Synthesis and Biological Evaluation of a c(RGDyK) Peptide Conjugate of SRPIN803

George Leonidis; Panagiotis Dalezis; Dimitrios Trafalis; Dimitris Beis; Panagiota Giardoglou; Anastasia Koukiali; Ioanna Sigala; Eleni Nikolakaki; Vasiliki Sarli

doi:10.1021/acsomega.1c04576

Synthesis and Biological Evaluation of a c(RGDyK) Peptide Conjugate of SRPIN803

ACS Omega. 2021 Oct 14;6(42):28379-28393. doi: 10.1021/acsomega.1c04576. eCollection 2021 Oct 26.

Authors

George Leonidis¹, Panagiotis Dalezis², Dimitrios Trafalis², Dimitris Beis³, Panagiota Giardoglou³, Anastasia Koukiali¹, Ioanna Sigala¹, Eleni Nikolakaki¹, Vasiliki Sarli¹

Affiliations

¹ Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
² Laboratory of Pharmacology, Medical School National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece.
³ Zebrafish Disease Model Lab, Biomedical Research Foundation Academy of Athens, Athens 115 27, Greece.

Abstract

In the present study, SRPIN803 and c(RGDyK)-SRPIN803 hybrid compounds were efficiently synthesized and evaluated for their stability in human plasma and buffers of pH 7.4 and 5.2. The hybrids were mainly cytostatic against a panel of tested cancer cells, whereas one c(RGDyK)-SRPIN803 hybrid, geo35, was the most active compound in this screen and was cytotoxic against cell lines MCF7 and MRC5 with IC₅₀ values of 61 and 63 μM, respectively. SRPIN803 and geo35 exhibited antiangiogenic activity in zebrafish embryos, and this effect was dose-dependent. Although c(RGDyK)-SRPIN803 hybrid compounds were found less potent compared to SRPIN803, they have shown activities interesting enough to illustrate the potential of this approach for the development of a new class of antiangiogenic compounds.