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1.
Dalton Trans ; 49(16): 5192-5204, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32236281

RESUMO

Cycloxygenases (COXs) and matrix metalloproteinases (MMPs) in the tumor microenvironment (TME) are tightly related to the progression of cancers. Here, naproxen as a potent inhibitor of both COX and MMP was combined with platinum(iv) to construct hybrids as antitumor agents. Compound 2 with comparable or even superior activities to that of cisplatin, oxaliplatin, and carboplatin, great potential for reversing drug resistance, and superior tumor targeting properties was screened out as a lead compound. Moreover, compound 2 possessed potent tumor growth inhibition capability in vivo, which was comparable to that of oxaliplatin, and displayed rather lower side effects than the platinum(ii) reference drugs. The naproxen platinum(iv) complex could easily undergo reduction and liberate the platinum(ii) complex and naproxen as well as exert a multifunctional antitumor mechanism: (i) the liberated platinum(ii) fragment would cause serious DNA injury; (ii) naproxen would inhibit COX-2 and decrease tumor-associated inflammation; and (iii) the naproxen platinum(iv) complex exhibited remarkable MMP-9 inhibition in tumor tissues. These antitumor functions can help reduce the growth and metastasis of malignancy.

2.
Eur J Pharm Sci ; 148: 105319, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32205231

RESUMO

As one of the most promising drug delivery carriers, self-assembled DNA nanostructures are characterized of well-defined sizes, excellent biocompatibility, high drug loading and ability to control drug release. Studying the interactions between anticancer drugs and DNA nanostructures can help to associate microstructure-drug loading-release rate-therapeutic effect. Herein AS1411 aptamer-tethered DNA nanotrains (AS1411NTrs) were constructed and used as anthracyclines carrier with high payload for targeted delivery. The bindings of doxorubicin (DOX), epirubicin (EPI), and daunorubicin (DAU) to AS1411NTrs were investigated by isothermal titration calorimetry and fluorescence spectroscopy, and thermodynamic parameters were obtained. The high drug payload capacity of AS1411NTrs was verified by the large number of binding sites (~20). The binding mode was determined by differential scanning calorimetry and potassium iodide (KI) quenching experiments. The release experiment data showed that DNase I facilitated drug release and the release followed the first-order kinetic model. MTT cell viability assay demonstrated that the drug-loaded AS1411NTrs had significantly higher cytotoxicity against target HeLa cells than normal human liver L02 cells. These findings revealed that AS1411NTrs had high payload and targeted release capacity for DOX, EPI, and DAU. This result can provide a theoretical basis for constructing reasonable DNA nanostructures based on drug carriers.

3.
Int J Nanomedicine ; 14: 8665-8683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806963

RESUMO

Background: The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy. Purpose: The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy. Methods: Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs). Results: The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about -29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups. Conclusion: Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.

4.
Food Funct ; 10(12): 8182-8194, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31696185

RESUMO

Natural polyphenols showing a variety of beneficial effects will interact with multiple proteases after administration. The interactions of oxyresveratrol and piceatannol with trypsin and lysozyme were investigated using fluorescence spectroscopy, UV-vis absorption spectroscopy, circular dichroism spectroscopy, differential scanning calorimetry and molecular docking. Fluorescence quenching results and UV-vis absorption difference spectra revealed that the quenching process was a static mode initiated by ground-state complex formation. The different binding ability of oxyresveratrol and piceatannol with trypsin and lysozyme was discussed based on their different molecular structures. Moreover, the major driving force for the binding process was elucidated as hydrogen bonding and van der Waals forces by the negative enthalpy and entropy changes. Synchronous fluorescence, three-dimensional fluorescence and circular dichroism spectral analysis suggested that the binding of oxyresveratrol and piceatannol to trypsin and lysozyme induced some microenvironmental and conformational changes of the two enzymes. The thermal stability of the enzymes in the presence of polyphenols was studied based on the change in melting temperature by differential scanning calorimetry. The above experimental results were validated by the protein-ligand docking studies which showed the location of the two ligands in the enzymes and the surrounding amino acid residues. Furthermore, enzyme activity assays indicated that the enzymatic activity of trypsin and lysozyme was inhibited by oxyresveratrol and piceatannol. The effect of trypsin and lysozyme on the antioxidant activity and stability of oxyresveratrol and piceatannol was also investigated. In conclusion, the comparative study on the interaction of oxyresveratrol and piceatannol with trypsin and lysozyme showed that the positions of hydroxyl groups of the polyphenols had an important influence on their interaction with enzymes and their antioxidant activity and stability as well as the enzyme activities. The obtained results are expected to provide a theoretical basis for the application of polyphenols in functional foods and pharmaceuticals.

5.
Dalton Trans ; 48(42): 16000-16007, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31595898

RESUMO

Nickel phosphides are considered to be a promising lithium storage host due to their high theoretical capacities. However, the volume change during the charge-discharge process and inherent poor reaction kinetics limit their electrochemical performance. To solve these problems, Ni/Ni2P heterostructures encapsulated in 3D porous carbon networks are fabricated. The macro/micro-pores-rich carbon networks are in situ constructed via a freeze-drying method and subsequent pyrolysis route using NaCl as a template. In the following phosphorization process, Ni/Ni2P nanoparticles are homogenously embedded in the carbon matrix. When used as anodes for lithium ion batteries, the Ni/Ni2P/porous carbon networks deliver high discharge capacity, good cycling stability as well as good rate performance. It is believed that metallic Ni and porous carbon networks significantly improve the conductivity of electrodes. Moreover, the 3D conductive matrix can not only alleviate the volume change, but also prevent the aggregation and pulverization of Ni2P nanoparticles during the charge-discharge process.

6.
Bioorg Med Chem Lett ; 29(20): 126670, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31500997

RESUMO

A new aminonaphthalimide platinum(IV) complex was developed by incorporating aminonaphthalimide, a DNA intercalator, into the platinum(IV) system. This complex displayed potent antitumor activities against all tested tumor cell lines in vitro and showed great potential in overcoming drug resistance of cisplatin. Moreover, it remarkably inhibited the growth of CT26 xenografts in BALB/c mice without severe side effects in vivo. Then, the compound exhibited a dual DNA damage antitumor mechanism that it could interact with DNA in tetravalent form via the naphthalimide group to cause DNA lesion, and the further liberation of platinum(II) complex after reduction would induce remarkable secondary damage to DNA. Meanwhile, it caused cell apoptosis through an intrinsic apoptosis pathway by up-regulating the expression of caspase 3 and caspase 9.

7.
Bioorg Med Chem ; 27(10): 2112-2121, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30981607

RESUMO

A series of bi-functional 7-hydroxycoumarin platinum(IV) complexes were synthesized, characterized, and evaluated for antitumor activities. The 7-hydroxycoumarin platinum(IV) complexes display moderate to effective antitumor activities toward the tested cell lines and show much potential in overcoming drug resistance of platinum(II) drugs. In reducing microenvironment, the title compounds could be reduced to platinum(II) complex accompanied with two equivalents of coumarin units. By a unique mechanism, the 7-hydroxycoumarin platinum(IV) complex attacks DNA via the released platinum(II) compound, meanwhile it also inhibits the activities of cyclooxygenase by coumarin fragment. This action mechanism might be of much benefit for reducing tumor-related inflammation in the progress of inhibiting tumor proliferation and overcoming cisplatin resistance. The incorporation of 7-hydroxycoumarin leads to significantly enhanced platinum accumulation in both whole tumor cells and DNA. The HSA interaction investigation reveals that the tested coumarin platinum(IV) compound could effectively combine with HSA via van der Waals force and hydrogen bond.


Assuntos
Antineoplásicos/síntese química , Complexos de Coordenação/síntese química , Platina/química , Umbeliferonas/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Dano ao DNA/efeitos dos fármacos , Humanos , Ligação Proteica , Albumina Sérica/química , Albumina Sérica/metabolismo
8.
Bioresour Technol ; 282: 179-188, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30861447

RESUMO

Continuous stirred-tank digesters with tetracyclines and sulfonamides were operated to investigate the impacts of antibiotic pressure on sludge anaerobic digestion. The versatile methanogen Methanosarcinales and strictly hydrogenotrophic methanogen Methanobacteriales increased and decreased by 21.1% and 10.9% under antibiotic pressure, respectively. KEGG analysis revealed that hydrogenotrophic and acetoclastic methanogenesis pathways were all affected. The decrease in abundance of function genes involved in lipid metabolism, carbohydrate metabolism, and fatty acid degradation, would lead to a reduction in methane production by 25%. Network analysis indicated positive associations among tetracycline residuals, abundance of resistance genes (ARGs), and specific member of potential hosts. Over 1000 ARG subtypes were widely detected in sludge, including macrolide (28%), tetracycline (24%), fluoroquinolone (20%), and peptide (20%) resistance genes. AD process exposed to long-term antibiotic would increase the diversity and abundance of ARG, enhance the association of ARG with specific microbes, and select bacteria able to perform chemotaxis mechanism.


Assuntos
Antibacterianos/farmacologia , Metagenômica , Esgotos/microbiologia , Tetraciclina/farmacologia , Anaerobiose , Farmacorresistência Bacteriana/efeitos dos fármacos , Methanosarcinales/efeitos dos fármacos , Fatores de Risco
9.
J Inorg Biochem ; 194: 34-43, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826588

RESUMO

A series of new 4-hydroxycoumarin platinum(IV) complexes were designed, synthesized and evaluated as antitumor agents. All the title compounds display moderate to effective antitumor activities toward the tested cell lines and two prominent compounds were screened out with activities comparable to cisplatin and oxaliplatin. The mechanism investigation demonstrates that the platinum(IV) compounds could be reduced to bivalence and exert significant genotoxicity to tumor cells. Meanwhile the coumarin moiety endows the title compounds with cyclooxygenase inhibitory competence which might favour the reduction of tumor-related inflammation and further influence tumor proliferation. The coumarin platinum(IV) complex could effectively induce apoptosis of SKOV-3 cells through up-regulating the expression of caspase3 and caspase9. Furthermore, the conversion of platinum(II) drugs to platinum(IV) form via the conjunction with 4-hydroxycoumarin enhances the drug uptake in whole cells and DNA simultaneously. Moreover, the 4-hydroxycoumarin platinum(IV) complex could combine with human serum albumin via van der Waals force and hydrogen bond, which would influence their transport and bioactivities in vivo.

10.
Bioresour Technol ; 276: 51-59, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30611086

RESUMO

This study established two mesophilic anaerobic digesters to ascertain the microbial dynamics and variation characteristics of antibiotic resistance genes (ARGs) during sludge anaerobic digestion (AD) with high concentration of antibiotics. System parameters, microbial community, ARGs (tetA, tetM, tetW, sulI, sulII) and integrase gene of class 1 (intI1) were analyzed. General performance of AD showed methane production was inhibited by 17.1% under the pressure of antibiotics. Microbial 16S rRNA high-throughput sequencing results showed the richness of microbial community decreased, but a higher diversity was found with antibiotics added. Furthermore, microbial community structure at genus level was significantly changed. Real-time quantitative PCR of several target genes demonstrated that the adjunction of high concentration of antibiotics exerted a significant induction influence on ARGs, however, the abundance of intI1 decreased observably. Correlation analysis showed intI1 only played a small role in ARGs' transfer during AD, change of potential hosts was the key factor instead.


Assuntos
Antibacterianos/metabolismo , Resistência Microbiana a Medicamentos , Microbiota , Esgotos , Sulfonamidas/metabolismo , Tetraciclinas/metabolismo , Anaerobiose , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Microbiota/efeitos dos fármacos , RNA Ribossômico 16S/genética , Sulfonamidas/farmacologia , Tetraciclinas/farmacologia
11.
Immunology ; 157(1): 13-20, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681737

RESUMO

Interleukin-35 (IL-35) is a recently identified heterodimeric cytokine in the IL-12 family. It consists of an IL-12 subunit α chain (P35) and IL-27 subunit Epstein-Barr virus-induced gene 3 (EBI3) ß chain. Unlike the other IL-12 family members, it signals through four unconventional receptors: IL-12Rß2-IL-27Rα, IL-12Rß2-IL-12Rß2, IL-12Rß2-GP130, and GP130-GP130. Interleukin-35 signaling is mainly carried out through the signal transducer and activator of transcription family of proteins. It is secreted not only by regulatory T (Treg) cells, but also by CD8+ Treg cells, activated dendritic cells and regulatory B cells. It exhibits immunosuppressive functions distinct from those of other members of the IL-12 family; these are mediated primarily by the inhibition of T helper type 17 cell differentiation and promotion of Treg cell proliferation. Interleukin-35 plays a critical role in several immune-associated diseases, such as autoimmune diseases and viral and bacterial infections, as well as in tumors. In this review, we summarize the structure and function of IL-35, describe its role in immune-related disorders, and discuss the mechanisms by which it regulates the development and progression of diseases, including inflammatory bowel disease, collagen-induced arthritis, allergic airway disease, hepatitis, and tumors. The recent research on IL-35, combined with improved techniques of studying receptors and signal transduction pathways, allows for consideration of IL-35 as a novel immunotherapy target.


Assuntos
Doenças do Sistema Imunitário/metabolismo , Imunoterapia/métodos , Subunidade p35 da Interleucina-12/metabolismo , Interleucinas/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Autoimunidade , Humanos , Subunidade p35 da Interleucina-12/genética , Interleucinas/genética , Ativação Linfocitária , Antígenos de Histocompatibilidade Menor/genética , Transdução de Sinais
12.
ACS Appl Mater Interfaces ; 10(42): 35994-36001, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30265508

RESUMO

Three-dimensional honeycomb-like carbon network-encapsulated Fe/Fe3C/Fe3O4 composites are constructed via a facile pyrolysis of ferrite nitrate-poly(vinyl pyrrolidone) precursors. The nanostructures of the composites form in terms of the iron catalysis in the pyrolysis process, which greatly depends on the reaction temperature and contents of raw materials. The Fe/Fe3C/Fe3O4/C composite obtained at 700 °C possesses a high surface area, outstanding structural stability, and fast electron/Li ion transportability. As the anode for lithium-ion batteries, it displays a high specific capacity (1295 mAh g-1 at 0.2 A g-1), long cycling stability, and fast kinetics (345 mAh g-1 after 500 cycles at 5 A g-1). Besides the nanostructures, the marriage of different components also contributes to the superior electrochemical performance. The integral carbon matrix supplies a fast electron/Li transportation pathway. Fe/Fe3C acts as an electrocatalyst in the electrode, which may bring extra capacity. The satisfied performance and facile fabrication with low cost make it a competitive material in practical applications.

13.
Eur J Pharm Sci ; 124: 127-136, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153524

RESUMO

Naphthalimide platinum(IV) antitumor complexes with potential dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The incorporation of DNA targeted naphthalimide group to the platinum(IV) system exerts much positive impacts on their antitumor efficacy. The mechanism research reveals that the title compounds could interact with dsDNA in platinum(IV) form via the naphthalimide group and cause DNA lesion. The further reduction would release platinum(II) complexes and naphthalimide acids which would induce remarkable secondary damage to DNA. Furthermore, the naphthalimide platinum(IV) compounds could combine with human serum albumin via electrostatic force, which are favourable for their storage and transport in blood. Moreover, the title compounds exhibit higher accumulation in tumor cells, and exert lower toxic and higher safe properties than oxaliplatin in vivo.


Assuntos
Antineoplásicos/farmacologia , Naftalimidas/farmacologia , Compostos Organoplatínicos/farmacologia , Linhagem Celular Tumoral , Dano ao DNA , Humanos
14.
Sci Total Environ ; 612: 788-798, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28866406

RESUMO

Spread of antibiotic resistance genes (ARGs) originating from sewage sludge is highlighted as an eminent health threat. This study established a thermophilic anaerobic digester using one-step startup strategy to quickly remove tetracycline and sulfonamides resistance genes from sewage sludge. At least 20days were saved in the startup period from mesophilic to thermophilic condition. Based on the results of 16S rDNA amplicons sequencing and predicted metagenomic method, the successful startup largely relied on the fast colonization of core thermophilic microbial population (e.g. Firmicutes, Proteobacteria, Actinobacteria). Microbial metabolic gene pathways for substrate degradation and methane production was also increased by one-step mode. In addition, real-time quantitative PCR approach revealed that most targeted tetracycline and sulfonamides resistance genes ARGs (sulI, tetA, tetO, tetX) were substantially removed during thermophilic digestion (removal efficiency>80%). Network analysis showed that the elimination of ARGs was attributed to the decline of their horizontal (intI1 item) and vertical (potential hosts) transfer-related elements under high-temperature. This research demonstrated that rapid startup thermophilic anaerobic digestion of wastewater solids would be a suitable technology for reducing quantities of various ARGs.


Assuntos
Bactérias/genética , Reatores Biológicos , Genes Bacterianos , Esgotos/microbiologia , Anaerobiose , Antibacterianos , Antiporters/genética , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Resistência Microbiana a Medicamentos/genética , Sulfonamidas , Tetraciclina , Eliminação de Resíduos Líquidos
15.
BMC Neurol ; 17(1): 128, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28673282

RESUMO

BACKGROUND: The purpose of this study was to investigate the therapeutic effects and mechanisms of hyperbaric oxygen (HBO) treatment on rats following spinal cord injury (SCI). METHODS: A total of 45 Sprague-Dawley (SD) rats were randomly divided into three groups. Sham-SCI group was surgically exposed but not subjected to the SCI procedure. SCI-control group was administered SCI and treated with regular air. SCI-HBO group was administered SCI and HBO treatment. Neuromotor functions were examined using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and the inclined plane assessment at before SCI (baseline) and after SCI. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured. RESULTS: Starting from Day 1 after SCI but except Day 2, the SCI-HBO group has significantly higher BBB scores than the SCI-control group. After SCI, the maximum inclination angles at which rats could maintain were significantly lower in both SCI groups. But the maximum angles were significantly bigger for the rats in the SCI-HBO group than those on the SCI-control group at 5, 10 and 20 days after SCI. SOD activities in SCI-HBO rats were significantly higher and MDA levels were significantly lower than in SCI-control rats, at two and five days after SCI. There was also less cystic degeneration of spinal cord in SCI-HBO rats, compared to SCI-control rats. CONCLUSIONS: These results suggest that HBO treatment has a therapeutic value in treating SCI. Increased oxygen free radical scavenging and reduced lipid oxidation may be one of the mechanisms.


Assuntos
Oxigenação Hiperbárica/métodos , Traumatismos da Medula Espinal/terapia , Medula Espinal/patologia , Animais , Feminino , Ratos , Ratos Sprague-Dawley
16.
J Med Chem ; 60(13): 5736-5748, 2017 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-28603992

RESUMO

Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo. Galactoside Pt(IV), glucoside Pt(IV), and mannoside Pt(IV) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(IV) complexes 5, 6, 7, and 8 (IC50 0.24-3.97 µM) had better antitumor activity of nearly 166-fold higher than the positive controls cisplatin (1a), oxaliplatin (3a), and satraplatin (5a). The presence of a hexadecanoic chain allowed binding with human serum albumin (HSA) for drug delivery, which not only enhanced the stability of the inert platinum(IV) prodrugs but also decreased their reduction by reductants present in human whole blood. Their preferential accumulation in cancer cells compared to noncancerous cells (293T and 3T3 cells) suggested that they were potentially safe for clinical therapeutic use.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Glicosilação , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/metabolismo , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Albumina Sérica/metabolismo
17.
Dalton Trans ; 45(29): 11830-8, 2016 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-27373800

RESUMO

Conjugates (A1-A5) of the Pt(iv) derivative (A6) with amino groups from peracetyl glucose, rhamnose and mannose with a propyl amino or ethyl amino linker at the reducing end were synthesized and exhibited significant therapeutic efficacy in tumour cells, especially for prostate cancer (PCa). The antitumor activities are greatly affected by glycosyl groups. Cytotoxic experiments in vitro indicated that the antitumor activities were increased by 5-fold when its Pt(iv) derivative was conjugated to S18 (IC50 = 4.82 ± 0.45 µM) and by 12-fold when conjugated to S21 (IC50 = 1.9 ± 0.67 µM). The mannose substituted Pt(iv) complexes A4 and A5 were also over an order of magnitude more potent towards HeLa, A549, MCF-7 and PC3 than cisplatin and oxaliplatin. Importantly, the glycosylated Pt(iv) derivatives A4 and A5 displayed potential safety for clinical therapeutic exposure with IC50 of 84 µM and 169 µM compared with cisplatin (IC50 = 8 µM) to 3T3. Cellular uptake and DNA platination are higher than cisplatin and oxaliplatin. ESI-MS analysis of A5 binding to 5'-dGMP revealed that bifunctional DNA lesions were formed. The antitumor activities in vivo showed that the MTD and LD50 for A4 and A5 are nearly 4-fold higher than that of oxaliplatin indicating the potential safety for the glycosylated Pt(iv) complexes.


Assuntos
Antineoplásicos , Platina , Pró-Fármacos , Células 3T3 , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Glicosilação , Humanos , Dose Letal Mediana , Dose Máxima Tolerável , Camundongos , Platina/química , Platina/farmacologia , Platina/uso terapêutico , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
18.
Dalton Trans ; 45(25): 10366-74, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27252024

RESUMO

A new series of glycosylated Pt(iv) complexes were designed, synthesized and evaluated for antitumor activities in vitro and in vivo. The incorporation of glycosyl groups to the Pt(iv) system has much influence on the antitumor abilities. Four lead compounds with activities comparable or even superior to cisplatin and oxaliplatin are screened out. These Pt(iv) complexes could be reduced to release Pt(ii) complexes and cause the death of tumour cells. The apoptosis-inducing properties of these compounds are similar to cisplatin. The accumulation of the glycosylated Pt(iv) complexes in cells and DNA is higher than cisplatin and oxaliplatin. The in vivo assay demonstrates that the tested compounds inhibit the growth of HepG2 tumors with low toxicity.


Assuntos
Antineoplásicos , Desenho de Fármacos , Hexoses/química , Compostos Organoplatínicos , Platina/química , Ramnose/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , DNA/efeitos dos fármacos , Glicosilação , Células Hep G2 , Humanos , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Oxaliplatina
19.
J Agric Food Chem ; 63(14): 3734-41, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25804187

RESUMO

Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive structure-activity relationship study screens four effective compounds, including thaxtomin A and thaxtomin C. It is indicated that 4-nitro indole fragment is essential for phytotoxicity, while benzyl and m-hydroxybenzyl substituents on the diketopiperazine ring are favorable for the efficacy. The N-methylations on indole and diketopiperazine show weak influence on the herbicidal activities. The four selected compounds show effective herbicidal activities against Brassica campestris, Amaranthus retroflexus, and Abutilon theophrasti, which are comparable or better than dichlobenil, even at a dosage of 187.5 g ha(-1). Moreover, these four compounds show good crop-selective properties to different crops and exhibit moderate protoporphyrinogen oxidase (PPO) enzyme inhibition. The antifungal results indicate that thaxtomin C displays inhibition to a wide range of fungi.


Assuntos
Herbicidas/síntese química , Herbicidas/farmacologia , Indóis/síntese química , Indóis/farmacologia , Piperazinas/síntese química , Piperazinas/farmacologia , Plantas Daninhas/efeitos dos fármacos , Herbicidas/química , Indóis/química , Estrutura Molecular , Piperazinas/química , Relação Estrutura-Atividade , Controle de Plantas Daninhas
20.
Nanoscale Res Lett ; 9(1): 590, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25364317

RESUMO

In this study, titanium nitride (TiN) is synthesized using reactive sputtering for a self-aligned gate process. The Schottky barrier height of the TiN on n-GaN is around 0.5 to 0.6 eV and remains virtually constant with varying nitrogen ratios. As compared with the conventional Ni electrode, the TiN electrode presents a lower turn-on voltage, while its reverse leakage current is comparable with that of Ni. The results of annealing evaluation at different temperatures and duration times show that the TiN/W/Au gate stack can withstand the ohmic annealing process at 800°C for 1 or 3 min. Finally, the self-aligned TiN-gated AlGaN/GaN heterostructure field-effect transistors are obtained with good pinch-off characteristics.

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