Antiproliferative Activity of Functionalized Histidine-derived Au(I) bis-NHC Complexes for Bioconjugation

Christian H.G. Jakob; Bruno Dominelli; Eva M. Hahn; Tobias O. Berghausen; Teresa Pinheiro; Fernanda Marques; Robert M. Reich; João D.G. Correia; Fritz E. Kühn

doi:10.1002/asia.202000620

Antiproliferative Activity of Functionalized Histidine-derived Au(I) bis-NHC Complexes for Bioconjugation

Christian H.G. Jakob, Bruno Dominelli, Eva M. Hahn, Tobias O. Berghausen, Teresa Pinheiro, Fernanda Marques, Robert M. Reich, João D.G. Correia, Fritz E. Kühn

Associate Professorship of Molecular Catalysis

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2754-2762
Number of pages	9
Journal	Chemistry - An Asian Journal
Volume	15
Issue number	17
DOIs	https://doi.org/10.1002/asia.202000620
State	Published - 1 Sep 2020

Keywords

Amino acid
Anti-cancer
Gold
Medicinal Chemistry
N-Heterocyclic Carbenes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/asia.202000620

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title = "Antiproliferative Activity of Functionalized Histidine-derived Au(I) bis-NHC Complexes for Bioconjugation",

abstract = "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.",

keywords = "Amino acid, Anti-cancer, Gold, Medicinal Chemistry, N-Heterocyclic Carbenes",

author = "Jakob, {Christian H.G.} and Bruno Dominelli and Hahn, {Eva M.} and Berghausen, {Tobias O.} and Teresa Pinheiro and Fernanda Marques and Reich, {Robert M.} and Correia, {Jo{\~a}o D.G.} and K{\"u}hn, {Fritz E.}",

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year = "2020",

month = sep,

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doi = "10.1002/asia.202000620",

language = "English",

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AU - Jakob, Christian H.G.

AU - Dominelli, Bruno

AU - Hahn, Eva M.

AU - Berghausen, Tobias O.

AU - Pinheiro, Teresa

AU - Marques, Fernanda

AU - Reich, Robert M.

AU - Correia, João D.G.

AU - Kühn, Fritz E.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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.

AB - 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.

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KW - Gold

KW - Medicinal Chemistry

KW - N-Heterocyclic Carbenes

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JO - Chemistry - An Asian Journal

JF - Chemistry - An Asian Journal

IS - 17

ER -

Antiproliferative Activity of Functionalized Histidine-derived Au(I) bis-NHC Complexes for Bioconjugation

Abstract

Keywords

UN SDGs

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