University of Groningen Development of novel anticancer agents for protein targets Estrada Ortiz, Natalia

University of Groningen

Development of novel anticancer agents for protein targets

Estrada Ortiz, Natalia

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2017

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Estrada Ortiz, N. (2017). Development of novel anticancer agents for protein targets. University of

Groningen.

Copyright

Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policy

If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

P

ROPOSITIONS

For the thesis

D

N

A

A

P

T

1. More active and selective compounds with improved metabolic profile, reduced side effects and dual MDM2 and MDMX targeting function should be developed as inhibitors of MDM2/X-p53 interaction.

2. Conserved water clusters in the co-crystal structures of MDM2 with its inhibitors are potential spots for the design of MDM2 inhibitors, where extra hydrogen bond formation can stabilize the binding and increase the potency of inhibitors of p53/MDM2 interactions.

3. Artificial macrocycles targeting the large hydrophobic area formed in the interphase of p53-MDM2 can be potent inhibitors with potential superior ADMET properties compared to currently available scaffolds.

4. Although metals and metal containing compounds have been used for therapeutic purposes since ancient times, they are still surprising us with new therapeutic applications.

5. Gold-based complexes are particularly interesting as anticancer drugs due to their different possible oxidation states, stability and ligand exchange reactions, which confer them different mechanisms of activity compared to the currently available metal containing drugs.

6. PCTS technologies allow us to obtain valuable knowledge on the structure-toxicity relationship, uptake, accumulation and mechanism of toxicity of experimental compounds, enabling selection of better candidates with improved therapeutic properties and reduced toxicity in healthy tissue.

7. "Above all, don't fear difficult moments. The best comes from them." Rita Levi-Montalcini