Leonardo Baldassarre

Publications (7) View all

• Source

  Available from: Ivana Cacciatore

  Article: Quorum Sensing Inhibitor FS3-coated Vascular Graft Enhances Daptomycin Efficacy in a Rat Model of Staphylococcal Infection.

  Oscar Cirioni, Federico Mocchegiani, Ivana Cacciatore, Jacopo Vecchiet, Carmela Silvestri, Leonardo Baldassarre, Claudio Ucciferri, Elena Orsetti, Pamela Castelli, Mauro Provinciali, Marco Vivarelli, Erika Fornasari, Andrea Giacometti
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  ABSTRACT: The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: i)intraperitoneal daptomycin, ii) FS3-soacked graft, and iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.
  Peptides 12/2012; · 2.43 Impact Factor
• Article: (R)-α-Lipoyl-Glycyl-L-Prolyl-L-Glutamyl Dimethyl Ester Codrug as a Multifunctional Agent with Potential Neuroprotective Activities.

  Ivana Cacciatore, Leonardo Baldassarre, Erika Fornasari, Catia Cornacchia, Antonio Di Stefano, Piera Sozio, Laura Serafina Cerasa, Antonella Fontana, Stefania Fulle, Ester Sara Di Filippo, Rita Maria Laura La Rovere, Francesco Pinnen
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  ABSTRACT: The (R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug (LA-GPE, 1) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA-GPE to penetrate the blood-brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA-GPE against the cytotoxicity induced by 6-hydroxydopamine (6-OHDA) and H(2) O(2) on the human neuroblastoma cell line SH-SY5Y by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH-dependent permeability profile. Furthermore, LA-GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H(2) O(2) - and 6-OHDA-induced neurotoxicity in SH-SY5Y cells.
  ChemMedChem 09/2012; · 3.15 Impact Factor
• Article: Synthesis of short cationic antimicrobial peptidomimetics containing arginine analogues.

  Leonardo Baldassarre, Francesco Pinnen, Catia Cornacchia, Erika Fornasari, Luigina Cellini, Marina Baffoni, Ivana Cacciatore
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  ABSTRACT: Worldwide efforts are underway to develop new antimicrobial agents against bacterial resistance. To identify new compounds with a good antimicrobial profile, we designed and synthesized two series of small cationic antimicrobial peptidomimetics (1-8) containing unusual arginine mimetics (to introduce cationic charges) and several aromatic amino acids (bulky moieties to improve lipophilicity). Both series were screened for in vitro antibacterial activity against a representative panel of Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacterial strains, and Candida albicans. The biological screening showed that peptidomimetics containing tryptophan residues are endowed with the best antimicrobial activity against S. aureus and S. epidermidis in respect to the other synthesized derivatives (MIC values range 7.5-50 µg/ml). Moreover, small antimicrobial peptidomimetics derivatives 2 and 5 showed an appreciable activity against the tested Gram-negative bacteria and C. albicans. The most active compounds (1-2 and 5-6) have been tested against Gram-positive established biofilm, too. Results showed that the biofilm inhibitory concentration values of these compounds were never up to 200 µg/ml. The replacement of tryptophan with phenylalanine or tyrosine resulted in considerable loss of the antibacterial action (compounds 3-4 and 7-8) against both Gram-positive and Gram-negative bacterial strains. Furthermore, by evaluating hemolytic activity, the synthesized compounds did not reveal cytotoxic activities, except for compound 5.
  Journal of Peptide Science 07/2012; 18(9):567-78. · 1.80 Impact Factor
• Article: Discovery of novel RIP derivatives by alanine scanning for the treatment of S. aureus infections.

  Leonardo Baldassarre, Erika Fornasari, Catia Cornacchia, Oscar Cirioni, Carmela Silvestri, Pamela Castelli, Andrea Giacometti, Ivana Cacciatore
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  ABSTRACT: Alanine scanning has been used to define the key residues for the activity of RNA III inhibiting peptide (RIP) against S. aureus. We have found that the threonine residue in position 5 is detrimental for the RIP activity, while the removal of serine (P2) and phenylalanine (P7), afforded the most active RIP derivatives (2 and 7). Moreover, we have identified the small RIP derivative (9), corresponding to the sequence H-Ser-Pro-Trp-Thr-NH2, which displayed the best antistaphylococcal activity.
  Medicinal Chemistry Communication 05/2013; · 2.80 Impact Factor
• Source

  Available from: Ivana Cacciatore

  Article: Recent advances in the treatment of neurodegenerative diseases based on GSH delivery systems.

  Ivana Cacciatore, Leonardo Baldassarre, Erika Fornasari, Adriano Mollica, Francesco Pinnen
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  ABSTRACT: Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD.
  Oxidative Medicine and Cellular Longevity 01/2012; 2012:240146.