Biological evaluation of pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea derivatives as potential anti-angiogenetic agents in the treatment of neuroblastoma
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Barbara Marengo1,*, Elda Meta2,3,4,*, Chiara Brullo2, Chiara De Ciucis1, Renata Colla1, Andrea Speciale5, Ombretta Garbarino1, Olga Bruno2,* and Cinzia Domenicotti1,*
1 Department of Experimental Medicine, General Pathology Section, University of Genoa, Genoa, Italy
2 Department of Pharmacy, Medicinal Chemistry Section, University of Genoa, Genoa, Italy
3 Department of Oncology, Laboratory of Angiogenesis and Vascular Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium
4 Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
5 UOC Mutagenesis and Cancer Prevention, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
* These authors contributed equally to this work
Keywords: tumor angiogenesis; neuroblastoma; vascular mimicry; pyrazolyl-urea derivatives; dihydro-imidazo-pyrazolyl-urea derivatives
Received: April 23, 2020 Accepted: August 11, 2020 Published: September 15, 2020
Pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea compounds (STIRUR 13, STIRUR 41 and BUR 12) have been demonstrated to exert a strong inhibitory effect on interleukin 8 or N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis of human neutrophils. Since the migration of cancer cells is comparable to that of neutrophils, the purpose of this study is to evaluate the biological effect of STIRUR 13, STIRUR 41 and BUR 12 on ACN and HTLA-230, two neuroblastoma (NB) cell lines with different degree of malignancy. HTLA-230 cells, stage-IV NB cells, have high plasticity and can serve as progenitors of endothelial cells. The results herein reported show that the three tested compounds were not cytotoxic for both NB cells and did not alter their clonogenic potential. However, all compounds were able to inhibit the ability of HTLA-230 to form vascular-like structures. On the basis of these findings, pyrazolyl-urea and dihydro-imidazo-pyrazolyl-urea derivatives could be proposed as agents potentially effective in counteracting NB malignancy by inhibiting cell migration and tumor angiogenesis which represent important hallmarks responsible for cancer survival and progression.
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