Development of ESI-MS-based continuous enzymatic assay for real-time monitoring of enzymatic reactions of acetylcholinesterase

Fu, Qiang; Tang, Jun; Cui, Meng; Zheng, Zhong; Liu, Zhi‐Qiang; Liu, Shuying

doi:10.1016/j.jchromb.2015.03.022

Cited by 9 publications

(7 citation statements)

References 34 publications

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“…They can be hydrolyzed selectively or nonselectively by a variety of esterases to release active pharmacophores . The responses of 1 a – 3 a to esterase were monitored by fluorescence spectroscopy, time‐resolved emission spectroscopy, and ESI‐MS . Herein, porcine liver esterase (PLE) was used as a model to investigate the hydrolytic process of the ester bonds in 1 a – 3 a .…”

Section: Resultsmentioning

confidence: 99%

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Chen

Tan

et al. 2017

Chemistry A European J

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Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. Phosphorescent cyclometalated Ir complexes have emerged as potential anticancer agents. By conjugation of VPA to Ir complexes through an ester bond, VPA-functionalized cyclometalated iridium(III) complexes 1 a-3 a were designed and synthesized. These complexes display excellent two-photon properties, which are favorable for live-cell imaging. The ester bonds in 1 a-3 a can be hydrolyzed quickly by esterase and display similar inhibition of HDAC activity to VPA. Notably, 1 a-3 a can overcome cisplatin resistance effectively and are about 54.5-89.7 times more cytotoxic than cisplatin against cisplatin-resistant human lung carcinoma (A549R) cells. Mechanistic studies indicate that 1 a-3 a can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, accumulate in mitochondria, and induce a series of cell-death-related events mediated by mitochondria. This study gives insights into the design and anticancer mechanisms of multifunctional anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Chen

Tan

et al. 2017

Chemistry A European J

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“…The hydrolysis of ten Ir(III) complexes by PLE were detected by ESI-MS (Supplementary Fig. S14)28. Equal amounts of Ir(III) complexes (20 μM, 100 μL) were incubated with PLE (0.6 units) in Tris-HCl solution (10 mM, pH 7.4) for 2 h. The mass spectra peaks of 1a ( m/z 745) or 1b ( m/z 817) remain unchanged.…”

Section: Resultsmentioning

confidence: 99%

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

Wang

Chen

et al. 2016

Sci Rep

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Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.

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“…1 Monitoring the reaction time course under such conditions provides kinetic and structural information on the reagents, intermediates, and nal products, improving the understanding of reaction mechanisms and kinetic properties. 2 Common spectroscopic methods used for this purpose include midinfrared (MIR), 3 Raman, 4 near-infrared (NIR), 5 mass (MS) 2,6 and nuclear magnetic resonance (NMR) [7][8][9][10][11][12] spectroscopies.…”

Section: Introductionmentioning

confidence: 99%

¹H and ¹⁹F NMR in drug stress testing: the case of voriconazole

et al. 2017

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Development of ESI-MS-based continuous enzymatic assay for real-time monitoring of enzymatic reactions of acetylcholinesterase

Cited by 9 publications

References 34 publications

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

¹H and ¹⁹F NMR in drug stress testing: the case of voriconazole

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Development of ESI-MS-based continuous enzymatic assay for real-time monitoring of enzymatic reactions of acetylcholinesterase

Cited by 9 publications

References 34 publications

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Valproic Acid‐Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria‐Targeting Anticancer Agents

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

1H and 19F NMR in drug stress testing: the case of voriconazole

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¹H and ¹⁹F NMR in drug stress testing: the case of voriconazole