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Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis ‐NHC Complexes for Bioconjugation
Author(s) -
Jakob Christian H. G.,
Dominelli Bruno,
Hahn Eva M.,
Berghausen Tobias O.,
Pinheiro Teresa,
Marques Fernanda,
Reich Robert M.,
Correia João D. G.,
Kühn Fritz E.
Publication year - 2020
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.202000620
Subject(s) - bioconjugation , amide , chemistry , cytotoxicity , cysteine , hydrolysis , histidine , thiol , combinatorial chemistry , peptide , in vitro , stereochemistry , amino acid , organic chemistry , biochemistry , enzyme
A series of histidine derived Au(I) bis ‐NHC complexes bearing different ester, amide and carboxylic acid functionalities as well as wingtip substituents is synthesized and characterized. The stability in aqueous media, in vitro cytotoxicity in a set of cancer cell lines (MCF7, PC3 and A2780/A2780cisR) along with the cellular uptake are evaluated. Stability tests suggest hydrolysis of the ester within 8 h, which might lead to deactivation. Furthermore, the bis ‐NHC system shows a sufficient stability against cysteine and the thiol containing peptide GSH. The benzyl ester and amide show the highest activity comparable to the benchmark compound cisplatin, with the ester only displaying a slightly lower cytotoxicity than the amide. A cellular uptake study revealed that the benzyl ester and the amide could have different intracellular distribution profiles but both complexes induce perturbations of the cellular physiological processes. The simple modifiability and high stability of the complexes provides a promising system for upcoming post modifications to enable targeted cancer therapy.