Research Article

Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

Laboratory of Pharmacology, Medical School National & Kapodistrian University of Athens, 75 Mikras Asias Street, Athens, 11527, Greece

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George Leonidis

Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

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Spyridon Bousis

Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

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Dimitrios Trafalis

https://orcid.org/0000-0003-4066-9780

Laboratory of Pharmacology, Medical School National & Kapodistrian University of Athens, 75 Mikras Asias Street, Athens, 11527, Greece

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Francesca Bianchini

*Author for correspondence:

E-mail Address: sarli@chem.auth.gr

Department of Experimental & Clinical Biomedical Sciences, University of Florence, V.le GB Morgagni 50, Firenze, 50134, Italy

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Vasiliki Sarli

**Author for correspondence:

E-mail Address: francesca.bianchini@unifi.it

https://orcid.org/0000-0002-6128-8277

Department of Chemistry, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 54124, Greece

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Published Online:16 Apr 2021https://doi.org/10.4155/fmc-2020-0309

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Abstract

Cucurbitacins (CUCUs) are triterpenoids known to display potent cytotoxic effects; however, their clinical application is limited due to poor pharmacokinetics and systemic toxicity. This work focuses on the development of c(RGDyK)–CUCU conjugates for the selective delivery of CUCUs to integrin-overexpressing cancer cells. The activity of the conjugates against various cancer cells was studied. They exhibited a mild cytostatic effect to six cancer cell lines and a cytotoxic effect against integrin-overexpressing MCF-7 and A549 cells. Their chemical and metabolic stability was extensively studied using LC–MS analysis. The conjugates maintained high affinity for α_vβ₃ integrin receptors. c(RGDyK) conjugation via a PEG linker was beneficial for CUCU-D and the resulting conjugate was approximately three-times more active than the free CUCU-D in MCF7 cells.

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Papers of special note have been highlighted as: •• of considerable interest

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Vol. 13, No. 10

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History

Received 7 October 2020

Accepted 1 March 2021

Published online 16 April 2021

Published in print May 2021

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2020-0309

Acknowledgments

The authors would like to thank A Goula and K Goulas for gathering the fruits of Ecbalium elaterium from the Trilofos region (Thessaloniki, Greece).

Financial & competing interests disclosure

The authors acknowledge support of this work by the project ‘An Open-Access Research Infrastructure of Chemical Biology and Target-Based Screening Technologies for Human and Animal Health, Agriculture and the Environment (OPENSCREEN-GR)’ (MIS 5002691) which is implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure’, funded by the Operational Programme ‘Competitiveness, Entrepreneurship and Innovation’ (NSRF 2014–2020) and cofinanced by Greece and the EU (European Regional Development Fund), and Ente Cassa di Risparmio di Firenze for grant number 2018.1014. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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Synthesis and biological studies of c(RGDyK) conjugates of cucurbitacins

Abstract

Graphical abstract

References