Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

Constantinos G Neochoritis, Maryam Kazemi Miraki, Eman M M Abdelraheem, Ewa Surmiak, Tryfon Zarganes-Tzitzikas, Beata Łabuzek, Tad A Holak, Alexander Dömling

OnderzoeksoutputAcademicpeer review

4 Citaten (Scopus)
215 Downloads (Pure)


Macrocycles were designed to antagonize the protein-protein interaction p53-MDM2 based on the three-finger pharmacophore F19W23L25. The synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library for p53-MDM2 inhibition by fluorescence polarization and 1H,15N HSQC NMR measurements confirm MDM2 binding.

Originele taal-2English
Pagina's (van-tot)513-520
Aantal pagina's8
TijdschriftBeilstein Journal of Organic Chemistry
StatusPublished - 20-feb-2019

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