Research unit coordinated by Prof. Daniela Barlocco
Group leader: Prof. Daniela Barlocco
Group members: Dr. Stefania Villa, Dr. Arianna Gelain
Postdoc: Dr. Daniela Masciocchi
PhD student: : Dr. Silvia Dell’Orto
The research activity of the group is focused on the following topics:
1) Studies on compounds structurally derived from piperazines
Studies concern a series of piperazine and tropanic derivatives provided with antiviral activity Vicriviroc in phase III and Maraviroc commercially available (CelsentriÒ) characterized by a peculiar mechanism of action, namely “entry inhibitors”. In detail, they prevent the HIV from entering cells (linfocita T) inhibiting the co-receptor CCR5 . Biological assays are performed at Immunology of HIV Unit at Ospedale San Raffaele in Milan. In addition, NMR and modelling studies in collaboration with the University of Pavia and the Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina of the University of Milan support this project.
2) Design and synthesis of potential STATs (Signal Transduction and Activators of Transcription) inhibitors as antitumor agents
STATs are cytosolic proteins and their activated forms are able to transduce extracellular signals from the membrane to the nucleus. These proteins are over-expressed in a number of tumours. Since STAT3 and STAT5 inhibition selectively cause apoptosis in tumour cells, they represents an efficient target for the treatment of cancer. In details our studies are ongoing on:
a) STAT3 inhibitors: 1,2,5-oxadiazole derivatives, evaluated in collaboration with KRIBB Institute (Daejeon, Korea) and University of Shizuoka (Shizuoka, Japan)
b) STAT5 inhibitors: benzoimidazoyl and amidic derivatives, tested in collaboration with Università di Modena e Reggio Emilia (Modena, Italy) and the Kimmel Cancer Center (KCC) of the Thomas Jefferson, University of Philadelphia (Philadelphia, USA).
3) Synthesis of Acyl-CoA Cholesterol Acyl Transferase (ACAT) inhibitors as hypocholesterolemic agents
Since ACAT exists in two isomeric forms, namely ACAT1 and ACAT2, the aim of this project is to develop selective inhibitors, which would be useful in the treatment of several pathologies including Alzheimer’s disease, hypercholesterolemia and related pathologies. In particular, the project is aimed at the synthesis of several heterocyclic derivatives, structurally related to the potent but non-selective ACAT inhibitor DUP-127. Enzyme inhibition assays are performed at the KRIBB Institute (Daejeon, Korea).
4) Studies on potential antimalarial agents
The aim of the project is the identification of novel antimalarial agents having a 3,9-diazabicyclo system variously substituted. The biological assays are performed by the group coordinated by Prof. Donatella Taramelli (University of Milan, Italy)
5) Novel materials for medical devices based on biofunctionalized surfaces with antifouling activity
Cariplo Foundation Project, www.anfomat.unimi.it