ETD system

Electronic theses and dissertations repository

 

Tesi etd-10222012-104339


Thesis type
Tesi di laurea specialistica LC5
Author
FANELLI, SERENA
URN
etd-10222012-104339
Title
Synthesis and biological evalutation of novel N,N-dialkyl-2-arylindol-3-ylglyoxylamide TSPO ligands.
Struttura
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Commissione
relatore Dott.ssa Taliani, Sabrina
relatore Prof.ssa Martini, Claudia
Parole chiave
  • TSPO
  • neuroprotective
Data inizio appello
14/11/2012;
Consultabilità
completa
Riassunto analitico
A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives was design, synthesized and tested as TSPO ligands. The SARs of these compounds were rationalized in light of the pharmacophore/topological model of TSPO binding site made up of three lipophilic pockets (L1, L3 and L4) and a H-bond donor group (H1). The aim of this work is the design and the synthesis of a novel series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide featuring suitable substituentes on the indole nucleus for good pharmacokinetic parameters. The affinity towards TSPO of all the new compounds was tested by binding assays performed on rat kidney membranes. For those compounds which showed a Ki value in the sub-nanomolar range, the ability to induce functional effects trough the TSPO was also tested. In particular we carried out experiments on cell growth in metabolic stress conditions. The effects of some compounds (the most promising ones in term of affinity) were evaluated by proliferation MTS assay and crystal violet staining. The obtained results showed an increase in cell growth after 48 hours of treatment with compounds, in respect to the control, suggesting their neuroprotective action.
File