Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10590989 | Bioorganic & Medicinal Chemistry Letters | 2014 | 6 Pages |
Abstract
Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A165/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization.
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Authors
Wang-Qing Liu, Valentino Megale, Lucia Borriello, Bertrand Leforban, Matthieu Montès, Elodie Goldwaser, Nohad Gresh, Jean-Philip Piquemal, Reda Hadj-Slimane, Olivier Hermine, Christiane Garbay, Françoise Raynaud, Yves Lepelletier, Luc Demange,