Iacopetta Domenico, Costabile Chiara, La Chimia Marina, Mariconda Annaluisa, Ceramella Jessica, Scumaci Domenica, Catalano Alessia, Rosano Camillo, Cuda Giovanni, Sinicropi Maria Stefania, Longo Pasquale
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy.
Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
ACS Med Chem Lett. 2023 Oct 10;14(11):1567-1575. doi: 10.1021/acsmedchemlett.3c00360. eCollection 2023 Nov 9.
-Heterocyclic carbene (NHC) metal complexes are attracting scientists' interest as an alluring class of metallodrugs. Indeed, the versatile functionalization of NHC ligands makes them optimal scaffolds to be developed in medicinal chemistry. Besides, amino acids are great biological ligands for metals, such as silver and gold, even though their use is still under-investigated. Aiming to shed light on the anticancer properties of this kind of complex, we investigated a series of silver and gold complexes, stabilized by NHC ligands and bearing carboxylate salts of -butyloxycarbonyl (Boc)--protected glycine and l-phenylalanine as anionic ligands. The most active complexes, and , powerfully affect the growth of MDA-MB-231 breast cancer cells, with IC values in the low nanomolar range. Further studies demonstrated the blockade of the human topoisomerase I activity and actin polymerization reaction at 0.001 μM. These unique features make these complexes very interesting and worthy to be used for future studies.
