Synthesis, characterization, and antileishmanial activity of neutral N-heterocyclic carbenes gold(I) complexes

Zhang, Chen; Bourgeade‐Delmas, Sandra; Álvarez, Álvaro; Valentin, Alexis; Hemmert, Catherine; Gornitzka, Heinz

doi:10.1016/j.ejmech.2017.10.060

Cited by 51 publications

(45 citation statements)

References 37 publications

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“…The carbene precursors 2 and 3 (Scheme ) were synthesized as described . In the case of proligands 1 and 4 , excess 1‐benzylimidazole was heated under reflux with 1‐(2‐chloroethyl)piperidine hydrochloride and 3‐chloro‐ N , N ‐dimethylpropylamine hydrochloride, respectively, in acetonitrile.…”

Section: Resultsmentioning

confidence: 99%

“…The carbene precursors 2 and 3 (Scheme 1) were synthesized as described. [21] In the case of proligands 1 and 4,e xcess1benzylimidazole was heatedu nder reflux with 1-(2-chloroethyl)piperidine hydrochloride and 3-chloro-N,N-dimethylpropylamine hydrochloride, respectively,i na cetonitrile. The most notable features in the 1 Ha nd 13 CN MR spectra of the imidazolium salts are the resonances for the imidazolium protons (H2) located at d = 9.50-9.51 ppm and for the corresponding imidazolium carbon atoms (C2) in the range of d = 136.97-137.72 ppm.…”

Section: Chemistrymentioning

confidence: 99%

“…As an extension of our previouss tudies on bioactive NHC gold(I) complexes, [21][22][23][24][25][26] we prepared af amily of nitrogen-or sulfur-containing NHC gold(I) complexes. In this context, herein we present our studies on 14 NHC gold(I) complexes (four new and ten previously described compounds [21,22,24,26] ) comprising five neutral and nine cationicN HC gold(I)c omplexes. The cytotoxic activities were determined in vitro on four human cancer cell lines, including one cisplatin-resistant cell line, and on one noncancerous celll ine to evaluatet he selectivity of the complexes.…”

Section: Introductionmentioning

confidence: 99%

“…Selected bond distances []a nd angles[8]: Au1-C1 2.012(2);C1-Au1-C1 180.0.Scheme2.Gold(I) complexestested in this study. [a] Ref [21][26]…”

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Cationic and Neutral N‐Heterocyclic Carbene Gold(I) Complexes: Cytotoxicity, NCI‐60 Screening, Cellular Uptake, Inhibition of Mammalian Thioredoxin Reductase, and Reactive Oxygen Species Formation

et al. 2018

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A structurally diverse library of 14 gold(I) cationic bis(NHC) and neutral mono(NHC) complexes (NHC: N-heterocyclic carbene) was synthesized and characterized in this work. Four of them were new cationic gold(I) complexes containing functionalized NHCs, and their X-ray crystal structures are presented herein. All of the complexes were investigated for their anticancer activities in four cancer cell lines, including a cisplatin-resistant variant, and a noncancerous cell line. Seven of the cationic gold(I) complexes were found to display high and specific cytotoxic activities toward cancer cells. Two of them were even able to overcome cisplatin resistance. Two highly potent cationic complexes (11 and 15) were also submitted to the NCI-60 cancer panel for further cytotoxicity evaluation. Complex 15 showed a surprisingly high potency toward leukemia among the nine examined cancer subtypes, particularly toward the CCRF-CEM leukemia cell line with a concentration for 50 % inhibition of growth down to 79.4 nm. In addition, cationic complex 13, which demonstrated a remarkable cytotoxicity against hepatocellular carcinoma, was selected to obtain insight into the mechanistic aspects in HepG2 cells. Cellular uptake measurements were indicative of good bioavailability. By various biochemical assays, this complex was found to effectively inhibit thioredoxin reductase and its cytotoxicity toward HepG2 cells was found to be reactive oxygen species dependent.

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Section: Resultsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Selected bond distances []a nd angles[8]: Au1-C1 2.012(2);C1-Au1-C1 180.0.Scheme2.Gold(I) complexestested in this study. [a] Ref [21][26]…”

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Cationic and Neutral N‐Heterocyclic Carbene Gold(I) Complexes: Cytotoxicity, NCI‐60 Screening, Cellular Uptake, Inhibition of Mammalian Thioredoxin Reductase, and Reactive Oxygen Species Formation

et al. 2018

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“…Antileishmanial activity on L. infantum axenic amastigotes [31] L. infantum promastigotes (MHOM/MA/67/ITMAP-263, CNR Leishmania, Montpellier,F rance, expressing luciferase activity) in the logarithmic phase, cultivated in RPMI 1640 medium supplemented ChemMedChem 2018ChemMedChem , 13,2217ChemMedChem -2228 www.chemmedchem.org with 5% foetal calf serum, l-glutamine (2 mm)a nd antibiotics (100 UmL À1 penicillin and 100 mgmL À1 streptomycin), were centrifuged at 900 g for 10 min. The supernatant was removed carefully and was replaced by the same volume of RPMI 1640 complete medium at pH 5.4 and incubated for 24 ha t2 4 8C.…”

Section: Biologymentioning

confidence: 99%

Antitrypanosomatid Pharmacomodulation at Position 3 of the 8‐Nitroquinolin‐2(1H)‐one Scaffold Using Palladium‐Catalysed Cross‐Coupling Reactions

et al. 2018

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An antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecule 3-bromo-8-nitroquinolin-2(1H)-one was conducted. Twenty-four derivatives were synthesised using the Suzuki-Miyaura cross-coupling reaction and evaluated in vitro on both Leishmania infantum axenic amastigotes and Trypanosoma brucei brucei trypomastigotes. Introduction of a para-carboxyphenyl group at position 3 of the scaffold led to the selective antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1H)-one (21) with a lower reduction potential (-0.56 V) than the initial hit (-0.45 V). Compound 21 displays micromolar antitrypanosomal activity (IC =1.5 μm) and low cytotoxicity on the human HepG2 cell line (CC =120 μm), having a higher selectivity index (SI=80) than the reference drug eflornithine. Contrary to results previously obtained in this series, hit compound 21 is inactive toward L. infantum and is not efficiently bioactivated by T. brucei brucei type I nitroreductase, which suggests the existence of an alternative mechanism of action.

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Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

et al. 2020

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A series of mononuclear coordination or organometallic Au I /Au III complexes (1-9) have been comparatively studied in vitro for their antileishmanial activity against promastigotes and amastigotes, the clinically relevant parasite form, of Leishmania amazonensis and Leishmania braziliensis. One of the cationic Au I bis-N-heterocyclic carbenes (3) has low EC 50 values (ca. 4 μM) in promastigotes cells and no toxicity in host macrophages. Together with two other Au III complexes (6 and 7), the compound is also extremely effective in intracellular amastigotes from L. amazonensis. Initial mechanistic studies include an evaluation of the gold complexes' effect on L. amazonensis' plasma membrane integrity. Leishmaniasis is a vector-borne disease caused by Leishmania protozoan parasites that leads to cutaneous (localized, mucosal, diffuse, disseminated) or visceral manifestations, depending on the species, immune status of the host and geographic distribution. [1] Leishmania amazonensis and Leishmania braziliensis are important species related to cutaneous leishmaniasis in the New World, especially in Brazil, where about 73k to 120k people are infected every year. [2] While vaccines for humans are not available, antimony-based compounds, such as sodium stibogluconate (Pentostam®, Figure 1), amphotericin B (AMB), paromomycin, miltefosine, and pentamidine have been used for treating patients for several decades, despite their severe side effects and long-term parenteral administration in the majority of the cases. [3] In this context, a key area in [a

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Synthesis, characterization, and antileishmanial activity of neutral N-heterocyclic carbenes gold(I) complexes

Cited by 51 publications

References 37 publications

Cationic and Neutral N‐Heterocyclic Carbene Gold(I) Complexes: Cytotoxicity, NCI‐60 Screening, Cellular Uptake, Inhibition of Mammalian Thioredoxin Reductase, and Reactive Oxygen Species Formation

Cationic and Neutral N‐Heterocyclic Carbene Gold(I) Complexes: Cytotoxicity, NCI‐60 Screening, Cellular Uptake, Inhibition of Mammalian Thioredoxin Reductase, and Reactive Oxygen Species Formation

Antitrypanosomatid Pharmacomodulation at Position 3 of the 8‐Nitroquinolin‐2(1H)‐one Scaffold Using Palladium‐Catalysed Cross‐Coupling Reactions

Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

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