Notwithstanding progress in chemotherapy, cancer recurrence resulting from metastasis continues to be a significant challenge. Consequently, targeting the epithelial–mesenchymal transition (EMT) has emerged as a viable approach to impede metastasis and enhance therapy success. In colorectal cancer, current initiatives focus on discovering new agents that are both efficacious and less harmful to normal cells. Plant-derived flavonoids and metal-based compounds exhibit significant medicinal potential. This research examined the anticancer efficacy of a Cu(II)-flavonoid complex comprising quercetin and 1,10-phenanthroline ligands in colorectal cancer cell lines HCT-116 and HT-29. The sulforhodamine B (SRB) assay assessed cell viability, yielding IC₅₀ values of 3.19 μM for HCT-116 and 1.81 μM for HT-29 after 48 h, but the individual ligands demonstrated no similar cytotoxicity. The compound exhibited lower cytotoxicity to normal colon cells (CCD-18Co) than toward colorectal cancer cells (HCT-116 and HT-29). Apoptosis induction was verified with Hoechst 33342, Annexin-V-FITC, and propidium Iodide staining, supplemented by M30-antigen ELISA, and further corroborated by the pan-caspase inhibitor Z-VAD-FMK and elevated levels of apoptotic protein markers such as cleaved caspase-8 and parp-1. Flow cytometry revealed G₀/G₁ phase arrest, indicating caspase-dependent apoptotic cell death. The compound also impeded epithelial-mesenchymal transition, as demonstrated by a dose-dependent reduction in migration and invasion in wound healing and Matrigel invasion experiments. Western blot analysis revealed elevated levels of E-cadherin and reduced levels of N-cadherin, vimentin, and snail. The Cu(II)-flavonoid combination demonstrates significant anti-proliferative, pro-apoptotic, and anti-metastatic properties in colorectal cancer cells, while exhibiting lower cytotoxic effects in normal colon cells. This underscores its potential as a viable candidate for additional molecular and in vivo assessment of the complex in colorectal cancer.

Bu çalışmada 5,7-dihidroksiflavon (chrysin, chr) ve 4,4′-di-ter-bütil-2,2′-bipiridin (4,4’-dtbbpy) ligandları kullanılarak Cu(II) iyonunun yeni bir karışık ligand-bakır(II) koordinasyon bileşiği elde edildi. Sentezlenen bu koordinasyon bileşiğinin yapısı, elementel analiz, iletkenlik, manyetik süsseptibilite, kütle spektrometrisi ve Infrared (IR) spektroskopisi yöntemleriyle aydınlatıldı. Ayrıca TGA/DSC analizi ile yapısı desteklendi ve termal özellikleri araştırıldı. Elde edilen analiz verilerinden sentezlenen bileşikte, Cu(II) iyonu:chr-H:4,4’-dtbbpy oranının 1:1:1 olduğu ve koordinasyon küresi içerisinde ClO4- iyonunun bulunduğu nötral bir kompleks elde edildiği saptandı. Sonuç olarak sentezlenen koordinasyon bileşiği için [Cu(chr-H)(ClO4)(4,4’-dtbbpy)] formülü önerildi.

This article covers the anticancer activities and mechanisms of action of Cu(II) complexes of flavonoid-derived quercetin and 1,10-phenanthroline ligands. The antiproliferative activity of the complex and its ligands was evaluated by MTT, ATP, and SRB viability assays in human lung cancer cells (A549, H1299). Findings for apoptosis were determined by fluorescent staining, flow cytometry analysis, and the M30 antigen method. In addition, the mechanism of action of the complex was investigated by Annexin V staining, caspase 3/7 activity, ROS formation, and cell cycle analysis. The involvement of caspases, thus, apoptosis was confirmed by rescuing cell death by using a pan-caspase inhibitor (Z-VAD-FMK). Again, increased ROS levels in the cell showed that death may occur by apoptosis. For this reason, the accuracy of ROS-induced apoptosis in cells has been proven as a result of the application of N-acetylcysteine (NAC), which is a ROS inhibitor. The efficacy of the complex was compared with Cisplatin and ligands. The results showed that the Cu(II) flavonoid complex is cytotoxic on lung cancer cells and may have the potential to act as an effective metal-based anticancer drug with a lower IC50 over Cisplatin.

In this study, the new heteroleptic Cu(II) complexes of chrysin were synthesized by using 2,2 -bipyridine and substituted 1,10-phenanthroline (1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline or bathophenanthroline) co-ligands. The characterization of the obtained heteroleptic Cu(II) complexes were carried out by elemental analysis, ESI-MS, UV-visible and infrared spectral analyses, thermal analysis, magnetic susceptibility and molar conductivity measurements. In these complexes, chrysin, 2,2 - bipyridine, or substituted 1,10-phenanthrolines and Cu(II) ion were found in a ratio of 1: 1: 1. In addition, the resulting data supported square plane geometry for Cu(II) complexes. According to the results obtained, the proposed compositions are as follows: [Cu(chrH-1)(bPY)]ClO4 center dot H2O (1, chrH = chrysin, bpy = 2,2'-bipyridine), [Cu(chrH-1)(phen)]ClO4 center dot 1.5H(2)O (2, phen = 1,10 - phenanthroline), [Cu(chrH-1)(dmphen)]ClO4 (3, dmphen = 4,7-dimethyl-1,10-phenanthroline) and [Cu(chrH-1)(Bphen)]ClO4 (4, Bphen = Bathophenanthroline). Total phenolic contents and antioxidant capacities of Complexes 1-4 were measured by the Folin-Ciocalteu and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) methods, respectively. According to the results, Complex 4 has the highest antioxidant capacity. (C) 2020 Elsevier B.V. All rights reserved.

Flavonoids are natural products which are known to have biological activity for human health. In this study, new mixed ligand complexes of Ni(II) and Cu(II) were synthesized by using flavonoid (quercetin or naringenin) and heterocyclic imine (2,2′:6′,2′′-terpyridine or 2,2ꞌ-bipyiridine) ligands. The new complexes are [Ni(narH-1)(terpy)Cl].4H2O (1, nar = naringenin, terpy = 2,2′:6′,2′′-terpyridine), [Cu(narH-1)(terpy)Cl].H2O (2), and [Cu(queH-1)(bpy)(O3N)].1.5H2O (3, que = quercetin, bpy = 2,2ꞌ-bipyiridine). The structural features of the synthesized mixed ligand complexes were investigated using elemental analysis, thermogravimetric analysis, Fourier transform infrared spectroscopy, magnetic susceptibility and molar conductivity measurements. The resulting data demonstrated an octahedral geometry for Complex 1 and Complex 2 and square pyramidal geometry for Complex 3. Antioxidant capacity and total phenolic content of Complexes 1–3 were measured by the Folin-Ciocalteu and ABTS methods. Antiproliferative effect of complexes were tested by SRB and ATP assays on MCF-7 (breast cancer), A549 (nonsmall cell lung cancer), PC-3 (prostate cancer) and HeLa (human cervical cancer) cell lines. Apoptosis was identified using by the fluorescence imaging, caspase cleaved cytokeratin-18 and flow cytometry analysis. Complex 2 and 3 had high total phenolic content and antioxidant activity. Complex 2 was found to show selective cytotoxicity through the induction of apoptosis on MCF-7 cells with having a very low IC50 value (<0.8 μM; the half maximum inhibitory concentration) while its ligands showed much higher cytotoxicity (IC50 > 50 μM). In conclusion, Complex 2 is a highly promising and novel compound for breast cancer and warrants further animal experiments.

In this work, mixed ligand complexes of Co(II) Ni(II) and Cu(II) were synthesized using quercetin and diimine (1,10-phenanthroline or 2,2′-bipyiridine) ligands. The obtained Ni(II) and Co(II) complexes are new and the Cu(II) complexes are synthesized by different method from the literature. The characterization of complexes was performed by elemental analysis, thermogravimetric analysis, ESI–MS, UV–visible and infrared spectral analyses, magnetic susceptibility and molar conductivity measurements. It was found that quercetin, diimine and metal(II) ion form 1:1:1 complexes. Resulting data supported octahedral geometry for Ni(II) and Co(II) complexes and square pyramidal geometry for Cu(II) complexes. The proposed compositions are [Co(queH-1)Cl(phen)(H2O)]∙2H2O (1, queH = quercetin, phen = 1,10-phenanthroline), [Ni(queH-1)Cl(phen)(H2O)]∙2H2O (2), [Cu(queH-1)Cl(phen)]∙2.5H2O (3) and [Cu(queH-1)Cl(bpy)]∙2H2O (4, bpy = 2,2′-bipyiridine). Antioxidant capacity and total phenolic content of complexes measured by Folin–Ciocalteu and ABTS methods. Anti-cancer effect of these compounds were tested against different cancer cells (A549, PC-3, HeLa and MCF-7). Apoptosis identified by the fluorescence imaging, caspase cleaved cytokeratin-18 and flow cytometry analysis (annexin V, caspase 3/7, mitochondria membrane potential and oxidative stress). As a result, Cu(II) complexes are more effective than the other compounds and Complex 3 is a promising anti-cancer compound against breast cancer MCF-7 and MDA-MB-231 cells (IC50 values are 2.4 and 5.4 µM for 48 h, respectively). Flow cytometry analysis exhibited that Complex 3 caused apoptosis in MCF-7 cells. These results support that Complex 3 has anticancer activity and can be a potential anticancer agent especially in breast cancer.

Bu çalışmada, Na(sac) (sac: sakkarinat) varlığında kobalt(II) klorür ile 1-(2-etil-1,2,3,4-tetrahidro-kinazolin-2-il)-etanon oksimin (HL) tepkimesinden [Co(HL ' ) 2 ](sac) · H 2 O kompleksi elde edildi. Bu yeni kompleksin yapısal aydınlatması elementel analiz, spektroskopik yöntemler (UV-Vis., FT-IR, 1 H-NMR, 13 C-NMR ve LC-MS) ve teermal analiz yöntemleri (TG-DTA) ile gerçekleştirildi. Elde edilen sonuçlar kompleks oluşumu sırasında ligandın halka açılma tepkimesine uğradığını ve zincir tautomerinin bir N,N,N-verici olarak davrandığını göstermektedir. Co(III) iyonu ile iki HL ' ligandının koordinasyonundan oluşan bu katyonik komplekste, sac anyonu tamamlayıcı iyon olarak koordinasyon küresinin dışında yer almaktadır.

Binary and ternary water soluble copper(II) complexes - [Cu(nphen)2(H2O)](NO3)2·H2O (1), [Cu(phen)2(H2O)](NO3)2 (2), [Cu(nphen)(l-tyr)(H2O)]NO3·2H2O (3), [Cu(phen)(tyr)(H2O)] NO3·2H2O (4) - and diquarternary salts of nphen and phen (nphen=5-nitro-1,10-phenanthroline, phen=1,10-phenanthroline and tyr=l-tyrosine) have been synthesized and characterized by CHN analysis, (1)H NMR, (13)C NMR and IR spectroscopy, thermal analysis and single crystal X-ray diffraction techniques. The CT-DNA binding properties of these compounds have been investigated by thermal denaturation measurements, absorption and emission spectroscopy. The supercoiled pUC19 plasmid DNA cleavage activity of these compounds has been explored by agarose gel electrophoresis. The cytotoxicity of these compounds against MCF-7, Caco-2, A549 cancer cells and BEAS-2B healthy cells was also studied by using XTT method. The complexes 1-4 exhibit significant high cytotoxicity with low IC50 values in compared with cisplatin. The effect of the substituents of phen and coordinated amino acid in the above complexes are presented and discussed.

Two new water-soluble copper(II) complexes, [Cu(dmphen)2(NO3)]NO3 (1), [Cu(dmphen)(tyr)(H2O)]NO3·H2O (2) and the diquarternary salt of dmphen (dmphen = 4,7-dimethyl-1,10-phenanthroline and tyr = l-tyrosine), have been synthesized and characterized by elemental analysis, 1H NMR, 13C NMR and IR spectroscopy, thermal analysis and single crystal X-ray diffraction techniques. The CT-DNA binding properties of these compounds have been investigated by absorption, emission spectroscopy and thermal denaturation measurements. The supercoiled pBR322 plasmid DNA cleavage activity of these compounds has been explored by agarose gel electrophoresis. The cytotoxicity of these compounds against MCF-7, Caco-2, A549 cancer cells and BEAS-2B healthy cells was also studied by the XTT method. Complexes 1 and 2 exhibit significant cytotoxicity, with lower IC50 values than those of cisplatin.

1-(2-ethyl-1,2,3,4-tetrahydro-quinazolin-2-yl)-ethanone oxime (ETQX, HL) and the Cu(II) complex of its open-chain tautomer were synthesised and characterised by elemental analysis, magnetic susceptibility, molar conductance, thermal analyses, and spectral (IR, NMR, AAS, LC-MS, and UV-Vis) studies. The accumulated data exhibited that the ligand underwent a ring-opening reaction upon formation of a mononuclear Cu(II) complex in which the chain tautomer acted as an N,N,N-donor. The Cu(II) complex was formed in a 1 : 1 (M : HL′) ratio, as indicated by analytical results and the general formula was elucidated to be [Cu(HL′)Cl]Cl. The protonation constants of ETQX and the stability constants of the complex species formed with the Cu(II) of ETQX were studied by the potentiometric method at 25°C in 0.1 M KCl ionic medium. A complexation model for the Cu(II)-ETQX system was established with the software program “BEST” based on the potentiometric data. The concentration distribution curves of ETQX and Cu(II)-ETQX complex species in solution were evaluated by the SPE software program. The stoichiometry of the Cu(II) complex in solution was observed to be similar to that of the solid state Cu(II) complex.

In this study, new heterocyclic ligands, 2-(3-chloro-phenyl)-1,2,3,4-tetrahydro-quinazoline-2-carbaldehyde oxime,(HL1) and 2-(3-bromo-phenyl)-1,2,3,4-tetrahydro-quinazoline-2-carbaldehy- de oxime,(HL2), and Co(III) complexes of their open-chain tautomer,(HL1′ and HL2′), containing oxime, imine, and amine donor groups resulting from the reactions with Co(II) ion have been synthesized and characterized by spectral methods, elemental analysis, magnetic susceptibility, and thermal analysis (TG, DTG, and DTA) techniques. The obtained results show that the ligands undergo a ring-opening reaction upon complexation with Co(III) ion. The analyses confirmed the following molecular formulae: [Co(L1′)2]Cl.H2O and [Co(L2′)2]Cl.H2O.

A new ligand, 2−(p−tolyl)−1,2,3,4−tetrahydroquinazoline−2 −carbaldehyde oxime, was synthesized from a condensation reaction of oxo−p−tolyl−acetaldehyde oxime with 2−aminobenzyl- amine and then amine−imine−oxime complexes of this compound that formed with Co(III) and Ni(II) ions were obtained. All structures were characterized by spectral methods, elemental analysis, magnetic susceptibility, molar conductivity, and thermal analyses. The results that were obtained show that the cyclic ligand, HL, undergoes a ring−opening reaction upon complexation with metal ions. The Co(III) and Ni(II) complexes have a metal−ligand ratio of 1:2 and the imine ligand coordinates through the amine, imine, and oxime groups nitrogen atoms with metal ions.

A new ligand, 2(ptolyl)1,2,3,4tetrahydroquinazoline2 carbaldehyde oxime, was synthesized from a condensation reaction of oxoptolylacetaldehyde oxime with 2aminobenzyl- amine and then amineimineoxime complexes of this compound that formed with Co(III) and Ni(II) ions were obtained. All structures were characterized by spectral methods, elemental analysis, magnetic susceptibility, molar conductivity, and thermal analyses. The results that were obtained show that the cyclic ligand, HL, undergoes a ringopening reaction upon complexation with metal ions. The Co(III) and Ni(II) complexes have a metalligand ratio of 1:2 and the imine ligand coordinates through the amine, imine, and oxime groups nitrogen atoms with metal ions.

A novel 1,2,3,4-tetrahydroquinazoline oxime was synthesised from a condensation reaction of 2-(naphthalen-2-yl)-2-oxoacetaldehyde oxime with 2-aminobenzylamine. Subsequently, a-imine oxime complexes of this compound that formed with Co(III) and Ni(II) metal ions were obtained. All structures were characterised by spectral methods (FT-IR, nmr, AAS, mass), elemental analysis, thermal analyses, magnetic susceptibility and molar conductivity. The analyses confirmed the following molecular formulae: [Co(L)2]Cl • C2H5OH • 0,5H2O and [Ni(HL)2]Cl2. The Co(III) complex is diamagnetic. Magnetic susceptibility measurements revealed octahedral geometry for the Co(III) and Ni(II) complexes. In the complexes, the chloride ion was found to be noncoordinated to the metal ions as confirmed by conductivity measurements. The NMR spectra of the Co(III) complex confirmed the presence ofethanol in the Co(III) complex. The experimental results of TG-DTA showed that the Co(III) complex contained ethanol and crystal water in the first two stages. The end of the thermal decomposition of the complexes yielded a final product of a metal oxide.