Glyco-Molecular tools as modulators-inhibitors-drugs
1)Study of the Role of the Hexosamine Biosynthetic Pathway in Cancer by means of Chemical Molecular Tools (coll. Dr. Chiaradonna BTBS)
Design and synthesis of molecular tools as modulators of the hexosamine biosynthetic pathway. In particular we focus on the inhibition of AGM1. In this project we design and synthesize glycomimetics analogues of N-acetylglucosamine-6-phosphate, the natural substrate of the enzyme AGM1. We have already identified a potent lead compound able to reduce tumor growth in vivo and are working on second generation derivatives of the lead. Our LEAD FR054 is at present used by different international groups!
Design and synthesis of molecular tools as modulators of the hexosamine biosynthetic pathway. In particular we focus on the inhibition of AGM1. In this project we design and synthesize glycomimetics analogues of N-acetylglucosamine-6-phosphate, the natural substrate of the enzyme AGM1. We have already identified a potent lead compound able to reduce tumor growth in vivo and are working on second generation derivatives of the lead. Our LEAD FR054 is at present used by different international groups!
ARSENICAL C-GLYCOSIDES AS ANTITUMORAL AGENTS
C‐Glucoside derivatives covalently linked to the arsenic atom in different oxidation states have been synthesized. The C‐glucoside conjugated to the phenyldithioarsolan group, showed promising antiproliferative activity on human neuroblastoma cells (SK‐N‐BE).
At present we are developing new compounds in collaboration with prof. Marco Salvetti (university La Sapienza) and the group of Prof. Antonella Arcella (Neuromed).
At present we are developing new compounds in collaboration with prof. Marco Salvetti (university La Sapienza) and the group of Prof. Antonella Arcella (Neuromed).
2)Synthesis of Gastrin Releasing Peptide Receptor (GRP-R) ligands for tumor targeting (collaboration: Dr.ssa Cristina Airoldi BTBS, Dr.ssa Cecilia Ceresa)
GRPRs as target for cancer therapy. Gastrin-Releasing Peptide Receptors (GRPR) are transmembrane G-proteins coupled receptors that trigger different signaling transduction pathways, resulting, among which, in the stimulation of cell proliferation. Although GRPR are poorly distributed in normal tissues, it has been shown that they are significantly involved in the pathogenesis of different human cancers, including lung (small and non-small cell type), breast, prostate, exocrine pancreas, head and neck squamous cell, and glioblastoma cancers. In addition, they are recently emerged as tumoral markers in early prostate and breast cancer diagnosis. For these reasons, the research of new GRPR ligands as antagonists or carriers for cytotoxic and imaging molecular tools might be a promising strategy for the treatment and diagnosis of human tumoral malignancies.
GRPRs as target for cancer therapy. Gastrin-Releasing Peptide Receptors (GRPR) are transmembrane G-proteins coupled receptors that trigger different signaling transduction pathways, resulting, among which, in the stimulation of cell proliferation. Although GRPR are poorly distributed in normal tissues, it has been shown that they are significantly involved in the pathogenesis of different human cancers, including lung (small and non-small cell type), breast, prostate, exocrine pancreas, head and neck squamous cell, and glioblastoma cancers. In addition, they are recently emerged as tumoral markers in early prostate and breast cancer diagnosis. For these reasons, the research of new GRPR ligands as antagonists or carriers for cytotoxic and imaging molecular tools might be a promising strategy for the treatment and diagnosis of human tumoral malignancies.
Glyco-nanoparticles (G-NPs)
(G-NPs) constitute versatile nanoplatforms for drug delivery and targeting.
3) PLGA Nanoparticles surface decorated with Glyco-and Glycodendrimer for targeted drug delivery.
Collaboration: Prof. Paola Allavena Istituto di ricerca Humanitas
Nowadays, surface functionalized nanoparticles (NPs) are gaining great importance in the biomedical field due to the emerging role of nanomedicine. Nanotechnology is orienteering towards the development of nano-medical devices as drug delivery and diagnostic systems with improved properties and reduced side effects if compared to traditional medicine.
PLGA NPs presenting carbohydrate surface decoration for specific tissue targeting; cytotoxic drug encapsulation and fluorescently labelled. The present work consists on the preparation of biocompatible, surface decorated and drug loaded PLGA-NPs for tumor targeting and treatment.
3) PLGA Nanoparticles surface decorated with Glyco-and Glycodendrimer for targeted drug delivery.
Collaboration: Prof. Paola Allavena Istituto di ricerca Humanitas
Nowadays, surface functionalized nanoparticles (NPs) are gaining great importance in the biomedical field due to the emerging role of nanomedicine. Nanotechnology is orienteering towards the development of nano-medical devices as drug delivery and diagnostic systems with improved properties and reduced side effects if compared to traditional medicine.
PLGA NPs presenting carbohydrate surface decoration for specific tissue targeting; cytotoxic drug encapsulation and fluorescently labelled. The present work consists on the preparation of biocompatible, surface decorated and drug loaded PLGA-NPs for tumor targeting and treatment.
Figure: functionalization and characterization of PLGA polymer, and NPs assemblage
(4) Cellulose Nanocrystals (CNCs): cellulose based nanoparticles
a)Develop CNCs as novel nanomedical device for bone targeting
Collaboration with Dr. Luca Zoia DISAT, Dr. Paolo Bigini Mario Negri Institute for pharmacological research
b) Use of CNCs as novel antibacterial agents.
collaboration Dr. Patrizia Di Gennaro BTBS
a)Develop CNCs as novel nanomedical device for bone targeting
Collaboration with Dr. Luca Zoia DISAT, Dr. Paolo Bigini Mario Negri Institute for pharmacological research
b) Use of CNCs as novel antibacterial agents.
collaboration Dr. Patrizia Di Gennaro BTBS
Passed... projects
ANTIAMILOIDOGENIC COMPOUNDS for Alzheimer's Disease (FP VII PROGRAM: CP-IP 212043-2 NAD)
In the research group we developed Glycofused tricyclic compounds as ligands able to interact with amyloid beta-peptides and to interfere with their aggregation into plaques, which represent one of the hallmarks of Alzheimer's Disease
C-GLYCOSIDES AS ANTIINFLAMMATORY AGENTS
Come dansyl with me!
A small library of naphthyl gluco derivatives was synthesised from methyl α‐D‐glucopyranoside without protection/deprotection steps. One library member, dansyl C‐glucoside 5, showed an extraordinary anti‐inflammatory activity, protecting 100 % of mice from sepsis at a dose of 25 μg kg−1. |
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IMINOSUGARS AS ENZYMATIC INHYBITORS
Iminosugars are important carbohydrate processing enzymes inhibitors. In our lab we have developed synthetic approaches for the synthesis of iminosugars and derivatives starting from commercial carbohydrates.
Cationic derivatives have shown inhibition properties also towards bacteria.
Cationic derivatives have shown inhibition properties also towards bacteria.