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Toward Angiogenesis Inhibitors Based on the Conjugation of Organometallic Platinum(II) Complexes to RGD Peptides
Author(s) -
Zamora Ana,
Gandioso Albert,
Massaguer Anna,
Buenestado Silvia,
Calvis Carme,
Hernández Jose Luis,
Mitjans Francesc,
Rodríguez Venancio,
Ruiz José,
Marchán Vicente
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800282
Subject(s) - angiogenesis , chemistry , combinatorial chemistry , cancer research , platinum , stereochemistry , pharmacology , biochemistry , computational biology , medicine , biology , catalysis
A novel conjugate between a cyclometalated platinum(II) complex with dual antiangiogenic and antitumor activity and a cyclic peptide containing the RGD sequence (‐Arg‐Gly‐Asp‐) has been synthesized by combining solid‐ and solution‐phase methodologies. Although peptide conjugation rendered a non‐cytotoxic compound in all tested tumor cell lines (± α V β 3 and α V β 5 integrin receptors), the antiangiogenic activity of the Pt‐c(RGDfK) conjugate in human umbilical vein endothelial cells at sub‐cytotoxic concentrations opens the way to the design of a novel class of angiogenesis inhibitors through conjugation of metallodrugs with high antiangiogenic activity to cyclic RGD‐containing peptides or peptidomimetic analogues.