano, D., Tosolini, Massimo, Izzo, I., and De Riccardis, F.
- Subjects
Models, Molecular ,Annulation ,Macrocyclic Compounds ,Stereochemistry ,Supramolecular chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,supramolecular chemistry ,ion transport ,Peptoids ,Benzyl Compounds ,supramolecular chemistry, ion transport, cyclic peptoid ,Physical and Theoretical Chemistry ,Ion transporter ,Ionophores ,010405 organic chemistry ,Chemistry ,Sodium ,Organic Chemistry ,Combinatorial chemistry ,Affinities ,0104 chemical sciences ,cyclic peptoid ,Cyclization - Abstract
An efficient protocol for the solid-phase synthesis of six members of a new class of extended macrocyclic peptoids (based on ortho-, meta- and para-N-(methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3–5) and tetramers (6–8) demonstrate that annulation of the rigidified peptoids can generate new hosts with the ability to sequestrate one or two sodium cations with the affinities and stoichiometries defined by the macrocycle morphology. Ion transport studies have been also performed in order to better appreciate the factors promoting transmembrane cation translocation.
- Published
- 2016
28. Towards the biosynthesis of the aromatic products of the Mediterranean mollusc Scaphander lignarius: isolation and synthesis of analogues of lignarenones
- Author
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Aldo Spinella, Anna Domènech Coll, Guido Cimino, Adele Cutignano, Angelo Fontana, Carmela Della Monica, Giorgio Della Sala, Giuliana d'Ippolito, Gianpiero Calabrese, Della Sala, G., Cutignano, A., Fontana, A, Spinella, A., Calabrese, G., Domenech-Coll, A., D’Ippolito, G., Della Monica, C., and Cimino, G
- Subjects
Mediterranean climate ,biology ,Stereochemistry ,Organic Chemistry ,Enantioselective synthesis ,Biosynthesis ,biology.organism_classification ,Biochemistry ,chemistry.chemical_compound ,Polyketide ,chemistry ,Organic synthesi ,Drug Discovery ,Scaphander lignarius ,Structure Elucidation ,Biological sciences - Abstract
Secondary metabolites of the Mediterranean mollusc Scaphander lignarius from different collection sites have been investigated, proving the constant presence of a number of minor metabolites correlated to the already known lignarenones. Complete characterization of the new metabolites has been supported by enantioselective synthesis. The data are consistent with the origin of this unique class of ω-phenyloctanoids from a common polyketide pathway.
- Published
- 2007
29. 1,2,3-Triazole-Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid-State Studies.
- Author
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Araszczuk AM, Pierri G, Schettini R, Costabile C, Della Sala G, Di Marino L, Tedesco C, De Riccardis F, and Izzo I
- Abstract
Two new chiral 1,2,3-triazole-containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid-phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα-chiral side chains and their conformational attitudes. BH
3 -mediated reduction of the tertiary amide groups of known 1-3 and newly synthesized 4 gave novel azamacrocycles 6-9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X-ray diffraction studies, demonstrated the peculiar properties of 1,2,3-triazole-containing macrorings., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
- Full Text
- View/download PDF
30. When Synthesis Gets It Wrong: Unexpected Epimerization Using PyBOP in the Synthesis of the Cyclic Peptide Thermoactinoamide A.
- Author
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Di Matteo V, Esposito G, Costantino V, Della Sala G, Teta R, and Mangoni A
- Subjects
- Molecular Structure, Cyclization, Biological Products chemistry, Biological Products chemical synthesis, Stereoisomerism, Thermoactinomyces chemistry, Peptides, Cyclic chemistry, Peptides, Cyclic chemical synthesis
- Abstract
Chemical synthesis is commonly seen as the final proof of the structure of complex natural products, but even a seemingly easy and well-established synthetic procedure may lead to an unexpected result. This is what happened with the synthesis of thermoactinoamide A ( 1a ), an antimicrobial and antitumor nonribosomal cyclic hexapeptide produced by the thermophilic bacterium Thermoactinomyces vulgaris . The synthetic thermoactinoamide A outsourced to a company and the one described in a synthetic paper showed spectroscopic data identical to each other but different from those of the natural product. After a detailed spectroscopic, degradative, and synthetic study, the synthetic compound was shown to be an epimer ( 1b ) of the intended target compound, originating during the cyclization reaction by extensive epimerization at the activated C-terminal amino acid. This allowed confirmation of the structure of the natural product.
- Published
- 2024
- Full Text
- View/download PDF
31. Biological evaluation of [4-(4-aminophenyl)-1-(4-fluorophenyl)-1H-pyrrol-3-yl](3,4,5-trimethoxyphenyl)methanone as potential antineoplastic agent in 2D and 3D breast cancer models.
- Author
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Mazzoccoli C, Crispo F, Laurenzana I, Pietrafesa M, Sisinni L, Lerose R, Telesca D, Milella MR, Liu T, Della Sala G, Sebastiani J, Silvestri R, and La Regina G
- Subjects
- Humans, Female, Structure-Activity Relationship, Doxorubicin pharmacology, Cell Proliferation, Adenosine Triphosphate, Cell Line, Tumor, Breast Neoplasms drug therapy, Antineoplastic Agents pharmacology
- Abstract
Targeting tubulin polymerization and depolymerization represents a promising approach to treat solid tumors. In this study, we investigated the molecular mechanisms underlying the anticancer effects of a structurally novel tubulin inhibitor, [4-(4-aminophenyl)-1-(4-fluorophenyl)-1H-pyrrol-3-yl](3,4,5-trimethoxyphenyl)methanone (ARDAP), in two- and three-dimensional MCF-7 breast cancer models. At sub-cytotoxic concentrations, ARDAP showed a marked decrease in cell proliferation, colony formation, and ATP intracellular content in MCF-7 cells, by acting through a cytostatic mechanism. Additionally, drug exposure caused blockage of the epithelial-to-mesenchymal transition (EMT). In 3D cell culture, ARDAP negatively affected tumor spheroid growth, with inhibition of spheroid formation and reduction of ATP concentration levels. Notably, ARDAP exposure promoted the differentiation of MCF-7 cells by inducing: (i) expression decrease of Oct4 and Sox2 stemness markers, both in 2D and 3D models, and (ii) downregulation of the stem cell surface marker CD133 in 2D cell cultures. Interestingly, treated MCF7 cells displayed a major sensitivity to cytotoxic effects of the conventional chemotherapeutic drug doxorubicin. In addition, although exhibiting growth inhibitory effects against breast cancer cells, ARDAP showed insignificant harm to MCF10A healthy cells. Collectively, our results highlight the potential of ARDAP to emerge as a new chemotherapeutic agent or adjuvant compound in chemotherapeutic treatments., (© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
- Published
- 2023
- Full Text
- View/download PDF
32. New Imidazolium Alkaloids with Broad Spectrum of Action from the Marine Bacterium Shewanella aquimarina .
- Author
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Giugliano R, Della Sala G, Buonocore C, Zannella C, Tedesco P, Palma Esposito F, Ragozzino C, Chianese A, Morone MV, Mazzella V, Núñez-Pons L, Folliero V, Franci G, De Filippis A, Galdiero M, and de Pascale D
- Abstract
The continuous outbreak of drug-resistant bacterial and viral infections imposes the need to search for new drug candidates. Natural products from marine bacteria still inspire the design of pharmaceuticals. Indeed, marine bacteria have unique metabolic flexibility to inhabit each ecological niche, thus expanding their biosynthetic ability to assemble unprecedented molecules. The One-Strain-Many-Compounds approach and tandem mass spectrometry allowed the discovery of a Shewanella aquimarina strain as a source of novel imidazolium alkaloids via molecular networking. The alkaloid mixture was shown to exert bioactivities such as: (a) antibacterial activity against antibiotic-resistant Staphylococcus aureus clinical isolates at 100 µg/mL, (b) synergistic effects with tigecycline and linezolid, (c) restoration of MRSA sensitivity to fosfomycin, and (d) interference with the biofilm formation of S. aureus 6538 and MRSA. Moreover, the mixture showed antiviral activity against viruses with and without envelopes. Indeed, it inhibited the entry of coronavirus HcoV-229E and herpes simplex viruses into human cells and inactivated poliovirus PV-1 in post-infection assay at 200 µg/mL. Finally, at the same concentration, the fraction showed anthelminthic activity against Caenorhabditis elegans , causing 99% mortality after 48 h. The broad-spectrum activities of these compounds are partially due to their biosurfactant behavior and make them promising candidates for breaking down drug-resistant infectious diseases.
- Published
- 2023
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33. A metabologenomics approach to unlock the metabolome of the novel Antarctic deep-sea isolate Lacinutrix shetlandiensis sp. nov. WUR7.
- Author
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Vitale GA, January GG, Oppong-Danquah E, Della Sala G, Palma Esposito F, Tasdemir D, and de Pascale D
- Abstract
The South Shetland Trough, Antarctica, is an underexplored region for microbiological and biotechnological exploitation. Herein, we describe the isolation and characterization of the novel bacterium Lacinutrix shetlandiensis sp. nov. WUR7 from a deep-sea environment. We explored its chemical diversity via a metabologenomics approach, wherein the OSMAC strategy was strategically employed to upregulate cryptic genes for secondary metabolite production. Based on hybrid de novo whole genome sequencing and digital DNA-DNA hybridization, isolate WUR7 was identified as a novel species from the Gram-negative genus Lacinutrix . Its genome was mined for the presence of biosynthetic gene clusters with limited results. However, extensive investigation of its metabolism uncovered an unusual tryptophan decarboxylase with high sequence homology and conserved structure of the active site as compared to ZP_02040762, a highly specific tryptophan decarboxylase from Ruminococcus gnavus . Therefore, WUR7's metabolism was directed toward indole-based alkaloid biosynthesis by feeding it with L -tryptophan. As expected, its metabolome profile changed dramatically, by triggering the extracellular accumulation of a massive array of metabolites unexpressed in the absence of tryptophan. Untargeted LC-MS/MS coupled with molecular networking, followed along with chemoinformatic dereplication, allowed for the annotation of 10 indole alkaloids, belonging to β-carboline, bisindole, and monoindole classes, alongside several unknown alkaloids. These findings guided us to the isolation of a new natural bisindole alkaloid 8,9-dihydrocoscinamide B ( 1 ), as the first alkaloid from the genus Lacinutrix , whose structure was elucidated on the basis of extensive 1D and 2D NMR and HR-ESIMS experiments. This comprehensive strategy allowed us to unlock the previously unexploited metabolome of L. shetlandiensis sp. nov. WUR7., Competing Interests: The authors declare no conflict of interest, (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)
- Published
- 2023
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34. Water-Soluble Chiral Cyclic Peptoids and Their Sodium and Gadolinium Complexes: Study of Conformational and Relaxometric Properties.
- Author
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D'Amato A, Jiang L, Della Sala G, Kirshenbaum K, Costabile C, Furlan C, Gianolio E, Izzo I, and De Riccardis F
- Abstract
Cyclic peptoids are macrocyclic oligomers of N-substituted glycines with specific folding abilities and excellent metal binding properties. In this work, we show how strategic positioning of chiral ( S )- and ( R )-(1-carboxyethyl)glycine units influences the conformational stability of water-soluble macrocyclic peptoids as sodium complexes. The reported results are based on nuclear magnetic resonance spectroscopy, extensive computational studies, and X-ray diffraction analysis using single crystals grown from aqueous solutions. The studies include
1 H relaxometric investigations of hexameric cyclic peptoids in the presence of the Gd3+ ion to assess their thermodynamic stabilities and relaxivities.- Published
- 2023
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35. Enhanced Molecular Networking Shows Microbacterium sp. V1 as a Factory of Antioxidant Proline-Rich Peptides.
- Author
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Vitale GA, Scarpato S, Mangoni A, D'Auria MV, Della Sala G, and de Pascale D
- Subjects
- Animals, Microbacterium, Proline, Tandem Mass Spectrometry, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Peptides, Bacteria, Antioxidants, Peptides, Cyclic chemistry
- Abstract
Two linear proline-rich peptides ( 1 - 2 ), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium Microbacterium sp. V1, associated with the marine sponge Petrosia ficiformis , collected in the volcanic CO
2 vents in Ischia Island (South Italy). Peptide production was triggered at low temperature following the one strain many compounds (OSMAC) method. Both peptides were detected together with other peptides ( 3 - 8 ) via an integrated, untargeted MS/MS-based molecular networking and cheminformatic approach. The planar structure of the peptides was determined by extensive 1D and 2D NMR and HR-MS analysis, and the stereochemistry of the aminoacyl residues was inferred by Marfey's analysis. Peptides 1 - 8 are likely to arise from Microbacterium V1 tailor-made proteolysis of tryptone. Peptides 1 and 2 were shown to display antioxidant properties in the ferric-reducing antioxidant power (FRAP) assay.- Published
- 2023
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36. Evaluation of Antimicrobial Properties and Potential Applications of Pseudomonas gessardii M15 Rhamnolipids towards Multiresistant Staphylococcus aureus .
- Author
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Buonocore C, Giugliano R, Della Sala G, Palma Esposito F, Tedesco P, Folliero V, Galdiero M, Franci G, and de Pascale D
- Abstract
Staphylococcus aureus is a Gram-positive opportunistic human pathogen responsible for severe infections and thousands of deaths annually, mostly due to its multidrug-resistant (MDR) variants. The cell membrane has emerged as a promising new therapeutic target, and lipophilic molecules, such as biosurfactants, are currently being utilized. Herein, we evaluated the antimicrobial activity of a rhamnolipids mixture produced by the Antarctic marine bacterium Pseudomonas gessardii M15. We demonstrated that our mixture has bactericidal activity in the range of 12.5-50 µg/mL against a panel of clinical MDR isolates of S. aureus , and that the mixture eradicated the bacterial population in 30 min at MIC value, and in 5 min after doubling the concentration. We also tested abilities of RLs to interfere with biofilm at different stages and determined that RLs can penetrate biofilm and kill the bacteria at sub-MICs values. The mixture was then used to functionalize a cotton swab to evaluate the prevention of S. aureus proliferation. We showed that by using 8 µg of rhamnolipids per swab, the entire bacterial load is eradicated, and just 0.5 µg is sufficient to reduce the growth by 99.99%. Our results strongly indicate the possibility of using this mixture as an additive for wound dressings for chronic wounds.
- Published
- 2023
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37. Macrocyclic Triazolopeptoids: A Promising Class of Extended Cyclic Peptoids.
- Author
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Araszczuk AM, D'Amato A, Schettini R, Costabile C, Della Sala G, Pierri G, Tedesco C, De Riccardis F, and Izzo I
- Subjects
- Models, Molecular, Molecular Conformation, Cyclization, Peptoids chemistry
- Abstract
Head-to-tail cyclization of linear oligoamides containing 4-benzylaminomethyl-1 H -1,2,3-triazol-1-yl acetic acid monomers afforded a novel class of "extended macrocyclic peptoids". The identification of the conformation in solution for a cyclodimer and the X-ray crystal structure of a cyclic tetraamide are reported.
- Published
- 2022
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38. Novel Insights on Pyoverdine: From Biosynthesis to Biotechnological Application.
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Dell'Anno F, Vitale GA, Buonocore C, Vitale L, Palma Esposito F, Coppola D, Della Sala G, Tedesco P, and de Pascale D
- Subjects
- Iron metabolism, Pseudomonas metabolism, Pseudomonas aeruginosa metabolism, Oligopeptides metabolism, Siderophores metabolism
- Abstract
Pyoverdines (PVDs) are a class of siderophores produced mostly by members of the genus Pseudomonas . Their primary function is to accumulate, mobilize, and transport iron necessary for cell metabolism. Moreover, PVDs also play a crucial role in microbes' survival by mediating biofilm formation and virulence. In this review, we reorganize the information produced in recent years regarding PVDs biosynthesis and pathogenic mechanisms, since PVDs are extremely valuable compounds. Additionally, we summarize the therapeutic applications deriving from the PVDs' use and focus on their role as therapeutic target themselves. We assess the current biotechnological applications of different sectors and evaluate the state-of-the-art technology relating to the use of synthetic biology tools for pathway engineering. Finally, we review the most recent methods and techniques capable of identifying such molecules in complex matrices for drug-discovery purposes.
- Published
- 2022
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39. Mixotrophy in a Local Strain of Nannochloropsis granulata for Renewable High-Value Biomass Production on the West Coast of Sweden
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Villanova V, Galasso C, Vitale GA, Della Sala G, Engelbrektsson J, Strömberg N, Shaikh KM, Andersson MX, Palma Esposito F, Ekendahl S, De Pascale D, and Spetea C
- Subjects
- Biomass, Carbon Dioxide metabolism, Carotenoids metabolism, Glycerol, Humans, Sweden, Microalgae metabolism, Stramenopiles metabolism
- Abstract
A local strain of Nannochloropsis granulata ( Ng ) has been reported as the most productive microalgal strain in terms of both biomass yield and lipid content when cultivated in photobioreactors that simulate the light and temperature conditions during the summer on the west coast of Sweden. To further increase the biomass and the biotechnological potential of this strain in these conditions, mixotrophic growth (i.e., the simultaneous use of photosynthesis and respiration) with glycerol as an external carbon source was investigated in this study and compared with phototrophic growth that made use of air enriched with 1-2% CO
2 . The addition of either glycerol or CO2 -enriched air stimulated the growth of Ng and theproduction of high-value long-chain polyunsaturated fatty acids (EPA) as well as the carotenoid canthaxanthin. Bioassays in human prostate cell lines indicated the highest antitumoral activity for Ng extracts and fractions from mixotrophic conditions. Metabolomics detected betaine lipids specifically in the bioactive fractions, suggesting their involvement in the observed antitumoral effect. Genes related to autophagy were found to be upregulated by the most bioactive fraction, suggesting a possible therapeutic target against prostate cancer progression. Taken together, our results suggest that the local Ng strain can be cultivated mixotrophically in summer conditions on the west coast of Sweden for the production of high-value biomass containing antiproliferative compounds, carotenoids, and EPA.- Published
- 2022
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40. Unveiling Metabolic Vulnerability and Plasticity of Human Osteosarcoma Stem and Differentiated Cells to Improve Cancer Therapy.
- Author
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Della Sala G, Pacelli C, Agriesti F, Laurenzana I, Tucci F, Tamma M, Capitanio N, and Piccoli C
- Abstract
Defining the metabolic phenotypes of cancer-initiating cells or cancer stem cells and of their differentiated counterparts might provide fundamental knowledge for improving or developing more effective therapies. In this context we extensively characterized the metabolic profiles of two osteosarcoma-derived cell lines, the 3AB-OS cancer stem cells and the parental MG-63 cells. To this aim Seahorse methodology-based metabolic flux analysis under a variety of conditions complemented with real time monitoring of cell growth by impedentiometric technique and confocal imaging were carried out. The results attained by selective substrate deprivation or metabolic pathway inhibition clearly show reliance of 3AB-OS on glycolysis and of MG-63 on glutamine oxidation. Treatment of the osteosarcoma cell lines with cisplatin resulted in additive inhibitory effects in MG-63 cells depleted of glutamine whereas it antagonized under selective withdrawal of glucose in 3AB-OS cells thereby manifesting a paradoxical pro-survival, cell-cycle arrest in S phase and antioxidant outcome. All together the results of this study highlight that the efficacy of specific metabolite starvation combined with chemotherapeutic drugs depends on the cancer compartment and suggest cautions in using it as a generalizable curative strategy.
- Published
- 2021
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41. Structural dynamism of chiral sodium peraza-macrocycle complexes derived from cyclic peptoids.
- Author
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Schettini R, D'Amato A, Araszczuk AM, Della Sala G, Costabile C, D'Ursi AM, Grimaldi M, Izzo I, and De Riccardis F
- Subjects
- Density Functional Theory, Stereoisomerism, Coordination Complexes chemistry, Coordination Complexes chemical synthesis, Aza Compounds chemistry, Aza Compounds chemical synthesis, Macrocyclic Compounds chemistry, Macrocyclic Compounds chemical synthesis, Peptides, Cyclic chemistry, Peptides, Cyclic chemical synthesis, Molecular Structure, Molecular Conformation, Models, Molecular, Peptoids chemistry, Peptoids chemical synthesis, Sodium chemistry
- Abstract
A variety of cyclen and hexacyclen derivatives decorated with (S)-1-phenylethyl side chains or (S)-pyrrolidine units have been prepared via a reductive approach from the corresponding cyclic peptoids containing N-(S)-(1-phenylethyl)glycine and l-proline residues. Spectroscopic and DFT studies on their Na
+ complexes show that point chirality and ring size play a crucial role in controlling the structural dynamism of 1,2-diaminoethylene units and pendant arms. The detection of highly symmetric C4 - and C3 -symmetric metalated species demonstrates that a full understanding of the relationship between the structure and conformational properties of peraza-macrocyclic metal complexes is possible.- Published
- 2021
- Full Text
- View/download PDF
42. Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus .
- Author
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Palma Esposito F, Giugliano R, Della Sala G, Vitale GA, Buonocore C, Ausuri J, Galasso C, Coppola D, Franci G, Galdiero M, and de Pascale D
- Subjects
- Animals, Antiviral Agents analysis, Chlorocebus aethiops, Culture Techniques, Drug Screening Assays, Antitumor, Esters metabolism, Genome, Bacterial, Glycolipids chemistry, Humans, Metabolome, Microbial Sensitivity Tests, Molecular Structure, PC-3 Cells, Rhodococcus chemistry, Rhodococcus genetics, Succinates metabolism, Surface-Active Agents chemistry, Surface-Active Agents metabolism, Vero Cells, Antiviral Agents metabolism, Glycolipids metabolism, Rhodococcus metabolism
- Abstract
Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.
- Published
- 2021
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- View/download PDF
43. Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolo-Pyrimidinones Tethered with Hydrazide-Hydrazones.
- Author
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Horchani M, Della Sala G, Caso A, D'Aria F, Esposito G, Laurenzana I, Giancola C, Costantino V, Jannet HB, and Romdhane A
- Subjects
- Antineoplastic Agents, Drug Screening Assays, Antitumor, ErbB Receptors antagonists & inhibitors, ErbB Receptors chemistry, ErbB Receptors metabolism, Female, Humans, MCF-7 Cells, Apoptosis drug effects, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Proliferation drug effects, G-Quadruplexes, Molecular Docking Simulation, Proto-Oncogene Proteins p21(ras) antagonists & inhibitors, Proto-Oncogene Proteins p21(ras) chemistry, Proto-Oncogene Proteins p21(ras) metabolism, Pyrimidinones chemical synthesis, Pyrimidinones chemistry, Pyrimidinones pharmacology
- Abstract
Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4- d ]pyrimidin-4( 5H )-ones tethered with hydrazide-hydrazones, 5a - h , was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a , 5e , 5g , and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a , 5e , 5g , and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a , 5e , 5g , and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.
- Published
- 2021
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44. New Tricks with an Old Sponge: Feature-Based Molecular Networking Led to Fast Identification of New Stylissamide L from Stylissa caribica .
- Author
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Scarpato S, Teta R, Della Sala G, Pawlik JR, Costantino V, and Mangoni A
- Subjects
- Animals, Cell Movement drug effects, Cell Proliferation drug effects, Humans, MCF-7 Cells, Metabolomics, Molecular Structure, Neoplasms drug therapy, Neoplasms pathology, Peptides, Cyclic isolation & purification, Peptides, Cyclic metabolism, Secondary Metabolism, Structure-Activity Relationship, Peptides, Cyclic pharmacology, Porifera metabolism
- Abstract
Feature-based molecular networking was used to re-examine the secondary metabolites in extracts of a very well studied marine sponge, Stylissa caribica , known to contain a large array of cyclic peptides and brominated alkaloids. The analysis revealed the presence of 13 cyclic peptides in the sponge that had never been detected in previous work and appeared to be new compounds. The most abundant one was isolated and shown to be a new proline-rich cyclic heptapetide that was called stylissamide L ( 1 ). Structure of compound 1 , including the cis/trans geometry of the three proline residues, was determined by extensive NMR studies; the l configuration of the seven amino acid residues was determined using Marfey's method. Stylissamide L was tested for activity as a cell growth inhibitor and cell migration inhibitor on two cancer cell lines but, unlike other members of the stylissamide family, it showed no significant activity. This approach showed that even a thoroughly studied species such as S. caribica may contain new chemistry that can be revealed if studied with the right tools.
- Published
- 2020
- Full Text
- View/download PDF
45. Binding of the Anti-FIV Peptide C8 to Differently Charged Membrane Models: From First Docking to Membrane Tubulation.
- Author
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Di Marino D, Bruno A, Grimaldi M, Scrima M, Stillitano I, Amodio G, Della Sala G, Romagnoli A, De Santis A, Moltedo O, Remondelli P, Boccia G, D'Errico G, D'Ursi AM, and Limongelli V
- Abstract
Gp36 is the virus envelope glycoproteins catalyzing the fusion of the feline immunodeficiency virus with the host cells. The peptide C8 is a tryptophan-rich peptide corresponding to the fragment
770 W-I777 of gp36 exerting antiviral activity by binding the membrane cell and inhibiting the virus entry. Several factors, including the membrane surface charge, regulate the binding of C8 to the lipid membrane. Based on the evidence that imperceptible variation of membrane charge may induce a dramatic effect in several critical biological events, in the present work we investigate the effect induced by systematic variation of charge in phospholipid bilayers on the aptitude of C8 to interact with lipid membranes, the tendency of C8 to assume specific conformational states and the re-organization of the lipid bilayer upon the interaction with C8. Accordingly, employing a bottom-up multiscale protocol, including CD, NMR, ESR spectroscopy, atomistic molecular dynamics simulations, and confocal microscopy, we studied C8 in six membrane models composed of different ratios of zwitterionic/negatively charged phospholipids. Our data show that charge content modulates C8-membrane binding with significant effects on the peptide conformations. C8 in micelle solution or in SUV formed by DPC or DOPC zwitterionic phospholipids assumes regular β-turn structures that are progressively destabilized as the concentration of negatively charged SDS or DOPG phospholipids exceed 40%. Interaction of C8 with zwitterionic membrane surface is mediated by Trp1 and Trp4 that are deepened in the membrane, forming H-bonds and cation-π interactions with the DOPC polar heads. Additional stabilizing salt bridge interactions involve Glu2 and Asp3. MD and ESR data show that the C8-membrane affinity increases as the concentration of zwitterionic phospholipid increases. In the lipid membrane characterized by an excess of zwitterionic phospholipids, C8 is adsorbed at the membrane interface, inducing a stiffening of the outer region of the DOPC bilayer. However, the bound of C8 significantly perturbs the whole organization of lipid bilayer resulting in membrane remodeling. These events, measurable as a variation of the bilayer thickness, are the onset mechanism of the membrane fusion and vesicle tubulation observed in confocal microscopy by imaging zwitterionic MLVs in the presence of C8 peptide., (Copyright © 2020 Di Marino, Bruno, Grimaldi, Scrima, Stillitano, Amodio, Della Sala, Romagnoli, De Santis, Moltedo, Remondelli, Boccia, D'Errico, D'Ursi and Limongelli.)- Published
- 2020
- Full Text
- View/download PDF
46. Identification of the Biosynthetic Gene Cluster of Thermoactinoamides and Discovery of New Congeners by Integrated Genome Mining and MS-Based Molecular Networking.
- Author
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Della Sala G, Mangoni A, Costantino V, and Teta R
- Abstract
The putative non-ribosomal peptide synthetase (NRPS) gene cluster encoding the biosynthesis of the bioactive cyclohexapeptide thermoactinoamide A ( 1 ) was identified in Thermoactinomyces vulgaris DSM 43016. Based on an in silico prediction, the biosynthetic operon was shown to contain two trimodular NRPSs, designated as ThdA and ThdB, respectively. Chemical analysis of a bacterial crude extract showed the presence of thermoactinoamide A ( 1 ), thereby supporting this biosynthetic hypothesis. Notably, integrating genome mining with a LC-HRMS/MS molecular networking-based investigation of the microbial metabolome, we succeeded in the identification of 10 structural variants ( 2-11 ) of thermoactinoamide A ( 1 ), five of them being new compounds (thermoactinoamides G-K, 7 - 11 ). As only one thermoactinoamide operon was found in T. vulgaris , it can be assumed that all thermoactinoamide congeners are assembled by the same multimodular NRPS system. In light of these findings, we suggest that the thermoactinoamide synthetase is able to create chemical diversity, combining the relaxed substrate selectivity of some adenylation domains with the iterative and/or alternative use of specific modules. In the frame of our screening program to discover antitumor natural products, thermoactinoamide A ( 1 ) was shown to exert a moderate growth-inhibitory effect in BxPC-3 cancer cells in the low micromolar range, while being inactive in PANC-1 and 3AB-OS solid tumor models., (Copyright © 2020 Della Sala, Mangoni, Costantino and Teta.)
- Published
- 2020
- Full Text
- View/download PDF
47. Peptoid-based siderophore mimics as dinuclear Fe 3+ chelators.
- Author
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D'Amato A, Ghosh P, Costabile C, Della Sala G, Izzo I, Maayan G, and De Riccardis F
- Subjects
- Chelating Agents chemical synthesis, Cyclization, Models, Molecular, Molecular Conformation, Peptoids chemical synthesis, Chelating Agents chemistry, Ferric Compounds chemistry, Peptoids chemistry
- Abstract
A practical synthesis of preorganized tripodal enterobactin/corynebactin-type ligands (consisting of a C
3 -symmetric macrocyclic peptoid core, three catecholamide coordinating units, and C2 , C4 , and C6 spacers) is reported. The formation of complexes with Fe3+ was investigated by spectrophotometric (UV-Vis) and spectrometric (ESI, negative ionization mode) methods and corroborated by theoretical (DFT) calculations. Preliminary studies revealed the intricate interplay between the conformational chirality of cyclic trimeric peptoids and metal coordination geometry of mononuclear species similar to that of natural catechol-based siderophores. Experimental results demonstrated the unexpected formation of unique dinuclear Fe3+ complexes.- Published
- 2020
- Full Text
- View/download PDF
48. Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis.
- Author
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Sicignano M, Rodríguez RI, Capaccio V, Borello F, Cano R, De Riccardis F, Bernardi L, Díaz-Tendero S, Della Sala G, and Alemán J
- Abstract
The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculations.
- Published
- 2020
- Full Text
- View/download PDF
49. Asymmetric Synthesis of α-Trifluoromethylthio-β-Amino Acids under Phase Transfer Catalysis.
- Author
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Capaccio V, Sicignano M, Rodríguez RI, Della Sala G, and Alemán J
- Abstract
The first asymmetric α-trifluoromethylthiolation of 2-substituted isoxazolidin-5-ones was developed using Maruoka type N -spiro ammonium catalysts under phase-transfer conditions. The resulting products, containing a trifluoromethylthiolated quaternary chiral carbon, were obtained in moderate to good yields and up to 98:2 enantiomeric ratio. Moreover, the easy N-O bond cleavage provided access to undescribed α-trifluoromethylthio-β
2,2 -amino acids, with promising applications in biochemistry and medicinal chemistry.- Published
- 2020
- Full Text
- View/download PDF
50. The Borel map in locally integrable structures.
- Author
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Della Sala G, Cordaro PD, and Lamel B
- Abstract
Given a locally integrable structure V over a smooth manifold Ω and given p ∈ Ω we define the Borel map of V at p as the map which assigns to the germ of a smooth solution of V at p . In this work we continue the study initiated in Barostichi et al. (Math. Nachr. 286(14-15):1439-1451, 2013), Della Sala and Lamel (Int J Math 24(11):1350091, 2013) and present new results regarding the Borel map. We prove a general necessary condition for the surjectivity of the Borel map to hold and also, after developing some new devices, we study some classes of CR structures for which its surjectivity is valid. In the final sections we show how the Borel map can be applied to the study of the algebra of germs of solutions of V at p . In this work we continue the study initiated in Barostichi et al. (Math. Nachr. 286(14-15):1439-1451, 2013), Della Sala and Lamel (Int J Math 24(11):1350091, 2013) and present new results regarding the Borel map. We prove a general necessary condition for the surjectivity of the Borel map to hold and also, after developing some new devices, we study some classes of CR structures for which its surjectivity is valid. In the final sections we show how the Borel map can be applied to the study of the algebra of germs of solutions of V at p ., (© The Author(s) 2019.)
- Published
- 2020
- Full Text
- View/download PDF
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