Apoptosis Induction in HepG2 and HCT116 Cells by a Novel Quercetin-Zinc (II) Complex: Enhanced Absorption of Quercetin and Zinc (II).

Quercetin forms complexes with various metals due to its structural attributes. It predominantly exhibits chelating activity at the 3-hydroxy/4-carbonyl group. Previously, coordination in synthetically obtained quercetin-zinc (II) complexes has been limited to this group. However, the expanded coordination observed in quercetin-iron complexes has opened avenues for diverse applications. Thus, synthesizing novel quercetin-zinc complexes with different coordination positions is a significant advance. In our study, we not only synthesized and comprehensively characterized a new quercetin-zinc (II) complex, Zn-Q, but also evaluated the structure and bioactivity of chelate complexes (Q+Zn) derived from co-treatment in cell culture mediums. The structure of the new compound Zn-Q was comprehensively characterized using 1D 1H and 2D correlation spectroscopy (COSY), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometer (ESI-MS), and X-ray diffraction analysis (XRD) analysis. Subcellular localization and absorption of these zinc (II) complexes were determined using the ZnAF-2 DA zinc ion fluorescence probe. Throughout the experiments, both Zn-Q and Q+Zn exhibited significant antioxidant, cell growth inhibitory, and anticancer effects in HepG2 and HCT116 cells, with Zn-Q showing the highest potential for inducing apoptosis via the caspase pathway. Tracking intracellular zinc complex absorption using zinc fluorescent probes revealed zinc (II) localization around the cell nucleus. Interestingly, there was a proportional increase in intracellular quercetin absorption in conjunction with zinc (II) uptake. Our research highlights the advantages of quercetin complexation with zinc (II): enhanced anticancer efficacy compared to the parent compound and improved bioavailability of both quercetin and zinc (II). Notably, our findings, which include enhanced intracellular uptake of both quercetin and zinc (II) upon complex formation and its implications in apoptosis, contribute significantly to the understanding of metal-polyphenol complexes. Moving forward, comprehensive functional assessments and insights into its mechanism of action, supported by animal studies, are anticipated.

Synthesis, Structure, Spectral-Luminescent Properties, and Biological Activity of Chlorine-Substituted N-[2-(Phenyliminomethyl)phenyl]-4-methylbenzenesulfamide and Their Zinc(II) Complexes.

New azomethine compounds of 2-(N-tosylamino)benzaldehyde or 5-chloro-2-(N-tosylamino)benzaldehyde and the corresponding chlorine-substituted anilines, zinc(II) complexes based on them have been synthesized. The structures of azomethines and their complexes were determined by elemental analysis, IR, 1H NMR, X-ray spectroscopy, and X-ray diffraction. It is found that all ZnL2 complexes have a tetrahedral structure according to XAFS and X-ray diffraction data. The photoluminescent properties of azomethines and zinc complexes in methylene chloride solution and in solid form have been studied. It is shown that the photoluminescence quantum yields of solid samples of the complexes are an order of magnitude higher compared to the solutions and range from 11.34% to 48.3%. The thermal properties of Zn(II) complexes were determined by thermal gravimetric analysis (TGA) and differential scanning calorimetry. The TGA curves of all the compounds suggest their high thermal stability up to temperatures higher than 290 °C. The electrochemical properties of all complexes were investigated by the cyclic voltammetry method. The multilayered devices ITO/PEDOT:PSS/NPD/Zn complex/ TPBI/LiF/Al with wide electroluminescence (EL) color range spanning the range from bluish-green (494 nm) to green (533 nm) and the high values of brightness, current and power efficiency were fabricated. The biological activity of azomethines and zinc complexes has been studied. In the case of complexes, the protistocidal activity of the zinc complex with azomethine of 5-chloro-2-(N-tosylamino)benzaldehyde with 4-chloroaniline was two times higher than the activity of the reference drug toltrazuril.

Zinc(II) Complexes of Amino Acids as New Active Ingredients for Anti-Acne Dermatological Preparations.

Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc-amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability.

Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents.

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.

Zinc(II) Complexes with Amino Acids for Potential Use in Dermatology: Synthesis, Crystal Structures, and Antibacterial Activity.

The multifunctional profile of Zn2+ has influenced its great popularity in various pharmaceutical, food, and cosmetic products. Despite the use of different inorganic and organic zinc derivatives, the search for new zinc-containing compounds with a safer skin profile still remains an open issue. The present paper describes the synthesis, structural characterization, and antibacterial activity of zinc(II) complexes with proteinogenic amino acids as potential candidates for dermatological treatments. The obtained complexes are of the general formula [Zn(AA)2], where AA represents an amino acid (L-Glu, Gly, L-His, L-Pro, L-Met, and L-Trp). Their synthesis was designed in such a way that the final bis(aminoacidate) zinc(II) complexes did not contain any counter-ions such as Cl-, NO3-, or SO42- that can cause some skin irritations. The chemical structure and composition of the compounds were identified by 1H NMR spectroscopy and elemental analysis, and four were also characterized by single-crystal X-ray diffraction. The Hirshfeld surface analysis for the Zn2+ metallic center helped to determine its coordination number and geometry for each complex. Finally, the antibacterial properties of the complexes were determined with respect to three Gram-positive strains, viz. Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Streptococcus pyogenes ATCC 19615, and two Gram-negative bacteria, viz. Escherichia coli ATCC 25992 and Pseudomonas aeruginosa ATCC 27853, and were compared with the activity of zinc 2-pirrolidone 5-carboxylate (ZnPCA), commonly applied in dermatology. It was found that the Zn(II) complexes with methionine and glycine exhibited a higher antibacterial activity than the tested standard, and the antimicrobial properties of complex with Trp were satisfactory. The results of the antimicrobial activity examination allow us to postulate that the obtained zinc complexes might become new active substances for use in dermatological products.

Synthesis, Characterization, Photoluminescence, Molecular Docking and Bioactivity of Zinc (II) Compounds Based on Different Substituents.

Six new zinc(II) complexes were prepared by the reaction of ZnBr2 or ZnI2 with 4'-(substituted-phenyl)-2,2':6',2''-terpyridine compounds, bearing p-methylsulfonyl (L1), p-methoxy (L2) and p-methyl (L3), which were characterized by elemental analysis, FT-IR, NMR and single crystal X-ray diffraction. The antiproliferative properties against Eca-109, A549 and Bel-7402 cell lines and the cytotoxicity test on RAW-264.7 of these compounds were monitored using a CCK-8 assay, and the studies indicate that the complexes show higher antiproliferative activities than cisplatin. The interactions of these complexes with CT-DNA and proteins (BSA) were studied by UV-Vis, circular dichroism (CD) and fluorescent spectroscopy, respectively. The results indicate that the interaction of these zinc(II) complexes with CT-DNA is achieved through intercalative binding, and their strong binding affinity to BSA is fulfilled through a static quenching mechanism. The simulation of the complexes with the CT-DNA fragment and BSA was studied by using molecular docking software. It further validates that the complexes interact with DNA through intercalative binding mode and that they have a strong interaction with BSA.

On the Aggregation and Sensing Properties of Zinc(II) Schiff-Base Complexes of Salen-Type Ligands.

The zinc(II) ion forms stable complexes with a wide variety of ligands, but those related to Schiff-bases are among the most largely investigated. This review deals with the peculiar aggregation characteristics of Zn(II) Schiff-base complexes from tetradentate N2O2 salen-type ligands, L, derivatives from salicylaldehydes and 1,2-diamines, and is mostly focused on their spectroscopic properties in solution. Thanks to their Lewis acidic character, ZnL complexes show interesting structural, nanostructural, and aggregation/deaggregation properties in relation to the absence/presence of a Lewis base. Deaggregation of these complexes is accompanied by relevant changes of their spectroscopic properties that can appropriately be exploited for sensing Lewis bases. Thus, ZnL complexes have been investigated as chromogenic and fluorogenic chemosensors of charged and neutral Lewis bases, including cell imaging, and have shown to be selective and sensitive to the Lewis basicity of the involved species. From these studies emerges that these popular, Lewis acidic bis(salicylaldiminato)Zn(II) Schiff-base complexes represent classical coordination compounds for modern applications.

Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies.

Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (Zn(II)) thiosemicarbazone complexes [Zn(atc-Et)2] (1) and [Zn(atc-Ph)2] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (¹H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research.

Influence of Solvation and Structural Contributions on Fluorescence of Dipyrrine Dyes.

The results of quantum-chemical and spectral researches of zinc((II)) complexes with alkylated dipyrrine and 3,3'-, 2,3'- and 2,2'-bis(dipyrrine)s in non-polar and polar solvents and their binary mixtures are presented. It was investigated the efficiency of the fluorescence quenching of fluorophores depending on of the solvation and structural contributions. Found that 3,3'-bis(dipyrrinato)zinc((II)) demonstrates the highest sensitivity of the fluorescence to the presence of the electron-donor component compared with the studied complexes. The obtained results allow to offer dipyrrine and bis(dipyrrine) zinc((II)) complexes as new, highly sensitive and selective fluorescent sensors of the N- and O-containing toxicants. Graphical Abstract Influence of solvation and structural contributions on fluorescence of dipyrrine dyes.

Modification of extended open frameworks with fluorescent tags for sensing explosives: competition between size selectivity and electron deficiency.

Three new electron-rich metal-organic frameworks (MOF-1-MOF-3) have been synthesized by employing ligands bearing aromatic tags. The key role of the chosen aromatic tags is to enhance the π-electron density of the luminescent MOFs. Single-crystal X-ray structures have revealed that these MOFs form three-dimensional porous networks with the aromatic tags projecting inwardly into the pores. These highly luminescent electron-rich MOFs have been successfully utilized for the detection of explosive nitroaromatic compounds (NACs) on the basis of fluorescence quenching. Although all of the prepared MOFs can serve as sensors for NACs, MOF-1 and MOF-2 exhibit superior sensitivity towards 4-nitrotoluene (4-NT) and 2,4-dinitrotoluene (DNT) compared to 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitrobenzene (TNB). MOF-3, on the other hand, shows an order of sensitivity in accordance with the electron deficiencies of the substrates. To understand such anomalous behavior, we have thoroughly analyzed both the steady-state and time-resolved fluorescence quenching associated with these interactions. Determination of static Stern-Volmer constants (KS) as well as collisional constants (KC) has revealed that MOF-1 and MOF-2 have higher KS values with 4-NT than with TNT, whereas for MOF-3 the reverse order is observed. This apparently anomalous phenomenon was well corroborated by theoretical calculations. Moreover, recyclability and sensitivity studies have revealed that these MOFs can be reused several times and that their sensitivities towards TNT solution are at the parts per billion (ppb) level.

Zinc Complexes of Fluorosubstituted N-[2-(Phenyliminomethyl)phenyl]-4-methylbenzenesulfamides: Synthesis, Structure, Luminescent Properties, and Biological Activity.

Mono-, di-, and trifluorophenyl substituted in different positions of amine fragments bis [2-[[(E)-((fluorophenyl)iminomethyl]-N-(p-tolylsulfonyl)anilino]zinc(II) complexes were synthesized. Their crystal structure, photo- and electroluminescent properties, and protistocidal, fungistatic, and antibacterial activities were studied. It has been shown that the introduction of fluorine atoms and an increase in their number in the ligand structure of the resulting metal complexes promote the luminescence quantum yields and values of performance and brightness in EL cells compared to their previously studied chlorine-substituted analogs.

Di-µ-adipato-κ4 O 1,O 1':O 6,O 6'-bis-[(2,2'-di-pyridyl-amine-κ2 N,N')zinc(II)] trihydrate.

The title compound, [Zn2(C6H8O4)2(C10H9N3)2]·3H2O or {Zn2[(C5H4N)2NH]2[µ-(CH2)4(COO)2]2}·3H2O, was separ-ated from the solvothermal reaction of zinc(II) sulfate hepta-hydrate, 2,2'-di-pyridyl-amine and sodium adipate. The dinuclear metal complex has a centrosymmetric structure, with the ZnII atom adopting a highly distorted octa-hedral coordination sphere composed of four oxygen atoms from bridging adipato ligands and two pyridine nitro-gen atoms. In the crystal, the title compound aggregates into a tri-periodic supra-molecular structure through inter-molecular hydrogen-bonding networks of the form O-H⋯O and N-H⋯O.

8-hydroxyquinoline-N-oxide copper(II)- and zinc(II)-phenanthroline and bipyridine coordination compounds: Design, synthesis, structures, and antitumor evaluation.

Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO3)]·CH3OH (NQ3), [Cu(ONQ)(QD2)(NO3)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), [Cu(ONQ)(QD3)](NO3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC50 value of 0.17 ± 0.05 µM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.

From 0D-complex to 3D-MOF: changing the antimicrobial activity of zinc(II) via reaction with aminocinnamic acids.

Combining zinc nitrate with 3- and/or 4- aminocinnamic acid (3-ACA and 4-ACA, respectively) leads to the formation of the 0D complex [Zn(4-AC)2(H2O)2], the 1D coordination polymer [Zn(3-AC)(4-AC)], and the 2D and 3D MOFs [Zn(3-AC)2]∙2H2O and [Zn(4-AC)2]∙H2O, respectively. These compounds result from the deprotonation of the acid molecules, with the resulting 3- and 4-aminocinnamate anions serving as bidentate terminal or bridging ligands. All solids were fully characterized via single crystal and powder X-ray diffraction and thermal techniques. Given the mild antimicrobial properties of cinnamic acid derivatives and the antibacterial nature of the metal cation, these compounds were assessed and demonstrated very good planktonic cell killing as well as inhibition of biofilm growth against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.

Different Zn(II) cation coordination geometries in di-µ-acetato-bis{2-chloro-6-[(pyridine-2-ylmethylimino)methyl]phenol}dizinc(II) chloroform monosolvate.

In the title compound, di-µ-acetato-κ(2)O:O;κ(2)O:O'-bis[(6-chloro-2-{(E)-[(pyridin-2-yl)methylimino]methyl}phenolato-κ(3)N,N',O)zinc(II)], [Zn2(C13H10ClN2O)2(C2H3O2)2]·CHCl3, the Zn(II) cation adopts a five-coordinate geometry and is coordinated by two N atoms and one O atom of a tridentate 6-chloro-2-{(E)-[(pyridin-2-yl)methylimino]methyl}phenolate ligand and two O atoms of two bridging acetate groups, but their coordination geometries differ. One Zn(II) cation adopts a distorted trigonal bipyramidal geometry and the other a square-pyramidal geometry. The two acetate ligands bridge two Zn(II) cations with mono- and bidentate coordination modes. The title compound exhibits a strong emission at 460 nm upon excitation at 325 nm with a quantum yield of 23.1%.

Divalent metal ion binding to Staphylococcus aureus FeoB transporter regions.

Transition metal ions such as iron, copper, zinc, manganese or, nickel are essential in many biological processes. Bacteria have developed a number of mechanisms for their acquisition and transport, in which numerous of proteins and smaller molecules are involved. One of the representatives of these proteins is FeoB, which belongs to the Feo (ferrous ion transporter) family. Although ferrous iron transport system is widespread among microorganisms, it is still poorly described in Gram-positive pathogens, such as Staphylococcus aureus. In this work, combined potentiometric and spectroscopic studies (UV-Vis, CD and EPR) were carried out to determine Cu(II), Fe(II) and Zn(II) binding modes to FeoB fragments (Ac-IDYHKLMK-NH2, Ac-ETSHDKY-NH2, and Ac-SFLHMVGS-NH2). For the first time iron(II) complexes with peptides were characterized by potentiometry. All studied ligands are able to form a variety of thermodynamically stable complexes with transition metal ions. It was concluded that among the studied systems, the most effective metal ion binding is observed for the Ac-ETSHDKY-NH2 peptide. Moreover, comparing preferences of all ligands towards different metal ions, copper(II) complexes are the most stable ones at physiological pH.

SERS study of classical and newly ß-lactams-metal complexation based on in situ laser-induced coral reefs-like silver photomicroclusters: In vitro study of antibacterial activity.

The influence of metal complexation of two polar ß-lactam antibiotics was investigated using surface enhanced Raman spectroscopy (SERS) technique. SERS method was applied to track the structural changes and the degradation behaviour of the studied compounds upon Zinc (II) ions-complexation. In situ laser-induced coral reefs-like photomicroclusters have been utilized as a SERS platform. The produced coral reefs-like photomicroclusters were characterized using scanning electron microscopy (SEM) and transmission electron microscope (TEM). The antibacterial efficiency of the antibiotics was investigated and compared before and after metal complexation using two techniques; agar well diffusion and growth curve. To provide a detailed elucidation of the complexation reaction, mass fragmentation of metal- antibiotics complexes was investigated using liquid chromatography/mass spectrometric (LC/MS) technique. It was found that metal complexation of classical ß-lactam antibiotic (Ticarcillin) promoted the rate of its degradation, leading to a decrease of the antibacterial efficiency. On the other side, the antibacterial activity of the newly developed ß-lactam (Faropenem) has been greatly enhanced via metal-complexation reaction.

Novel glycosylation zinc(II)-cryptolepine complexes perturb mitophagy pathways and trigger cancer cell apoptosis and autophagy in SK-OV-3/DDP cells.

With the aim of shedding some light on the mechanism of action of zinc(II) complexes in antiproliferative processes and molecular signaling pathways, three novel glycosylated zinc(II)-cryptolepine complexes, i.e., [Zn(QA1)Cl2] (Zn(QA1)), [Zn(QA2)Cl2] (Zn(QA2)), and [Zn(QA3)Cl2] (Zn(QA3)), were prepared by conjugating a glucose moiety with cryptolepine, followed by complexation of the resulting glycosylated cryptolepine compounds N-((1-(2-morpholinoethyl)-1H-1,2,3-triazol-4-yl)methyl)-benzofuro[3,2-b]quinolin-11-amine (QA1), 2-(4-((benzofuro[3,2-b]quinolin-11-ylamino)methyl)-1H-1,2,3-triazol-1-yl)ethan-1-ol (QA2), and (2S,3S,4R,5R,6S)-2-(4-((benzofuro[3,2-b]quinolin-11-ylamino)-methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (QA3) with zinc(II), and their anticancer activity was evaluated. In MTT assays, Zn(QA1)-Zn(QA3) were more active against cisplatin-resistant ovarian SK-OV-3/DDP cancer cells (SK-OV-3cis) than ZnCl2 and the QA1-QA3 ligands, with IC50 values of 1.81 ± 0.50, 2.92 ± 0.32, and 1.01 ± 0.11 µM, respectively. Complexation of glycosylated cryptolepine QA3 with zinc(II) increased the antiproliferative activity of the ligand, suggesting that Zn(QA3) could act as a chaperone to deliver the active ligand intracellularly, in contrast with other cryptolepine metal complexes previously reported. In vivo and in vitro investigations suggested that Zn(QA3) exhibited enhanced anticancer activity with treatment effects comparable to those of the clinical drug cisplatin. Furthermore, Zn(QA1)-Zn(QA3) triggered SK-OV-3cis cell apoptosis through mitophagy pathways in the order Zn(QA1) > Zn(QA1) > Zn(QA2). These results demonstrate the potential of glycosylated zinc(II)-cryptolepine complexes for the development of chemotherapy drugs against cisplatin-resistant SK-OV-3cis cells.

Enhancing the biological properties of zinc complexes with bis(indolyl)methane groups: Synthesis, characterization, DNA interaction, and biocide activity.

The unprecedented mononucleated ligand (6,6-di(1H-indol-3-yl)-N,N-bis(pyridin-2-ylmethyl)hexan-1-amine (LC5) with an N3-donor set and its complexes [Zn(LC5)Cl2] • 2CH3OH (1) and [Zn(LC5)2](ClO4)2 (2), were successfully prepared. All compounds were fully characterized by a suite of physicochemical methods. Fluid 1H and 13C NMR spectroscopy, as well as DFT and TD-DFT calculations, were carried out to propose a viable structural arrangement for both complexes. The interaction between these compounds and DNA was monitored in the UV region where binding constants (Kb) were estimated (2 > 1 > LC5). These data were corroborated by DNA cleavage assays using groove binders, circular dichroism, and docking studies. Both complexes confirmed their biocide activity against selected microorganisms: Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, the filamentous fungi A. fumigatus and S. cerevisiae. Finally, the cytotoxic activities of 1 and 2 were tested against the erythroleukemia K562 cell line. For all biological studies, it was probed that the presence of the indole moieties and the zinc atoms in the chemical composition of the complexes studied could increase the magnitude of the activity following the order: 2 > 1 > LC5, where a linear relationship between the biological activity upon K562 cells (IC50) and DNA binding studies (Kb) was found.

Structure and in vitro and in silico biological activity of zinc(II) complexes with 3,5-dichloro-salicylaldehyde.

Five Zn(II) complexes with 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) in the absence or presence of N,N'-donor co-ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, or 2,2'-bipyridylamine) were synthesized and formulated as [Zn(3,5-diCl-salo)2(CH3OH)2] (1) and [Zn(3,5-diCl-salo)2(N,N'-donor)] (2-5), respectively, and characterized by diverse techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2 was investigated. In addition, their antimicrobial profile against two Gram-positive and two Gram-negative bacterial strains were investigated. The affinity of the complexes for calf-thymus DNA was examined by diverse techniques, and the DNA-binding constants of the complexes were determined. The cleavage ability of the complexes towards supercoiled circular pBR322 plasmid DNA was examined by agarose gel electrophoretic experiments. The binding of the complexes with bovine and human serum albumins was investigated in order to determine the corresponding binding constants and the binding subdomain. In order to explain the described in vitro activity of the compounds and possibly establish a rational approach in the mechanism of action, molecular docking studies were adopted on the crystal structure of E. coli and S. aureus DNA-gyrase, 5-lipoxygenase, and 5-lipoxygenase-activating protein.