1951402-78-0Relevant articles and documents
The discovery of new cytotoxic pyrazolopyridine derivatives
Giannouli, Vassiliki,Lougiakis, Nikolaos,Kostakis, Ioannis K.,Pouli, Nicole,Marakos, Panagiotis,Skaltsounis, Alexios-Leandros,Nam, Sangkil,Jove, Richard,Horne, David,Tenta, Roxane,Pratsinis, Harris,Kletsas, Dimitris
, p. 5229 - 5233 (2016)
A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC50values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G0/G1phase and induce apoptosis, as determined by the appearance of apoptotic nuclei.
Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis
Michailidou, Maria,Giannouli, Vassiliki,Kotsikoris, Vasilios,Papadodima, Olga,Kontogianni, Georgia,Kostakis, Ioannis K.,Lougiakis, Nikolaos,Chatziioannou, Aristotelis,Kolisis, Fragiskos N.,Marakos, Panagiotis,Pouli, Nicole,Loutrari, Heleni
, p. 143 - 157 (2016)
Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endothelial cells. Four of the synthesized compounds, possessing analogous substitution pattern, were found able to inhibit at low micromolar concentrations endothelial cell proliferation, migration and differentiation, constitutively or in response to Vascular Endothelial Growth Factor (VEGF) and to attenuate VEGF-induced phosphorylation of VEGF receptor-2 and downstream kinases AKT and ERK1/2. Administration of effective compounds in mice delayed the growth of syngeneic Lewis lung carcinoma transplants and reduced tumor microvessel density, without causing toxicity. Genome-wide microarray and gene ontology analyses of treated endothelial cells revealed derivative 18c as the most efficient modulator of gene expression and mitotic cell cycle/cell divisiong along with ? cholesterol biosynthesis? as the most significantly altered biological processes.
