Toward Angiogenesis Inhibitors Based on the Conjugation of Organometallic Platinum(II) Complexes to RGD Peptides

• Published in: ChemMedChem Vol. 13; no. 17; pp. 1755 - 1762
• Main Authors: Zamora, Ana, Gandioso, Albert, Massaguer, Anna, Buenestado, Silvia, Calvis, Carme, Hernández, Jose Luis, Mitjans, Francesc, Rodríguez, Venancio, Ruiz, José, Marchán, Vicente
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.09.2018; Wiley Subscription Services, Inc; Wiley-VCH
• Subjects: Angiogenesis; Angiogenesis inhibitors; Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Angiogènesi; Antiangiogenics; Anticancer properties; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Compostos organometàl·lics; Conjugates; Conjugation; Cytotoxicity; Càncer; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Endothelial cells; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Inhibitors; Life Sciences & Biomedicine; Molecular Structure; Neovascularization; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; Organometallic compounds; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Peptides; Pharmacology & Pharmacy; Platinum; Pèptids; Receptors; Science & Technology; Structure-Activity Relationship; Tumor cell lines; Umbilical vein; inhibitors; APOPTOSIS; angiogenesis; peptides; ANTITUMOR; CILENGITIDE; STRATEGIES; platinum; ANTIANGIOGENIC ACTIVITY; RUTHENIUM(II); cancer; AGENTS; IRIDIUM COMPLEX; INTEGRIN ALPHA(V)BETA ANTAGONISTS
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201800282

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 (± αVβ3 and αVβ5 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. Platinum‐backed peptides: Conjugates of cyclometalated platinum(II) complexes and RGD peptides are investigated as potential angiogenesis inhibitors. 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 angiogenesis inhibitors through conjugation of metallodrugs with high antiangiogenic activity to cyclic RGD‐containing peptides or peptidomimetic analogues.