Role of the NHE1 exchanger in the antitumor effects of copper(II) complexes and phenanthroline derivatives DOI Creative Commons
Katherine Seneth Muñoz Garzón,

Victor Martinez,

Verónica Celeste De Giusti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Abstract Three copper(II) complexes containing 1,10-phenanthroline ([CuCl 2 (phen)]·4H O, 1 ), neocuproine (neo)]·4H ) and tetramethyl-phenanthroline (tmp)]·4H 3 as the primary ligand another three with L-Ala-Phe dipeptide an auxiliary ligand: [Cu(L-Ala-Phe)(phen)]·4H O ( 4 [Cu(L-Ala-Phe)(neo)]·4H 5 [Cu(L-Ala-Phe)(tmp)]·4H 6 inhibited cell viability in breast cancer MCF-7 line, both monolayer spheroid culture models. The pair displayed a better selectivity index than cisPt non-cytotoxicity-related ROS induction apoptosis model. Cell proliferation was affected by all compounds concentration-dependent manner, more substantial effect on complexes. multicellular spheroids showed reduction from μM, IC 50 that were half one for cisplatin. All copper complexes, except DNA damage, demonstrated comet assay at concentration below . role of NHE1 has been linked to many types cancers. Our study revealed activity cells. However, only could extend their migration (Wound Healing Assay) MMP-9 studied zimography. Wester Blot analysis expressions MMP-2, MMP-9, when MCF7 cells treated six well. Overall, our results reveal antitumor fundamental migration.

Language: Английский

Isosteric Replacement of Sulfur to Selenium in a Thiosemicarbazone: Promotion of Zn(II) Complex Dissociation and Transmetalation to Augment Anticancer Efficacy DOI
Büşra Kaya,

Mahan Gholam Azad,

Mediha Süleymanoğlu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(14), P. 12155 - 12183

Published: July 5, 2024

We implemented isosteric replacement of sulfur to selenium in a novel thiosemicarbazone (PPTP4c4mT) create selenosemicarbazone (PPTP4c4mSe) that demonstrates potentiated anticancer efficacy and selectivity. Their design specifically incorporated cyclohexyl styryl moieties sterically inhibit the approach their Fe(III) complexes oxy-myoglobin heme plane. Importantly, contrast clinically trialed thiosemicarbazones Triapine, COTI-2, DpC, PPTP4c4mT PPTP4c4mSe did not induce detrimental oxidation. Furthermore, demonstrated more potent antiproliferative activity than homologous thiosemicarbazone, PPTP4c4mT, with selectivity being superior or similar, respectively, COTI-2. An advantageous property Zn(II) relative analogues was greater transmetalation Cu(II) lysosomes. This latter effect probably promoted activity. Both ligands down-regulated multiple key receptors display inter-receptor cooperation leads aggressive resistant breast cancer.

Language: Английский

Citations

7
Mechanisms of Copper-Induced Autophagy and Links with Human Diseases DOI Creative Commons
Yuanyuan Fu, Shuyan Zeng, Zhenlin Wang

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 99 - 99

Published: Jan. 15, 2025

As a structural and catalytic cofactor, copper is involved in many biological pathways required for the biochemistry of all living organisms. However, excess intracellular can induce cell death due to its potential catalyze generation reactive oxygen species, thus homeostasis strictly regulated. And deficiency or accumulation connected with various pathological conditions. Since success platinum-based compounds clinical treatment types neoplasias, metal-based drugs have shown encouraging perspectives drug development. Compared platinum, an essential trace element that may better prospects development than platinum. Recently, therapeutic role copper-induced autophagy chronic diseases such as Parkinson’s, Wilson’s, cardiovascular disease has already been demonstrated. In brief, ions, numerous complexes, copper-based nano-preparations could autophagy, lysosome-dependent process plays important human diseases. this review, we not only focus on current advances elucidating mechanisms compounds/preparations regulation but also outline association between

Language: Английский

Citations

0
The Role of Autophagy in Copper-Induced Apoptosis and Developmental Neurotoxicity in SH-SY5Y Cells DOI Creative Commons
Lu Lu, Ying Zhang, Wei Shi

et al.

Toxics, Journal Year: 2025, Volume and Issue: 13(1), P. 63 - 63

Published: Jan. 17, 2025

Copper (Cu) is a global environmental pollutant that poses serious threat to humans and ecosystems. induces developmental neurotoxicity, but the underlying molecular mechanisms are unknown. Neurons nonrenewable, they unable mitigate excessive accumulation of pathological proteins organelles in cells, which can be ameliorated by autophagic degradation. In this study, we established an vitro model Cu2+-exposed (0, 15, 30, 60 120 μM) SH-SY5Y cells explore role autophagy copper-induced neurotoxicity. The results showed copper resulted reduction shortening neural synapses differentiated cultured downregulated Wnt signaling pathway, nuclear translocation β-catenin. Exposure Cu2+ increased autophagosome flux blockage terms sequestosome 1 (p62/SQSTM1) microtubule-associated protein light chain 3B (LC3B) II/LC3BI expressions inhibition phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. Furthermore, induced apoptosis, characterized Bcl2 X (Bax), caspase 3, Poly (ADP-ribose) polymerase (PARP) decreased expression B-cell lymphoma 2 (Bcl2). Compared with μM exposure group alone, activator rapamycin pretreatment β-catenin translocation, LC3BII/LC3BI p62, as well upregulated 3 PARP. contrast, after inhibitor chloroquine pretreatment, were decreased, levels p62 upregulated, was while Bax, PARP increased. conclusion, study demonstrated associated neurotoxicity via might deepen understanding mechanism exposure.

Language: Английский

Citations

0
RECENT ADVANCES IN THE DISCOVERY OF COPPER(II) COMPLEXES AS POTENTIAL ANTICANCER DRUGS DOI Creative Commons
Bartłomiej Rogalewicz, Agnieszka Czylkowska

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 292, P. 117702 - 117702

Published: April 29, 2025

This review article offers a literature search of the most active, new copper (II) anticancer complexes based on nitrogen-containing ligands, reported in over past 5 years: from beginning 2019, until mid-2024. In modern world, cancer remains one deadliest diseases all. Although years ongoing research allowed us to better understand its nature, and thus aim more precisely at specific molecular targets pathways, many aspects remain unclear. Today, chemotherapy still forefront treatment. With ever-growing struggles overcome chemoresistance occurrence serious side effects, discovery new, selective active drugs is task an utmost importance. At same time, (II)-based compounds offer wide array biological activities valuable biochemical properties. provides update recent advances potential among five years.

Language: Английский

Citations

0
Mechanistic Insights of a p53-Targeting Small Molecule DOI
Ricardo J. Ferreira, Valentina Barcherini, Catarina Roma‐Rodrigues

et al.

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

Citations

0
Encapsulation of Cu(II) Terpyridine Complexes into Polymeric Nanoparticles for Enhanced Anticancer Therapy DOI Creative Commons
Nicolás Montesdeoca,

Kaixin Ni,

Johannes Karges

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(48)

Published: June 24, 2024

Cancer is one of the deadliest diseases worldwide. One most commonly applied therapeutic techniques to combat this disease chemotherapy. Despite its success, majority clinically chemotherapeutic agents are associated with strong side effects and drug resistance. To overcome limitation, much research efforts devoted toward development new anticancer agents. Among promising class compounds, Cu(II) complexes have emerged. their cytotoxic effect, these typically low water solubility, stability, poor tumor selectivity. limitations, herein, we report on encapsulation a terpyridine complex Pluronic F-127/Poloxamer-407 polymeric carrier into nanoparticles. Besides overcoming pharmacological drawbacks, nanoparticles were able eradicate human breast adenocarcinoma monolayer cells as well challenging multicellular spheroids at nanomolar concentrations.

Language: Английский

Citations

2
The Role of Intraligand Charge Transfer Processes in Iridium(III) Complexes with Morpholine-Decorated 4′-Phenyl-2,2′:6′,2″-terpyridine DOI Creative Commons
Joanna Palion‐Gazda,

Aleksandra Kwiecień,

Katarzyna Choroba

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3074 - 3074

Published: June 27, 2024

To investigate the impact of electron-donating morpholinyl (morph) group on ground- and excited-state properties two different types Ir(III) complexes, [IrCl3(R-C6H4-terpy-κ3N)] [Ir(R-C6H4-terpy-κ3N)2](PF6)3, compounds [IrCl3(morph-C6H4-terpy-κ3N)] (1A), 4[Ir(morph-C6H4-terpy-κ3N)2](PF6)3 (2A), [IrCl3(Ph-terpy-κ3N)] (1B) [Ir(Ph-terpy-κ3N)2](PF6)3 (2B) were obtained. Their photophysical comprehensively investigated with aid static time-resolved spectroscopic methods accompanied by theoretical DFT/TD-DFT calculations. In case bis-terpyridyl iridium(III) attachment induced dramatic changes in absorption emission characteristics, manifested appearance a new, very strong visible tailing up to 600 nm, significant bathochromic shift 2A relative model chromophore. The features 2B found originate from triplet excited states natures: intraligand charge transfer (3ILCT) for small admixture metal-to-ligand (3IL–3MLCT) 2B. optical mono-terpyridyl complexes less significantly impacted substituent. Based UV–Vis spectra, wavelengths lifetimes environments, transient studies, calculations, it was demonstrated that 1A are governed singlet mixed MLLCT-ILCT nature, dominant contribution first component, is, metal-ligand-to-ligand (MLLCT). involvement ILCT transitions reflected an enhancement molar extinction coefficients bands range 350–550 red its

Language: Английский

Citations

2
Advancement in schiff base complexes for treatment of colon cancer DOI
Afaf Murtadha Kadhum,

Shaimaa Hassan Mallah,

Azal Shakir Waheeb

et al.

Reviews in Inorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract Schiff bases have proven to be beneficial in medicine and interesting complexation capabilities with transition metals. The +4, +5, +6 oxidation states of schiff base metal complexes been the subject recent review, which highlighted their notable cytotoxic effects against various colon cancer cell lines (HT-29, HCT-116, SW-480, Coco-2, CT-26, LT-174, LoVo). Extensive research has focused on +4 states, exhibiting distinct geometries significant thermodynamic stability. These studies provide IC 50 values for these along comprehensive structural representations that shed light how different substituents affect cytotoxicity. When compared ligands alone, shown significantly reduce invasion proliferation. studied literature emphasizes complexe’s potential biological applications suggests more study may necessary fully comprehend biology. To enable sophisticated multidisciplinary this field, future investigations should focus synthesizing novel enhanced bioavailability, solubility, low toxicity.

Language: Английский

Citations

2
Synthesis, X-ray Studies and Photophysical Properties of Iridium(III) Complexes Incorporating Functionalized 2,2′:6′,2″ Terpyridines and 2,6-Bis(thiazol-2-yl)pyridines DOI Creative Commons
Bartosz Zowiślok, Anna Świtlicka, Anna Maroń

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(11), P. 2496 - 2496

Published: May 24, 2024

A series of iridium(III) triimine complexes incorporating 2,2′:6′,2″-terpyridine (terpy) and 2,6-bis(thiazol-2-yl)pyridine (dtpy) derivatives were successfully designed synthesized to investigate the impact peripheral rings (pyridine, thiazole) substituents (thiophene, bithiophene, EDOT) attached skeleton on their photophysical properties. The Ir(III) fully characterized using IR, 1H, elemental analysis single crystal X-ray analysis. Their thermal properties evaluated TGA measurements. Photoluminescence spectra [IrCl3L1–6] investigated in solution at 298 77 K. experimental studies accompanied by DFT/TDDFT calculations. ligands studied detail electronic absorption emission. In solution, they exhibited photoluminescence quantum yields ranging from 1.27% 5.30% depending chemical structure. research included conducted emission techniques. displayed

Language: Английский

Citations

0
Strong in vitro anticancer activity of copper(II) and zinc(II) complexes containing naturally occurring Lapachol: Cellular effects in ovarian A2780 cells DOI Creative Commons
Sara Stocchetti, Ján Vančo, Jan Belza

et al.

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Heteroleptic Cu( ii ) and Zn( complexes (1–7) of lapachol revealed strong anticancer effects on a panel six human cancer cells lowered toxicity in normal MRC-5 cells. Cellular A2780 uncovered possible mechanism action.

Language: Английский

Citations

0