Papers by Stefania Lamponi
Pharmaceutics
An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic a... more An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields.
Carbohydrate Polymers, 2021
The present paper describes the functionalization of sodium hyaluronate (NaHA) with a small molec... more The present paper describes the functionalization of sodium hyaluronate (NaHA) with a small molecule (2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide) (MMPI) having proven inhibitory activity against membrane metalloproteins involved in inflammatory processes (i.e. MMP12). The obtained derivative (HA-MMPI) demonstrated an increased resistance to the in-vitro degradation by hyaluronidase, viscoelastic properties close to those of healthy human synovial fluid, cytocompatibility towards human chondrocytes and nanomolar affinity towards MMP 12. Thus, HA-MMPI can be considered a good candidate as viscosupplement in the treatment of knee osteoarticular disease.
ACS Chemical Neuroscience, 2021
r gi, Gi a nl u c a, La m p o ni, S t ef a ni a, Valoti, M a s si m o, Go r elli, B e a t ric e, ... more r gi, Gi a nl u c a, La m p o ni, S t ef a ni a, Valoti, M a s si m o, Go r elli, B e a t ric e, S a p o n a r a , Si m o n a , B e n e d u si, M a s ci a, P e c o r elli, Ale s s a n d r a , Mi n e t ti, P a t rizi a, Vala c c hi, Giu s e p p e , Bu ti ni, S t ef a ni a, C a m pi a ni, Gi u s e p p e , G e m m a , S a n d r a , M a c c a r r o n e , M a u r o a n d Di Giov a n ni, Gi u s e p p e 2 0 2 1. S el e c tiv e fa t ty a ci d a mi d e h y d r ol a s e in hi bi to r s a s p o t e n ti al n ov el a n ti e pil e p ti c a g e n t s. ACS C h e mi c al N e u r o s ci e n c e 1 2 (9) , p. 1 7 1 6.
European Journal of Medicinal Chemistry, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Materials Science and Engineering: C, 2019
In this paper we report about the preparation, physicochemical and biological characterization of... more In this paper we report about the preparation, physicochemical and biological characterization of a magneto responsive nanostructured material based on magnetite nanoparticles (NP) coated with hyaluronic acid (HA). A synthetic approach, based on a Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition "click" reaction between azido-functionalized magnetite NP and a derivative of hyaluronic acid bearing propargylated ferulic acid groups (HA-FA-Pg), was developed to link covalently the polymer layer to the magnetite NP. The functionalization steps of the magnetite NP and their coating with the HA-FA-Pg layer were monitored by Fourier Transform Infrared (FTIR) spectroscopy and Thermal Gravimetric Analysis (TGA) while Dynamic Light Scattering (DLS) and ζpotential measurements were performed to characterize the aqueous dispersions of the HA-coated magnetite NP. Aggregation and sedimentation processes were investigated also by UV-visible spectroscopy and the dispersions of HA-coated magnetite NP were found significantly more stable than those of bare NP. Magnetization and zero field cooled/field cooled curves revealed that both bare and HA-coated magnetite NP are superparamagnetic at room temperature. Moreover, cytotoxicity studies showed that the coating with HA-FA-Pg significantly reduces the cytotoxicity of the magnetite NP providing the rational basis for the application of the HA-coated magnetite NP as healthcare material.
Carbohydrate Polymers, 2019
Viscosupplementation, i.e. intra-articular injection of hyaluronic acid derivatives, is considere... more Viscosupplementation, i.e. intra-articular injection of hyaluronic acid derivatives, is considered as the most effective treatment for patients with mild to moderate osteoarthritis. Even if hyaluronic acid is still considered as the gold standard, research is now focusing on the development of new products with enhanced injectability and yet reasonable viscoelastic behavior for OA treatment. A Gellan Gum (GG) hydrogel was synthesized and coated with crosslinked polyvinyl alcohol (PVA) to protect the polysaccharide from degradation during sterilization and improve its performance for the foreseen application. Thermal analyses indicated that mixed hydrogel showed a higher degree of structuring than the bare polysaccharide core without losing its swelling properties, thanks to the hydrophylicity of both coating and cross-linking agent. The PVA coating increased elastic and viscous moduli of the polysaccharide core conferring it a higher resistance to shear and compression and better thixotropic properties. Despite the double crosslinking, hydrogel was injectable. Cytocompatibility towards chondrocytes was verified.
Biophysical Chemistry, 2019
Tyrosol, hydroxytyrosol and oleuropein are among the major phenolic compounds in fruits, leaves a... more Tyrosol, hydroxytyrosol and oleuropein are among the major phenolic compounds in fruits, leaves and oils from Olea europaea L. These natural antioxidants molecules revealed several beneficial effects on human health, but a low bioavailability and accessibility to targeted site. Liposomes are drug/nutraceutical delivery carriers, used for driving bioactive molecules to desired target tissues, decreasing potential side effects and protecting the encapsulated molecule from enzymatic metabolic processes. In this study, zwitterionic liposomes containing tyrosol, hydroxytyrosol and oleuropein were synthesized and characterized for their size and surface charge. Particular attention was devoted to the determination of encapsulation efficiency (EE%), quantifying the loaded Tyr, HTyr and Ole amount, by using three different techniques: direct UV spectrophotometry, High Performance Liquid Chromatography and Trolox Equivalent Antioxidant Capacity assay. The results revealed higher EE% for oleuropein. Cyto-toxicity and cyto-compatibility of liposomes were also tested on human chondrocyte cells.
Future Medicinal Chemistry, 2016
Aim: Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins invol... more Aim: Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in the initiation and progression of cancer. Currently, three hydroxamate-containing HDAC pan-inhibitors have been approved as antitumor agents. Results: We herein present the development of a series of novel phenylpyrrole-based derivatives stemmed from combined computational and medicinal chemistry efforts to rationally modulate HDAC1/6 isoform selectivity. In vitro activity on HDAC1 and HDAC6 isoforms and the effects of selected analogs on histone H3 and α-tubulin acetylation levels were determined. Cell-based data evidenced, for selected compounds, a promising antitumor potential and low toxicity on normal cells. Conclusion: The newly developed compounds represent a valuable starting point for the development of novel anticancer agents.
MedChemComm, 2015
Design, synthesis and molecular docking calculation studies led to the identification of novel sp... more Design, synthesis and molecular docking calculation studies led to the identification of novel spirocyclic peroxides with in vitro and in vivo antimalarial activity.
CNS Neuroscience & Therapeutics, 2014
Aims: We recently described multifunctional tools (2a-c) as potent inhibitors of human Cholineste... more Aims: We recently described multifunctional tools (2a-c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with Ab aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level. Methods: We determined the inhibitory potency of 2a-c on Ab 1-42 self-aggregation, the interference of 2a with the toxic Ab oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of Ab toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Ab and with the Ab-preformed fibrils were computationally analyzed. 2a-c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts). Results: Our prototypical pluripotent analogue 2a interferes with Ab oligomerization process thus reducing Ab oligomers-mediated toxicity in human neuroblastoma cells. 2a also disrupts preformed fibrils. Computational studies highlighted the bases governing the diversified activities of 2a. Conclusion: Converging analytical, biological, and in silico data explained the mechanism of action of 2a on Ab 1-42 oligomers formation and against Ab-preformed fibrils. This evidence, combined with toxicity data, will orient the future design of safer analogues.
RSC Advances, 2014
Parasite derived surface antigen PfEMP1 is a virulence factor of the human malaria parasite. PfEM... more Parasite derived surface antigen PfEMP1 is a virulence factor of the human malaria parasite. PfEMP1 variants have been implicated in the cytoadherence of P. falciparum infected erythrocytes (iRBC) to several binding receptors on host vascular endothelium. Among them, binding to ICAM-1 seems to be related to severe manifestations of the disease such as cerebral malaria. The binding site for iRBC has been mapped to the BED-side of the N-terminal immunoglobulin-like domain of ICAM-1, and the DE-loop appears to be critical for binding. To date (+)-EGCG is the unique small molecule anti-cytoadherence inhibitor probably mimicking the DE-loop of ICAM-1. Here we report the discovery of a tetrahydroisoquinoline derivative, a prototype of a novel class of cytoadherence inhibitors, and an analogue of the natural compound characterized by a synthetically accessible scaffold. Molecular modeling analysis of (+)-EGCG and its synthetic tetrahydroisoquinoline analogue rationalized their binding mode to PfEMP1, confirming their ability to mimic the DE-loop.
Journal of Medicinal Chemistry, 2011
Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinet... more Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective, and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.
Journal of Medicinal Chemistry, 2012
The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond accep... more The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4ones were examined in vitro (against Plasmodium falciparum) and in vivo (against Plasmodium berghei). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. bergheiinfected mice.
Journal of Inorganic Biochemistry, 2000
With the aim of improving the compatibility of biomaterials to be used for the construction of ca... more With the aim of improving the compatibility of biomaterials to be used for the construction of cardiovascular prosthesis, we have designed bioactive macromolecules resulting from chemical modifications of hyaluronic acid (Hyal). The stability constants of Cu(II) and Zn(II) complexes with the sulphated derivative of hyaluronic acid (HyalS) were evaluated. Two different complexes have been found 3.5 for each metal ion, CuL, Cu(OH) L and ZnL, Zn(OH) L (L means the disaccharide unit of the ligands) in aqueous solution at 378C. The 2 2 dihydroxo Cu(II) complex was present in high percentage at pH57.4. On the contrary, the Zn(II) ion was present with a relatively low percentage of both complexes. The ability to stimulate endothelial cell adhesion and migration was evaluated for Hyal, HyalS and their 3.5 (4.5)2 complexes with Cu(II) and Zn(II) ions. The results revealed that Hyal and [Cu(OH) HyalS ] induced cell adhesion, while 2 3. 5 (2.5)2 (4.5)2 [ZnHyalS ] and [Zn(OH) HyalS ] inhibited the process. The chemotactic activity of increasing concentrations of the above 3.5 2 3.5 (4.5)2 complexes was also evaluated, demonstrating that [Cu(OH) HyalS ] complex at 1 mM concentration was the most active in 2 3. 5 inducing cell migration. These results have been also strengthened by analysing adherent cell migration in agarose. In conclusion, sulphated hyaluronic acid coordinated to Cu(II) seems to be a promising matrix molecule for the construction of cardiovascular prosthesis.
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2005
The effect of hyaluronan-based hydrogel with a cross-linking degree of 50% (i.e., the amount of c... more The effect of hyaluronan-based hydrogel with a cross-linking degree of 50% (i.e., the amount of carboxylate groups involved in the cross-lining reaction) (Hyal 50%), loaded with an anti-inflammatory drug (ibuprofen-lysine) for local administration in the osteoarthritic knee was evaluated. The kinetic of drug release from Hyal 50% hydrogel was performed in vitro by a continuous flow system. The release was studied at three different rates (0.375, 0.073, and 0.005 mL/s), and for the slowest one a period of 8 days was necessary to receive the complete release of the drug. A chondral defect was caused in the right femoral medial condyle of 24 rabbits. Twelve animals were treated with Hyal 50%+ibuprofen-lysine and 12 with Hyal 50% by percutaneous injection. The treatments were repeated every 10 days, for three or five times. At 30 and 50 days, no significant differences were observed between the groups (mean score at 30 days: 4.4+/-0.6 in Hyal 50%-treated group and 5.1+/-0.7 in Hyal 50% +Ibuprofen-lysine-treated group; mean score at 50 days: 6.9+/-0.6 in Hyal 50%-treated group and 7.1+/-0.6 in Hyal 50%+ Ibuprofen-lysine-treated group). A significant difference was observed in bone mineral density of the total tibia of rabbits treated by Hyal 50% + Ibuprofen-lysine in comparison with those treated only by Hyal 50%. The positive effects of Hyal 50% on chondral lesions were maintained in the presence of ibuprofen-lysine with the adjunctive effect of an increased limb usage, most likely due to less pain and discomfort.
Journal of Medicinal Chemistry, 2020
International Journal of Artificial Organs, 2009
The aim of this paper was to study the influence of chemical and topographical signals on cell be... more The aim of this paper was to study the influence of chemical and topographical signals on cell behavior and to obtain a heterotypic cell-cell interaction on microstructured domains. The polysaccharide hyaluronic acid (Hyal) was photoimmobilized on glass surfaces in order to obtain a pattern with squares and rectangles of different dimensions and chemistry. The microstructured surfaces were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The behavior of human coronary artery endothelial cells (HCAEC) and human tumoral dermal fibroblasts (C54) was investigated on these micropatterned surfaces by adhesion studies. Moreover heterotypic interaction among C54 and HCAEC adherent on patterned surfaces was evaluated by time-lapse video microscopy Surface analysis revealed the presence of a pattern consisting of alternating glass and Hyal microstructures whose dimensions decreased from the center to the edge of the sample. Neither HCAEC nor C54 adhered t...
Lymphology, 2004
The implant of a biocompatible device capable of guiding lymphatic vessel regeneration in patient... more The implant of a biocompatible device capable of guiding lymphatic vessel regeneration in patients who underwent removal of lymph nodes might contribute to restoring an efficient lymphatic drainage and help to prevent the occurrence of lymphedema. The aim of this study was to evaluate whether a microstructured surface could provide a guidance for the growth of cultured lymphatic endothelial cells. The presence of microstructures on a surface permits the control of cell adhesion, migration, proliferation, and differentiation. We report here that lymphatic endothelial cells align on microstructures of alternating hyaluronan and aminosylanized glass stripes obtained by photoimmobilization. Cells consistently spread and proliferate only on aminosylanized glass. They orient parallel to the longitudinal axis of the stripe. A pattern of alternating stripes of aminosylanized glass uniformly covered by elongated cells and of hyaluronan devoid of cells eventuallyforms. The presence of alpha(v...
Journal of medicinal chemistry, 2013
Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series o... more Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABAB receptor by potentiating GTPγS stimulation induced by GABA at 2.5 and 25 μM while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.
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Papers by Stefania Lamponi