RESUMEN

Narrow band red-emitting phosphors based on organo-Eu(III) complexes prove their energetic features with surprising performance in smart red/white LEDs, sensing, and biological fields. In this report, a series of unique Eu(III) complexes have been synthesized with coumarin integrated with a class of phenanthroline(Phen)/thiabendazole(TBZ) based ancillary ligands and dibenzoyl methane (DBM)/2-theonyl trifluoroacetone (TTA) as an anionic ligand. The computational study reveals that the TBZ/Phen-based neutral ligands are superior energy harvesters to those other reported analogue neutral ligands. All the Eu-complexes demonstrated outstanding red emission due to electric dipole (ED) transition (5D0 → 7F2) in solid, solution, and thin film with high quantum yield (QY). Theoretical analysis (TD-DFT) and experimental findings describe that the energy transfer (ET) from the ligand's triplet level to the Eu(III) ion is completely occurring. The Eu(III) complexes can potentially be used to fabricate intense hybrid white and red LEDs. All of the fabricated red LEDs revealed high luminous efficiency of radiation (LER) values. The fabricated blue LED based hybrid white LEDs displayed remarkable performance with a low correlated color temperature (5634 K), high color rendering index 88%, and CIE values (x = 0.33; y = 0.342) for 3Eu. By interaction with acid-base vapors, Eu-complexes displayed effectively alterable on-off-on luminescence. Further, cellular imaging shows that Eu-complexes can be a potential biomarker for cancer cell lines.

Asunto(s)

Cumarinas , Europio , Ensayo de Materiales , Fenantrolinas , Europio/química , Cumarinas/química , Humanos , Fenantrolinas/química , Estructura Molecular , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Tamaño de la Partícula , Imagen Óptica , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Mediciones Luminiscentes , Sustancias Luminiscentes/química , Sustancias Luminiscentes/síntesis química

RESUMEN

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a-f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a-f) were characterized using 1H, 13C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts' structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC50 value of 12.8 ± 1.2 µM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using 1H NMR spectroscopy and its binding modes with DNA were explored via UV-Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.

Asunto(s)

Antineoplásicos , Apoptosis , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Imidazoles , Fenantrolinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Imidazoles/farmacología , Imidazoles/química , Imidazoles/síntesis química , Simulación del Acoplamiento Molecular , Estructura Molecular , Fenantrolinas/química , Fenantrolinas/farmacología , Fenantrolinas/síntesis química , Sales (Química)/química , Sales (Química)/farmacología , Sales (Química)/síntesis química , Relación Estructura-Actividad , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/farmacología

RESUMEN

In the present study, the drug delivery by albumin protein and antiproliferetaive activity of new transition metal complex i.e., [Pd (phen)(SSA)] (where phen and SSA represent 1, 10 phenanthroline and sulfosalicylic acid, respectively) was investigated. DFT (density functional theory) calculations were conducted at B3LYP level with 6-311G(d,p)/aug-ccpVTZ-PP basis set for the purpose of geometry optimization, frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP), and natural bond orbital (NBO) analysis. Experimental tests were conducted to preliminarily assess the lipophilicity and antitumor activity of the metal complex, resulting in promising findings. In-silico prediction was accomplished to assess its toxicity and bioavailability. To evaluate the binding of the newly formed complex with DNA (which results in halting the cell cycle) or serum albumin protein (drug transporter to the tissues), in-silico molecular modeling was employed. Experimental results (spectroscopic and non-spectroscopic) showed that the new compound interacts with each biomolecule via hydrogen bond and van der Waals interactions. Molecular docking demonstrated the binding of this complex to the DNA groove and site I of BSA occurs mainly through hydrogen bonds. Molecular dynamics simulation confirmed the interactions between [Pd (phen)(SSA)] with DNA or BSA through stable hydrogen bonds.

Asunto(s)

Antineoplásicos , Simulación del Acoplamiento Molecular , Salicilatos , Antineoplásicos/química , Antineoplásicos/farmacología , Salicilatos/química , Salicilatos/farmacología , Humanos , Teoría Funcional de la Densidad , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Fenantrolinas/química , Fenantrolinas/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , ADN/química , ADN/metabolismo , Bencenosulfonatos

RESUMEN

We describe a non-chromatographic, ligand-free platform for the efficient purification of recombinant human lactoferrin (LF). The platform consists of a [metal:chelator] complex precipitate in the presence of osmotically active polyethylene glycol 6000 (PEG-6000). Purification is achieved in three stages. Following formation of the complex, LF is captured under neutral conditions by the aggregated complexes (Step I), a washing step follows (Step II) and then, (Step III) LF is extracted in pure form with 100 mM tribasic Na citrate buffer (pH 7). Of the four complexes investigated, [bathophenanthroline (batho)3:Fe2+] was determined to be the most efficient. LF is recovered with high yield (∼90%, by densitometry) and purity (≥97%, by SDS polyacrylamide gel electrophoresis (SDS-PAGE)) from an artificial contamination background comprising E. coli lysate proteins. Purified LF is demonstrated to be monomeric by dynamic light scattering (DLS); to preserve its native secondary structure by circular dichroism (CD) spectroscopy; and, as apo-LF, to efficiently inhibit bacterial growth. Process yield is not affected by a 45-fold increase in LF concentration from 0.2 to 9 mg/mL. We provide evidence that protein capture relies on [cation:π] interactions between the lysine and arginine residues of LF with the fully aromatic [(batho)3:Fe2+] complexes. The use of [metal:chelator] complex aggregates is demonstrated to provide an economical and efficient avenue for LF purification.

Asunto(s)

Lactoferrina , Humanos , Lactoferrina/aislamiento & purificación , Lactoferrina/química , Fenantrolinas/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/química , Electroforesis en Gel de Poliacrilamida , Dicroismo Circular , Polietilenglicoles/química , Hierro/química

RESUMEN

Cancer is a serious global health problem, causing the loss of millions of lives each year. Plumbagin, a compound derived from the medicinal plant Plumbago zeylanica, has shown promise in stopping the growth of tumor cells both in laboratory settings and in living organisms. Many plant-based compounds exert their effects through copper's ability to produce reactive oxygen species (ROS). This study aimed to understand how plumbagin, dependent on copper, induces cell death (apoptosis) in human cancer cells through various experiments. The results demonstrate that plumbagin hinders the growth of pancreatic cancer cells PNAC-1 and MIA PaCa-2 by utilizing the copper naturally present in the cells. Unlike metal chelators that remove iron and zinc (desferrioxamine mesylate and histidine), a specific copper chelator called neocuproine lessens the cell death caused by plumbagin. When ROS scavengers are used, plumbagin-induced apoptosis is inhibited, indicating that ROS plays a role in initiating cell death. The study also proves that plumbagin prevents copper from leaving cancer cells by suppressing the expression of specific genes (CTR1 and ATP7A). It is confirmed that plumbagin targets the nuclear copper, leading to signals that promote oxidative stress and, ultimately, cell death. These findings provide valuable insights into the potential of plumbagin as a substance to combat cancer, highlighting the importance of understanding how copper behaves within cancer cells.

Asunto(s)

Apoptosis , Proliferación Celular , Cobre , Naftoquinonas , Especies Reactivas de Oxígeno , Humanos , Naftoquinonas/farmacología , Naftoquinonas/química , Cobre/química , Cobre/farmacología , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quelantes/farmacología , Quelantes/química , Fenantrolinas/química , Fenantrolinas/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos/farmacología , Antineoplásicos/química

RESUMEN

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH3)2Cl2], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu2(3-(4-hydroxyphenyl)propanoate)3(phenanthroline)2]Cl·H2O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Cobre , Fenantrolinas , Humanos , Cobre/química , Fenantrolinas/química , Fenantrolinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Ligandos , ADN/química , ADN/metabolismo , Células A549 , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Células MCF-7

RESUMEN

Organotin(IV) and iridium(III) complexes have shown good application potential in the field of anticancer; however, the aggregation-caused quenching (ACQ) effect induced by high concentration or dose has limited the research on their targeting and anticancer mechanism. Then, a series of aggregation-induced emission (AIE)-activated butyltin(IV)-iridium(III) imidazole-phenanthroline complexes were prepared in this study. Complexes exhibited significant fluorescence improvement in the aggregated state because of the restricted intramolecular rotation (RIR), accompanied by an absolute fluorescence quantum yield of up to 29.2% (IrSn9). Complexes demonstrated potential in vitro antiproliferative and antimigration activity against A549 cells, following a lysosomal-mitochondrial apoptotic pathway. Nude mouse models further confirmed that complexes had favorable in vivo antitumor and antimigration activity in comparison to cisplatin. Therefore, butyltin(IV)-iridium(III) imidazole-phenanthroline complexes possess the potential as potential substitutes for platinum-based drugs.

Asunto(s)

Antineoplásicos , Proliferación Celular , Complejos de Coordinación , Ensayos de Selección de Medicamentos Antitumorales , Imidazoles , Iridio , Fenantrolinas , Fenantrolinas/química , Fenantrolinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Humanos , Animales , Ratones , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Proliferación Celular/efectos de los fármacos , Imidazoles/química , Imidazoles/farmacología , Iridio/química , Iridio/farmacología , Ratones Desnudos , Apoptosis/efectos de los fármacos , Compuestos Orgánicos de Estaño/química , Compuestos Orgánicos de Estaño/farmacología , Compuestos Orgánicos de Estaño/síntesis química , Estructura Molecular , Células A549

RESUMEN

Simple and sensitive determination of total antioxidant capacity (TAC) in food samples is highly desirable. In this work, an electrochemical platform was established based on a silica nanochannel film (SNF)-modified electrode, facilitating fast and highly sensitive analysis of TAC in colored food samples. SNF was grown on low-cost and readily available tin indium oxide (ITO) electrode. Fe3+-phenanthroline complex-Fe(III)(phen)3 was applied as the probe, and underwent chemical reduction to form Fe2+-phenanthroline complex-Fe(II)(phen)3 in the presence of antioxidants. Utilizing an oxidative voltage of +1 V, chronoamperometry was employed to measure the current generated by the electrochemical oxidation of Fe(II)(phen)3, allowing for the assessment of antioxidants. As the negatively charged SNF displayed remarkable enrichment towards positively charged Fe(II)(phen)3, the sensitivity of detection can be significantly improved. When Trolox was employed as the standard antioxidant, the electrochemical sensor demonstrated a linear detection range from 0.01 µM to 1 µM and from 1 µM to 1000 µM, with a limit of detection (LOD) of 3.9 nM. The detection performance is better that that of the conventional colorimetric method with a linear de range from 1 µM to 40 µM. Owing to the anti-interfering ability of nanochannels, direct determination of TAC in colored samples including coffee, tea, and edible oils was realized.

Asunto(s)

Antioxidantes , Técnicas Electroquímicas , Electrodos , Análisis de los Alimentos , Oxidación-Reducción , Antioxidantes/análisis , Antioxidantes/química , Técnicas Electroquímicas/métodos , Análisis de los Alimentos/métodos , Límite de Detección , Fenantrolinas/química , Dióxido de Silicio/química

RESUMEN

Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or dipyrido[3,2-a:2'3'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 µM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 µM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

Asunto(s)

Antineoplásicos , Complejos de Coordinación , ADN , Renio , Renio/química , Humanos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , ADN/química , ADN/metabolismo , Fenantrolinas/química , Fenantrolinas/farmacología , Quinoxalinas/química , Quinoxalinas/farmacología , Fenazinas/química , Fenazinas/farmacología , Línea Celular Tumoral , Células HeLa

RESUMEN

Considerable attention has been devoted to the exploration of organometallic iridium(III) (IrIII) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich IrIII imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic non­platinum anticancer drugs.

Asunto(s)

Antineoplásicos , Apoptosis , Complejos de Coordinación , Imidazoles , Iridio , Fenantrolinas , Humanos , Iridio/química , Iridio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Fenantrolinas/química , Fenantrolinas/farmacología , Imidazoles/química , Imidazoles/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Células A549 , Especies Reactivas de Oxígeno/metabolismo , Fenantrenos/química , Fenantrenos/farmacología , Proliferación Celular/efectos de los fármacos , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos

RESUMEN

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [Ru2L1, Ru2L2, Ir2L1, Ir2L2, Re2L1, and Re2L2] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru2L1 and Ir2L2 are two proficient complexes among all, but Ru2L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕf) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru2L1-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir2L2-treated cells, which correlated with autophagy reticence.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Mitocondrias , Células Madre Neoplásicas , Fenantrolinas , Rutenio , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Fenantrolinas/química , Fenantrolinas/farmacología , Rutenio/química , Rutenio/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Iridio/química , Iridio/farmacología , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad

RESUMEN

Platinum-based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water-soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1-C2H4OEt)(phen)] (1, phen=1,10-phenanthroline) precursor, specifically [Pt(NH3)(η1-C2H4OEt)(phen)]Cl (2), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl (3), and [Pt(1-hexyl-1H-benzo[d]imidazole)(η1-C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki-1), and normal human renal cells (HK-2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki-1) among the tested complexes, compared to healthy cells (HK-2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum-based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.

Asunto(s)

Antineoplásicos , Imidazoles , Fenantrolinas , Solubilidad , Agua , Humanos , Fenantrolinas/química , Fenantrolinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Imidazoles/química , Imidazoles/farmacología , Ligandos , Agua/química , Línea Celular Tumoral , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Cisplatino/farmacología , Platino (Metal)/química , Cationes/química , Compuestos Organoplatinos/química , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/síntesis química , Células HeLa , Ensayos de Selección de Medicamentos Antitumorales

RESUMEN

BACKGROUND: Aberrant expression of histone deacetylases (HDACs) and ribonucleotide reductase (RR) enzymes are commonly observed in various cancers. Researchers are focusing on these enzymes in cancer studies with the aim of developing effective chemotherapeutic drugs for cancer treatment. Targeting both HDAC and RR simultaneously with a dual HDAC/RR inhibitor has exhibited enhanced effectiveness compared to monotherapy in cancer treatment, making it a promising strategy. OBJECTIVES: The objective of the study is to synthesize and assess the anti-cancer properties of a 1,10-phenanthroline-based hydroxamate derivative, characterizing it as a novel dual HDAC/RR inhibitor. METHODS: The N1-hydroxy-N8-(1,10-phenanthrolin-5-yl)octanediamide (PA), a 1,10-phenanthroline-based hydroxamate derivative, was synthesized and structurally characterized. The compound was subjected to in vitro assessments of its anti-cancer, HDAC, and RR inhibitory activities. In silico docking and molecular dynamics simulations were further studied to explore its interactions with HDACs and RRM2. RESULTS: The structurally confirmed PA exhibited antiproliferative activity in SiHa cells with an IC50 of 16.43 µM. It displayed potent inhibitory activity against HDAC and RR with IC50 values of 10.80 µM and 9.34 µM, respectively. Co-inhibition of HDAC and RR resulted in apoptosis-induced cell death in SiHa cells, mediated by the accumulation of reactive oxygen species (ROS). In silico docking studies demonstrated that PA can effectively bind to the active sites of HDAC isoforms and RRM2. Furthermore, PA demonstrated a more favorable interaction with HDAC7, displaying a docking score of -9.633 kcal/mol, as compared to the standard HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), which exhibited a docking score of -8.244 kcal/mol against HDAC7. CONCLUSION: The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.

Asunto(s)

Antineoplásicos , Proliferación Celular , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos , Simulación del Acoplamiento Molecular , Fenantrolinas , Humanos , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Fenantrolinas/química , Fenantrolinas/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Simulación de Dinámica Molecular , Histona Desacetilasas/metabolismo , Histona Desacetilasas/química , Ribonucleótido Reductasas/antagonistas & inhibidores , Ribonucleótido Reductasas/química , Apoptosis/efectos de los fármacos

RESUMEN

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.

Asunto(s)

Inhibidores de la Angiogénesis , Antineoplásicos , Apoptosis , Complejos de Coordinación , Fenantrolinas , Neoplasias de la Mama Triple Negativas , Apoptosis/efectos de los fármacos , Humanos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Animales , Fenantrolinas/farmacología , Fenantrolinas/química , Fenantrolinas/síntesis química , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/síntesis química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Sinergismo Farmacológico , Relación Estructura-Actividad , Ratones Endogámicos BALB C , Ensayos de Selección de Medicamentos Antitumorales

RESUMEN

Development of metal-free nanozymes has raised concern for their extensive applications in photocatalysis and sensing fields. As novel metal-free nanomaterials, covalent organic frameworks (COFs) have engendered intense interest in the construction of nanozymes due to their structural controllability and molecular functionality. The formation of the molecular arrangement by embedding orderly donor-acceptors (D-A) linked in the framework topology to modulate material properties for highly efficient enzyme mimicking activity is of importance but challenging. Here, a strong D-A type of COF was designed and synthesized by integrating electron donor units (pyrene) and electron acceptor units (phenanthroline), named Py-PD COF. Using experiments and theoretical calculations, the introduction of a phenanthroline ring endowed the Py-PD COF with a narrowed band gap, and efficient charge transfer and separation. Further, the Py-PD COF exhibited a superior light-responsive oxidase-mimicking characteristic under visible light irradiation, which could catalyze the oxidation of 3,3',5,5-tetramethylbenzidine (TMB) and give the corresponding evolution of color. The nanoenzymatic activity of the Py-PD COF was light-regulated, which offers a fascinating advantage because of its high efficiency and spatial controllability. Based on previously mentioned characteristics, an "on-off" sensing platform for the colorimetric analysis of isoniazid (INH) could be constructed with a good linear relationship (2-100 µM) and a low limit of detection (1.26 µM). This research shows that not only is Py-PD COF an environmentally friendly compound for the colorimetric detection of INH, but it is also capable of providing the interesting D-A type COF-based material for designing an excellent nanozyme.

Asunto(s)

Colorimetría , Isoniazida , Estructuras Metalorgánicas , Fenantrolinas , Colorimetría/métodos , Estructuras Metalorgánicas/química , Fenantrolinas/química , Isoniazida/química , Isoniazida/análisis , Procesos Fotoquímicos , Luz , Nanoestructuras/química , Tamaño de la Partícula , Catálisis , Estructura Molecular

RESUMEN

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

Asunto(s)

Antineoplásicos , Fenantrolinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ligandos , Células HeLa , Fenantrolinas/química , Fenantrolinas/farmacología , Renio/química , Renio/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/efectos de la radiación , Apoptosis/efectos de los fármacos , Luz , Especies Reactivas de Oxígeno/metabolismo , Terapia por Ultrasonido , Fotoquimioterapia , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico

RESUMEN

Copper can be opportunely complexed to modulate oncogenic pathways, being a promising strategy for cancer treatment. Herein, three new copper(II) complexes containing long-chain aliphatic hydrazides and 1,10-phenanthroline (1,10-phen), namely, [Cu(octh)(1,10-phen)(H2O)](NO3)21, [Cu(dech)(1,10-phen)(H2O)](NO3)22 and [Cu(dodh)(1,10-phen)(H2O)](NO3)2.H2O 3 (where octh = octanoic hydrazide, dech = decanoic hydrazide, dodh = dodecanoic hydrazide) were successfully prepared and characterized by several physical-chemical methods. Furthermore, X-ray structural analysis of complex 2 indicated that the geometry around the copper(II) ion is distorted square-pyramidal, in which hydrazide and 1,10-phenanthroline act as bidentate ligands. A water molecule in the apical position completes the coordination sphere of the metal ion. All new copper(II) complexes were cytotoxic to breast cancer cell lines (MCF7, MDA-MB-453, MDA-MB-231, and MDA-MB-157) and selective when compared to the non tumor lineage MCF-10A. In particular, complex 2 showed half-maximal inhibitory concentration (IC50) values ranging between 2.7 and 13.4 µM in MDA-MB231 cells after 24 and 48 h of treatment, respectively. Furthermore, this complex proved to be more selective for tumor cell lines when compared to doxorubicin and docetaxel. Complex 2 inhibited the clonogenicity of MDA-MB231 cells, increasing adenosine diphosphate (ADP) hydrolysis and upregulating ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1) transcriptional levels. In this sense, we suggest that the inhibitory effect on cell proliferation may be related to the modulation of adenosine monophosphate (AMP) levels. Thus, a novel copper(II) complex with increased cytotoxic effects and selectivity against breast cancer cells was obtained, contributing to medicinal chemistry efforts toward the development of new chemotherapeutic agents.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Neoplasias de la Mama Triple Negativas , Humanos , Cobre/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Hidrazinas , Hidrólisis , Antineoplásicos/farmacología , Antineoplásicos/química , Fenantrolinas/farmacología , Fenantrolinas/química , Adenosina Difosfato , Cristalografía por Rayos X

RESUMEN

With the great progress on determining protein structures over the last decade comes a renewed appreciation that structures must be combined with dynamics and energetics to understand function. Fluorescence spectroscopy, specifically Förster resonance energy transfer (FRET), provides a great window into dynamics and energetics due to its application at physiological temperatures and ability to measure dynamics on the ångström scale. We have recently advanced transition metal FRET (tmFRET) to study allosteric regulation of maltose binding protein and have reported measurements of maltose-dependent distance changes with an accuracy of ∼1.5 Å. When paired with the noncanonical amino acid Acd as a donor, our previous tmFRET acceptors were useful over a working distance of 10 to 20 Å. Here, we use cysteine-reactive bipyridyl and phenanthroline compounds as chelators for Fe2+ and Ru2+ to produce novel tmFRET acceptors to expand the working distance to as long as 50 Å, while preserving our ability to resolve even small maltose-dependent changes in distance. We compare our measured FRET efficiencies to predictions based on models using rotameric ensembles of the donors and acceptors to demonstrate that steady-state measurements of tmFRET with our new probes have unprecedented ability to measure conformational rearrangements under physiological conditions.

Asunto(s)

Transferencia Resonante de Energía de Fluorescencia , Fenantrolinas , Fenantrolinas/química , Ligandos , 2,2'-Dipiridil/química , 2,2'-Dipiridil/análogos & derivados , Maltosa/química , Maltosa/metabolismo , Maltosa/análogos & derivados , Proteínas de Unión a Maltosa/química , Proteínas de Unión a Maltosa/metabolismo

RESUMEN

Three new molecular complexes (phen)3(2-amino-Bz)2(H+)(BF4-)·3H2O 5, (phen)3(2-amino-5(6)-methyl-Bz)2(H+)(BF4-)·H2O 6, and (phen)(1-methyl-2-amino-Bz)(H+)(BF4-) 7, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of 7 is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules 5 and 6 were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF4- ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules 5-7 are promising DNA-binding anticancer agents warranting further in-depth exploration.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Humanos , Fenantrolinas/química , Bencimidazoles/farmacología , Cristalografía por Rayos X , Antineoplásicos/química , ADN/química , Complejos de Coordinación/química , Cobre/química , Estructura Molecular

RESUMEN

The experimental study of the DNA interaction with three cadmium coordination compounds [Cd(phen)3](CH3CO2)2, [Cd(phen)2(H2O)2](CH3CO2)2, and [Cd2(phen)4(H2O)2](CH3CO2)4 was carried out using spectrophotometry, viscosity, and dynamic light scattering methods. The role of the solution ionic strength (concentration of NaCl) was analyzed. All compounds can penetrate (fully or partly) to the major or minor DNA grooves. It was shown that, in addition to the important role of electrostatic interactions in the formation of the complex, intercalation of the 1,10-phenanthroline ligand occurs for compounds [Cd(phen)2(H2O)2](CH3CO2)2 and [Cd2(phen)4(H2O)2](CH3CO2)4. Compound [Cd(phen)3](CH3CO2)2 binds to DNA externally. The coordination bond between cadmium and DNA was formed in DNA complexes with [Cd2(phen)4(H2O)2](CH3CO2)4. Preliminary computer modeling of the DNA interaction with the compounds used was performed.

Asunto(s)

Complejos de Coordinación , Compuestos Organometálicos , Cadmio , Dióxido de Carbono , ADN/química , Espectrofotometría , Fenantrolinas/química , Ligandos , Complejos de Coordinación/química , Compuestos Organometálicos/química