Chemodynamic therapy agents Cu(II) complexes of quinoline derivatives induced ER stress and mitochondria-mediated apoptosis in SK-OV-3 cells

Shen, Wangyang; Jia, Chun-Peng; Mo, Anna; Liang, Hong; Chen, Zhen-Feng

doi:10.1016/j.ejmech.2021.113636

Cited by 32 publications

(22 citation statements)

References 65 publications

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“…2-(2-Fluorophenyl)-3-aminoquinoline was synthesized according to the method described in previous reports. ,− 2-(2-Fluorophenyl)-3-aminoquinoline (238 mg, 1 mmol) and various 2-hydroxybenzaladehyde derivatives (1.1 mmol) were dissolved in CH 3 OH and stirred at 80 °C for 5–12 h, respectively. The H-L 1 –H-L 12 were obtained by cooling, filtering, and further recrystallization in CH 3 OH.…”

Section: Methodsmentioning

confidence: 99%

“…29−31 We recently reported that copper(II) complexes Cu1 and Cu2 with quinoline derivatives exert antitumor activity through CDT (Scheme 1A). 32 Although Cu1 and Cu2 displayed moderate antitumor activities, their relatively poor metabolic stabilities, excessive hydrophilicity, and other unsatisfactory pharmacokinetic profiles may limit their further development. There is a need to improve the drug-like properties of Cu1 and Cu2 derivatives.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The therapeutic efficacy of metal ions can be further enhanced when coordinated with biologically active alkaloid ligands. Our group has carried out extensive studies of metal complexes with bioactive alkaloids as ligands. − We recently reported that copper(II) complexes Cu1 and Cu2 with quinoline derivatives exert antitumor activity through CDT (Scheme A) …”

Section: Introductionmentioning

confidence: 99%

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Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

et al. 2022

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Twelve new complexes Cu(L1)2 –Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

et al. 2022

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“…Above results confirmed the ROS generation capability of Mn-ZnO 2 NPs in cancer cells via both endogenous (by Zn 2+ ) and exogenous (by H 2 O 2 ) avenues. Considering that DCFH-DA reacts with all ROS including H 2 O 2 and •OH [ 57 ], a novel live-cell permeant hydroxyl radical probe (MitoROS™ OH580) with a good selectivity toward •OH was used to evaluate the intracellular •OH level, which reacts with MitoROS™ OH580 to rapidly generate the red fluorescence [ 58 ]. Compared to negligible fluorescence in other groups (no treatment or ZnO 2 NPs), cells treated with MnCl 2 and H 2 O 2 did show red fluorescence, but still relatively weak ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS

Wang

Qu²,

Shao³

et al. 2023

Bioactive Materials

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“…Tetrahedrally distorted and square-planar copper(II) complexes with bidentate N , O -Schiff bases derived from substituted salicylaldehydes and 2-(2-fluorophenyl)-3-aminoquinoline showed remarkable cytotoxicity in a number of cancer cell lines in vitro and in vivo. This is due to their ability to generate reactive oxygen species (ROS) inducing mitochondrial disruption, caspase cascade activation, and ER stress, leading to sub-G1 cell cycle arrest and apoptosis . Five-coordinate copper(II)-bis(phenanthroline) complexes containing substituted imidazolidine-2-thione ligands induced ER stress and UPR in human ovarian A2780 cancer cells as confirmed by morphological TEM studies and Western blotting…”

Section: Introductionmentioning

confidence: 99%

Elucidation of Structure–Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action

et al. 2022

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Indolo[3,2- d ][1]benzazepines (paullones), indolo[3,2- d ][2]benzazepines, and indolo[2,3- d ][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2- d ][2]benzazepine-derived ligands HL 1 – HL 4 and copper(II) complexes 1 – 4 . All compounds were characterized by spectroscopic methods ( 1 H and 13 C NMR, UV–vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes 2 and 3 , in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by 1 H NMR and UV–vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure–activity relationships were deduced from the comparison of anticancer activities of HL 1 – HL 4 and 1 – 4 with those of structurally similar paullone-derived ( HL 5 – HL 7 and 5 – 7 ) and latonduine-derived scaffolds ( HL 8 – HL 11 and 8 – 11 ). The high anticancer activity of the lead drug candidate 4 was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.

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Chemodynamic therapy agents Cu(II) complexes of quinoline derivatives induced ER stress and mitochondria-mediated apoptosis in SK-OV-3 cells

Cited by 32 publications

References 65 publications

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS

Elucidation of Structure–Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action

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