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1.
Sci Rep ; 14(1): 10076, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698064

RESUMO

While COVID-19 becomes periodical, old individuals remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, researchers rarely provide a comprehensive analysis to reveal the relationships and interactive effects of the risk factors of COVID-19 mortality, especially in the elderly. Through retrospectively including 1917 COVID-19 patients (102 were dead) admitted to Xiangya Hospital from December 2022 to March 2023, we used the association rule mining method to identify the risk factors leading causes of death among the elderly. Firstly, we used the Affinity Propagation clustering to extract key features from the dataset. Then, we applied the Apriori Algorithm to obtain 6 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. Patients with "C-reactive protein > 8 mg/L", "neutrophils percentage > 75.0 %", "lymphocytes percentage < 20%", and "albumin < 40 g/L" have a 2 × mortality rate than the basic one. When the characteristics of "D-dimer > 0.5 mg/L" and "WBC > 9.5 × 10 9 /L" are continuously included in this foundation, the mortality rate can be increased to 3 × or 4 × . In addition, we also found that liver and kidney diseases significantly affect patient mortality, and the mortality rate can be as high as 100%. These findings can support auxiliary diagnosis and treatment to facilitate early intervention in patients, thereby reducing patient mortality.


Assuntos
COVID-19 , Mineração de Dados , Humanos , COVID-19/mortalidade , Idoso , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Idoso de 80 Anos ou mais , Algoritmos
2.
Eur J Med Chem ; 272: 116497, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38759453

RESUMO

A series of combretastatin A-4 (CA-4) derivatives were designed and synthesized, which contain stilbene core structure with different linker, predominantly piperazine derivatives. These compounds were evaluated for their cytotoxic activities against four cancer cell lines, HCT116, A549, AGS, and SK-MES-1. Among them, compound 13 displayed the best effectiveness with IC50 values of 0.227 µM and 0.253 µM against HCT116 and A549 cells, respectively, showing low toxicity to normal cells. Mechanistic studies showed that 13 inhibited HCT116 proliferation via arresting cell cycle at the G2/M phase through disrupting the microtubule network and inducing autophagy in HCT116 cells by regulating the expression levels of autophagy-related proteins. In addition, 13 displayed antiproliferative activities against A549 cells through blocking the cell cycle and inducing A549 cells apoptosis. Because of the poor water solubility of 13, four carbohydrate conjugates were synthesized which exhibited better water solubility. Further investigations revealed that 13 showed positive effects in vivo anticancer study with HCT116 xenograft models. These data suggest that 13 could be served as a promising lead compound for further development of anti-colon carcinoma agent.

3.
Langmuir ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739267

RESUMO

Surfactant-free microemulsions (SFMEs) exhibited remarkable advantages and potential, attributed to their similarity to traditional surfactant-based microemulsions and the absence of surfactants. Herein, a novel SFME was developed utilizing cosmetically approved materials, such as short-chain alcohol as an amphi-solvent, triethyl citrate (TEC) as the nonpolar phase, and water as the polar phase. 1,2-Pentanediol (PtDO)/TEC/water combination can form the largest monophasic zone, accounting for ∼74% of the total phase diagram area, due to an optimal hydrophilic (water)-lipophilic (TEC) balance. Comparable to surfactant-based microemulsion, PtDO/TEC/water SFME can also be categorized into three types: water-in-oil, discontinuous, and oil-in-water. As TEC or water is increased, or PtDO is decreased, the nanoaggregates in PtDO/TEC/water SFME grow from <5 nm to tens of nanometers. The addition of α-arbutin (ABN) does not disrupt PtDO/TEC/water SFME, but rather enhances its formation, resulting in a larger monophasic area and consistent size (2.8-3.8 nm) through participating in interface assembly. Furthermore, ABN-loaded PtDO/TEC/water SFME exhibits remarkable resistance to dilution, exceptional stability, and minimal irritation. Notably, PtDO/TEC/water SFME significantly boosts ABN's solubility in water by 2 times, its percutaneous penetration rate by 3-4 times, and enables a slow-release DPPH• radical scavenging effect. This SFME serves as a safe and cosmetically suitable nanoplatform for the delivery of bioactive substances.

4.
Int J Biol Macromol ; 268(Pt 2): 131944, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692531

RESUMO

Efficient removal and recycling of phosphorus from complex water matrices using environmentally friendly and sustainable materials is essential yet challenging. To this end, a novel bio-based adsorbent (DX-FcA-CS) was developed by coupling oxidized dextran-crosslinked chitosan with ferrocene carboxylic acid (FcA). Detailed characterization revealed that the incorporation of FcA reduced the total pore area of DX-FcA-CS to 7.21 m2·g-1, one-third of ferrocene-free DX-CS (21.71 m2·g-1), while enhancing thermal stability and PO43- adsorption performance. Adsorption kinetics and isotherm studies demonstrated that the interaction between DX-FcA-CS and PO43- followed a pseudo-second-order kinetic model and Langmuir model, indicating chemical and monolayered adsorption mechanisms, respectively. Moreover, DX-FcA-CS exhibited excellent anti-interference properties against concentrated co-existing inorganic ions and humic acid, along with high recyclability. The maximum adsorption capacity reached 1285.35 mg·g-1 (∼428.45 mg P g-1), three times that of DX-CS and surpassing many other adsorbents. PO43--loaded DX-FcA-CS could be further carbonized into electrode material due to its rich content of phosphorus and nitrogen, transforming waste into a valuable resource. These outstanding characteristics position DX-FcA-CS as a promising alternative for phosphate capture and recycling. Overall, this study presents a viable approach to designing environmentally friendly, recyclable, and cost-effective biomaterial for wastewater phosphate removal and value-added applications.


Assuntos
Quitosana , Fosfatos , Quitosana/química , Adsorção , Porosidade , Fosfatos/química , Cinética , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Águas Residuárias/química , Fósforo/química
5.
Eur J Med Chem ; 271: 116398, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614061

RESUMO

In contemporary studies, the predominant utilization of C60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality within the biomedical domain, owing to its notable levels of safety and efficacy. The essential components of photodynamic therapy encompass light of the suitable wavelength, oxygen, and a photosensitizer, wherein the reactive oxygen species generated by the photosensitizer play a pivotal role in the therapeutic mechanism. The remarkable ability of fullerenes to generate singlet oxygen has garnered significant attention from scholars worldwide. Nevertheless, the limited permeability of fullerenes across cell membranes owing to their low water solubility necessitates their modification to enhance their efficacy and utilization. This paper reviews the applications of fullerene derivatives as photosensitizers in antitumor and antibacterial fields for the recent years.


Assuntos
Antibacterianos , Antineoplásicos , Fulerenos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fulerenos/química , Fulerenos/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Estrutura Molecular , Neoplasias/tratamento farmacológico
6.
Eur J Med Chem ; 269: 116294, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38508119

RESUMO

Lamellarins are polyaromatic alkaloids isolated from marine organisms, including mollusks, tunicates, and sponges. Currently, over 60 structurally distinct natural lamellarins have been reported, and most of them exhibit promising biological activities, such as topoisomerase inhibition, mitochondrial function inhibition, multidrug resistance reversing, and anti-HIV activity. There has also been a significant progress on the synthetic study of lamellarins which has been regularly updated by numerous medicinal chemists as well. This review provides a detailed summary of the synthesis, pharmacology, and structural modification of lamellarins over the past decades.


Assuntos
Alcaloides , Produtos Biológicos , Urocordados , Animais , Relação Estrutura-Atividade , Resistência a Múltiplos Medicamentos , Mitocôndrias , Urocordados/química , Alcaloides/química
7.
Biomater Sci ; 12(9): 2302-2311, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38497169

RESUMO

Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.


Assuntos
Colagenases , Doxorrubicina , Colagenases/metabolismo , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Camundongos , Polímeros/química , Polímeros/metabolismo , Humanos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Ácido Poliglutâmico/química , Portadores de Fármacos/química
8.
Biochem Pharmacol ; 222: 116077, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38395264

RESUMO

Compound G-4 is a derivate of cyclin-dependent kinase inhibitor Rocovitine and showed strong sensitivity to triple negative breast cancer (TNBC) cells. In this study, the antitumor activity, mechanism and possible targets of G-4 in TNBC were investigated. Flow cytometry and immunoblotting showed that G-4 not only arrested the S phase of the cell cycle, but also induced apoptosis in TNBC cells via the mitochondrial pathway through inhibiting epidermal growth factor receptor (EGFR), AKT and MAPK pathways. In addition, G-4 induced the iron-mutagenesis process in TNBC cells and down-regulated differentially expressed gene lipid carrier protein 2 (LCN2) by RNA-seq. Moreover, G-4 elevated levels of cytosolic reactive oxygen species (ROS), lipid ROS, Fe and malondialdehyde (MDA), but decreased levels of superoxide dismutase (SOD) and glutathione (GSH), consistent with the effects of iron-mutagenic agonists Erastin and RSL3, which were inhibited by the iron inhibitor ferrostatin-1 (Fer-1). Furthermore, a LCN2 knockdown cell model was established by siRNA transfection, the IC50 of G-4 was increased nearly 100-fold, accompanied by a trend of no ferroptosis characteristic index. The results indicated that G-4 suppressed the malignant phenotype of TNBC, induced apoptosis by inhibiting EGFR pathway and promoted LCN2-dependent ferroptosis.


Assuntos
Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas de Transporte/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Apoptose , Receptores ErbB/metabolismo , Ferro/metabolismo , Lipídeos/farmacologia , Lipocalina-2
9.
Int J Biol Macromol ; 261(Pt 1): 129699, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281517

RESUMO

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m2·g-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H2O2/K2S2O8 through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H2O2/K2S2O8, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H2O2/K2S2O8, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive 1O2 and ·OH. The significant contribution from 1O2 endowed CS-FC/H2O2/K2S2O8 with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.


Assuntos
Compostos Azo , Quitosana , Poluentes Ambientais , Compostos Ferrosos , Poluentes Químicos da Água , Metalocenos , Microesferas , Peróxido de Hidrogênio , Adsorção , Concentração de Íons de Hidrogênio , Cinética
10.
Biol Direct ; 19(1): 11, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38268026

RESUMO

BACKGROUND: To create a dual-acting vaccine that can fight against tuberculosis, we combined antigenic arabino-mannan analogues with the Ag85B protein. To start the process, we studied the impact of modifying different parts of the Ag85B protein on its ability to be recognized by antibodies. RESULTS: Through our research, we discovered that three modified versions of the protein, rAg85B-K30R, rAg85B-K282R, and rAg85B-K30R/K282R, retained their antibody reactivity in healthy individuals and those with tuberculosis. To further test the specificity of the sugar AraMan for AraMan antibodies, we used Human Serum Albumin glycosylated with AraMan-IME and Ara3Man-IME. Our findings showed that this specific sugar was fully and specifically modified. Bio-panning experiments revealed that patients with active tuberculosis exhibited a higher antibody response to Ara3Man, a sugar found in lipoarabinomannan (LAM), which is a major component of the mycobacterial cell wall. Bio-panning with anti-LAM plates could eliminate this increased response, suggesting that the enhanced Ara3Man response was primarily driven by antibodies targeting LAM. These findings highlight the importance of Ara3Man as an immunodominant epitope in LAM and support its role in eliciting protective immunity against tuberculosis. Further studies evaluated the effects of glycosylation on the antibody affinity of recombinant Ag85B and its variants. The results indicated that rAg85B-K30R/K282R, when conjugated with Ara3Man-IME, demonstrated enhanced antibody recognition compared to unconjugated or non-glycosylated versions. CONCLUSIONS: Coupling Ara3Man to rAg85B-K30R/K282R could lead to the development of effective dual-acting vaccines against tuberculosis, stimulating protective antibodies against both AraMan and Ag85B, two key tuberculosis antigens.


Assuntos
Tuberculose , Vacinas , Humanos , Glicosilação , Tuberculose/prevenção & controle , Açúcares
11.
Bioorg Chem ; 143: 107031, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086242

RESUMO

Hypobromous acid (HOBr), one of the significant reactive oxygen species (ROS) that acts as an important role in human immune system, however the increasing level of HOBr in human body can cause the disorder of eosinophils (EPO), leading to oxidative stress in organelles, and further causing a series of diseases. In this study, a ratiometric fluorescent probe DMBP based on Nile red skeleton was developed to detect HOBr specifically by the electrophilic substitution with HOBr. DMBP emits near-infrared (NIR) fluorescence at 653 nm, after reacting with HOBr, the emission wavelength of DMBP shifted blue and a new peak appeared at 520 nm, realizing a ratiometric examination of HOBr with a limit of detection of 89.00 nM. Based on its sensitive and specific response to HOBr, DMBP was applied in the visual imaging of HOBr in HepG2 cells and zebrafish. Foremost, probe DMBP has excellent lysosome targeting ability and NIR emission reduced the background interference of biological tissues, providing a potential analytical tool to further investigate the role of HOBr in lysosome.


Assuntos
Bromatos , Corantes Fluorescentes , Oxazinas , Árvores , Animais , Humanos , Peixe-Zebra , Lisossomos , Esqueleto
12.
Environ Res ; 242: 117766, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029811

RESUMO

Theoretically, agricultural insurance influences farmers' use of pesticides by changing the expected income of agricultural production. Full-cost insurance, with high guarantee and high compensation characteristics, may significantly affect farmers' pesticide use. First, this paper constructs a production function to characterize and compare the marginal incomes of insured and uninsured farmers under risk uncertainty and analyses how insured farmers can increase marginal income by increasing or reducing factor inputs. Considering scale differentiation, it discusses pesticide use strategies different types of farmers may adopt to maximize household utility. Second, using survey data of the pilot counties of full-cost insurance for wheat in Henan Province, China, the simultaneous equation model is used for empirical testing. The results reveal the following: (i) Farmers' insurance participation and pesticide application behaviour are not mutually independent. (ii) For the whole sample, full-cost insurance for wheat has a significant pesticide reduction effect. (iii) However, considering scale differentiation, pesticide application decreases significantly among insured ordinary farmers but does not change significantly among insured large-scale farmers. Third, policy measures are proposed to activate the green development function of agricultural insurance.


Assuntos
Praguicidas , Humanos , Fazendeiros , Triticum , Conhecimentos, Atitudes e Prática em Saúde , Agricultura , China
13.
Langmuir ; 40(1): 938-949, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38134444

RESUMO

The superamphiphiles exhibit broad prospects for fabricating stimuli-responsive emulsions. Because the superamphiphiles are assembled via noncovalent interactions, they have the advantage of fast response and high efficiency. Recently, a series of switchable emulsions using CO2-responsive superamphiphiles have been developed, which extends the applications of CO2-responsive materials in widespread field. However, there is still a lack of fundamental understanding on the switching mechanism related to the assembled structure of superamphiphiles at the oil-water interface. We employed molecular dynamics (MD) simulations to investigate the reversible emulsification/demulsification process of a responsive emulsion system stabilized by a recently developed responsive superamphiphile (BTOA), which consists of oleic acid (OA) and cationic amine (named 1,3-bis(aminopropyl)tetramethyldisiloxane, BT). The simulation results present the morphologies in both the emulsion and demulsification states. It is found that the ionized OA- and the protonated BT+ together form an adsorption layer at the oil-water interface. The hydrophobic parts of BT+ are inserted into the adsorption layer, and the two amine groups contact the water phase. This adsorption layer reduces the interfacial tension and stabilizes the emulsion. After the bubbling of CO2, the surfactants were fully protonated to OA and BT2+. Because of the changes in the molecular polarity, OA and BT2+ entered the oil and water phases, respectively, resulting in demulsification. The structural and dynamical properties were analyzed to reveal the different intermolecular interactions that were responsible for the reversible reversibility of the emulsion. The observations are considered to be complementary to experimental studies and are expected to provide deeper insights into studies on developing responsive materials via supramolecular assemblies.

14.
Curr Med Chem ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38013439

RESUMO

α-Glucosidase inhibitors (AGIs) showcase versatile biochemical activities with respect to antidiabetic, anticancerous, antiobese and antiviral effects. They have drawn a great deal of attention from the scientific community. While α-glucosidase inhibitors are mostly discovered from plants and microorganisms, the recent advance in natural αglucosidase inhibitors over the past five years has been reviewed in this article, and 139 distinct α-glucosidase inhibitors from the plants and microorganisms were classified into ten groups based on their chemical structures, including flavonoids (34), xanthones (6), alkaloids (8), benzopyrones / benzofuranones (8), terpenes (23), saponins (8), phenols / alcohols (25), esters (18), chalcone (5) and other compounds (4). In this review, we mainly focused on the novel chemical structures and the various biological activities of theses natural AGIs. Some of the selected natural compounds exhibit powerful α-glucosidase inhibitory activity and anti-tumor activity, may hold promise to become the candidate drugs for treating type II diabetes and cancer in future.

15.
Eur J Med Chem ; 261: 115797, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37708799

RESUMO

Triple negative breast cancer (TNBC) is considered to be the most difficult subtype of breast cancer to treat because of its extremely prone to metastasis and the lack of targeted therapy drugs. New purine derivatives were synthesized and evaluated in a series of kinases and cell lines. The most active compounds 3g and 3j were selected based on their antiproliferative activities, then their pharmaceutical activity and mechanism in MDA-MB-231 cells were analyzed. The results in vitro indicated that compounds 3g and 3j can induce MDA-MB-231 cells apoptosis, and inhibit its migration and angiogenesis through influencing protein expression such as Bcl-2, Bax, Bcl-xl, P38, MMP2, MMP9, AKT and EGFR. In vivo results indicate that compounds 3g and 3j can inhibit tumor growth and metastasis and reduce the expression of Ki67 and CD31 protein in TNBC xenograft models. These findings not only broaden our understanding of the anti-TNBC effects and mechanisms of compounds 3g and 3j, but also provide new ideas and reference directions for the treatment of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Apoptose , Purinas/farmacologia , Purinas/uso terapêutico , Proliferação de Células
16.
Eur J Med Chem ; 260: 115723, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37595545

RESUMO

N-acetylneuraminic acid (Neu5Ac) is a glycan receptor of viruses spread in many eukaryotic cells. The present work aimed to design, synthesis and biological evaluation of a panel of Neu5Ac derivatives based on a cyclodextrin (CD) scaffold for targeting influenza and coronavirus membrane proteins. The multivalent Neu5Ac glycoclusters efficiently inhibited chicken erythrocyte agglutination induced by intact influenza virus in a Neu5Ac density-dependent fashion. Compared with inhibition by Neu5Ac, the multivalent inhibitor with 21 Neu5Ac residues on the primary face of the ß-CD scaffold afforded 1788-fold higher binding affinity inhibition for influenza virus hemagglutinin with a dissociation constant (KD) of 3.87 × 10-7 M. It showed moderate binding affinity to influenza virus neuraminidase, but with only about one-thirtieth the potency of that with the HA protein. It also exhibited strong binding affinity to the spike protein of three human coronaviruses (severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2), with KD values in the low micromolar range, which is about 10-time weaker than that of HA. Therefore, these multivalent sialylated CD derivatives have possible therapeutic application as broad-spectrum antiviral entry inhibitors for many viruses by targeting the Neu5Ac of host cells.


Assuntos
COVID-19 , Ciclodextrinas , Inibidores da Fusão de HIV , Influenza Humana , Humanos , Animais , Ácido N-Acetilneuramínico , Antivirais/farmacologia , Galinhas
17.
Eur J Med Chem ; 259: 115662, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37482018

RESUMO

Two series of NSAIDs-EBS derivatives (5a-j and 9a-i) based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and Ebselen moiety were synthesized. Their cytotoxicity was evaluated against five types of human cancer cell lines, BGC-823 (human gastric cancer cell line), SW480 (human colon adenocarcinoma cells), MCF-7 (human breast adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells). Moreover, the most active compound 5j showed IC50 values below 3 µM in all cancer cell lines and with remarkable anticancer activity against MCF-7 (1.5 µM) and HeLa (1.7 µM). The redox properties of the NSAIDs-EBS derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, TrxR1 inhibition activity assay and molecular docking study revealed NSAIDs-EBS derivatives could serve as potential TrxR1 inhibitor.


Assuntos
Adenocarcinoma , Anti-Inflamatórios não Esteroides , Antineoplásicos , Humanos , Antineoplásicos/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia
18.
Eur J Med Chem ; 258: 115536, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37295260

RESUMO

ONS donor ligands L1-L4 were utilized in the preparation of monofunctional dimetallic Ru(η6-arene) complexes (C1-C4). These ONS donor ligand based novel tricoordinated Ru(II) complexes bearing η6-arene co-ligand were prepared for the first time. The current methodology resulted in excellent isolated yields and these complexes were characterized in detail by different spectroscopic and spectrometric techniques. The structures of C1-C2 and C4 were characterized in solid state by single crystal X-ray analysis. The in vitro anticancer analyses showed these novel complexes suppressed the growth of breast (MCF-7), liver (HepG2) and lung (A549) cancer cells. C2 suppressed the growth of these cells in dose-dependent manner revealed form the MTT and crystal violet cell viability assays. Moreover, C2 was observed the most potent complex that was used further in detailed mechanistic analyses in cancer cells. C2 showed good cytotoxic activity at 10 µM dose level as compared to cisplatin or oxaliplatin in these cancer cells. We observed morphological changes in cancer cells upon treatment with C2. Moreover, C2 suppressed the invasion and migration ability of cancer cells. C2 induced cellular senescence to retard cell growth and suppressed the formation of cancer stem cells. Importantly, C2 showed synergistic anticancer effect in combination with cisplatin and Vitamin C to further inhibit cell growth which suggested the potential role of C2 in cancer therapy. Mechanistically, C2 inhibited NOTCH1 dependent signaling pathway to suppress cancer cell invasion, migration and cancer stem cells formation. Thus, these data suggested potential role of C2 in cancer therapy by targeting NOTCH1-dependent signaling to suppress tumorigenesis. The results obtained in this study for these novel monofunctional dimetallic Ru(η6-arene) complexes showed their high anticancer potency and this study will pave to further cytotoxicity exploration on this class of complexes.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Cisplatino/farmacologia , Ácido Ascórbico/farmacologia , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/química , Transdução de Sinais , Rutênio/farmacologia , Rutênio/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais
19.
J Colloid Interface Sci ; 647: 384-394, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37269735

RESUMO

HYPOTHESIS: Stimulus-responsive microemulsions have aroused significant attention because of their versatile and reversible switchability between stable and unstable states. However, most stimuli-responsive microemulsions are based on stimuli-responsive surfactants. We posit that the change in the hydrophilicity of a selenium-containing alcohol triggered by a mild redox reaction could also influence the stability of microemulsions and provide a new nanoplatform for the delivery of bioactive substances. EXPERIMENTS: A selenium-containing diol (3,3'-selenobis(propan-1-ol), PSeP) was designed and used as a co-surfactant in a microemulsion with ethoxylated hydrogenated castor oil (HCO40), diethylene glycol monohexyl ether (DGME), 2-n-octyl-1-dodecanol (ODD) and water. The redox-induced transition in PSeP was characterized by 1H NMR, 77Se NMR, and MS. The redox-responsiveness of the ODD/HCO40/DGME/PSeP/water microemulsion was investigated through determination of a pseudo-ternary phase diagram, analysis by dynamic light scattering, and electrical conductivity, and its encapsulation performance was evaluated by determination of the solubility, stability, antioxidant activity, and skin penetrability of encapsulated curcumin. FINDINGS: The redox conversion of PSeP enabled efficient switching of ODD/HCO40/DGME/PSeP/water microemulsions. Addition of oxidant (H2O2), oxidized PSeP into more hydrophilic PSeP-Ox (selenoxide), disrupting the emulsifying capacity of the combination of HCO40/DGME/PSeP, markedly reducing the monophasic microemulsion region in the phase diagram, and inducing phase separation in some formulations. Addition of reductant (N2H4·H2O), reduced PSeP-Ox and restored the emulsifying capacity of the combination of HCO40/DGME/PSeP. In addition, PSeP-based microemulsions can significantly enhance the solubility in oil (by 23 times), stability, antioxidant capacity (DPPH∙ radical scavenging by 91.74 %), and skin penetrability of curcumin, showing clear potential for encapsulation and delivery of curcumin and other bioactive substances.

20.
Carbohydr Polym ; 312: 120770, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37059526

RESUMO

Treating wastewater containing malachite green (MG) using porous materials with both adsorption and degradation functions have become a major challenge in achieving the carbon neutrality goal. Herein by incorporating the ferrocene (Fc) group as a Fenton active center, a novel composite porous material (DFc-CS-PEI) was prepared using chitosan (CS) and polyethyleneimine (PEI) as skeletons and oxidized dextran as a crosslinker. DFc-CS-PEI not only possesses satisfactory adsorption performance to MG but also excellent degradability in the presence of a minor amount of H2O2 (3.5 mmol/L) without any additional assistance, due to high specific surface area and active Fc group. The maximum adsorption capacity is ca. 177.73 ± 3.11 mg/g, outperforming most CS-based adsorbents. The removal efficiency of MG is significantly enhanced from 20 % to 90 % as DFc-CS-PEI and H2O2 coexist, due to ·OH-dominated Fenton reaction, and remained in a wide pH range (2.0-7.0). Cl- exhibits notable suppression on the degradation of MG because of quenching effects. Note that DFc-CS-PEI has a very small iron leaching (0.2 ± 0.015 mg/L), and can be rapidly recycled by simple water-washing, without any harmful chemicals and potential second pollution. Such versatility, high stability, and green recyclability make the as-prepared DFc-CS-PEI a promising porous material for the treatment of organic wastewater.

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