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1.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 26-37, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31889181

RESUMO

Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Bases de Schiff/toxicidade , Bases de Schiff/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofenóis/química , Dinoprostona/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Feminino , Fibroblastos/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Testes de Função Renal , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
2.
Acta Crystallogr C Struct Chem ; 76(Pt 1): 44-63, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31919307

RESUMO

Eight novel Schiff bases derived from benzil dihydrazone (BDH) or benzil monohydrazone (BMH) and four fused-ring carbonyl compounds (3-formylindole, FI; 3-acetylindole, AI; 3-formyl-1-methylindole, MFI; 1-formylnaphthalene, FN) were synthesized and characterized by elemental analysis, ESI-QTOF-MS, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. They are (1Z,2Z)-1,2-bis{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFI), C32H24N6, (1Z,2Z)-1,2-bis{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethane (BDHAI), C34H28N6, (1Z,2Z)-1,2-bis{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BMHMFI) acetonitrile hemisolvate, C34H28N6·0.5CH3CN, (1Z,2Z)-1,2-bis{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFN), C36H26N4, (Z)-2-{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFI), C23H17N3O, (Z)-2-{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethanone (BMHAI), C24H19N3O, (Z)-2-{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHMFI), C24H19N3O, and (Z)-2-{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFN) C25H18N2O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four (BDHMFI, BDHFN, BMHMFI and BMHFN) are inactive and the other four (BDHFI, BDHAI, BMHFI and BMHAI) show severe toxicities against human A549 and mouse 4T1 cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex-dock function in SYBYL-X 2.0 software. Three target proteins, i.e. human ether-á-go-go-related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1, were chosen as the targets. Finally, the ligand-based structure-activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.


Assuntos
Proliferação de Células/efeitos dos fármacos , Fenilglioxal/análogos & derivados , Bases de Schiff/química , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Células NIH 3T3 , Fenilglioxal/química , Fenilglioxal/farmacologia , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
3.
Food Chem ; 302: 125336, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419772

RESUMO

This study reports a stepwise optimization of switchable liquid-liquid microextraction (SLLME) for cobalt determination by flame atomic absorption spectrometry (FAAS) coupled with a slotted quartz tube (SQT). The main purpose of this study was to develop an accurate and sensitive analytical method for cobalt. Extraction method was used to separate and preconcentrate cobalt from sage tea and vitamin B12 samples after complexing with a Schiff base ligand. 107.7 folds enhancement in detection power under the optimum conditions was recorded with respect to direct FAAS. This enhancement correlated to 3.1 µg/L limit of detection and 10 µg/L limit of quantification. The SLLME-SQT-FAAS method was linear over a broad concentration range and low %RSD values established high precision for the method. Appreciable percent recovery results (94-108%) obtained from spiked sage sample and from cobalamin also validated the accuracy of the method.


Assuntos
Cobalto/análise , Microextração em Fase Líquida/métodos , Espectrofotometria Atômica/métodos , Chás de Ervas/análise , Vitamina B 12/análise , Limite de Detecção , Quartzo , Reprodutibilidade dos Testes , Salvia officinalis/química , Bases de Schiff/química , Espectrofotometria Atômica/instrumentação , Vitamina B 12/química
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117389, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31377683

RESUMO

Rational design chelating fluorescent sensors probing metal ions in biological system are continuously hot essays nowadays, especially for zinc detection. Herein, a naphthylideneimine based zinc fluorescence probe (3) was prepared and characterized in this work. Structural features and optical properties of 3 and its metallic complexes were characterized. Fluorescent experiment indicates 3 is extremely sensitive and selective for Zn2+ with a strong fluorescence enhancement (∼34 folds) in aqueous buffer solution with a limit of detection (LOD) of 3.78 × 10-7 mol L-1. Formation constant (logKa) of the chelating complex of 3 and Zn2+ ion was determined to be 4.45. Theoretical studies were carried out to get deep insight into the response mechanism in the sensing process. Density functional theory (DFT) methods calculated formation Gibbs free energy (ΔrGmÓ©) of the deprotonated complexes model (32- ⊃ Zn) is -2.9 kcal/mol, which is in good agreement with the experimental result. The calculation results show that the low excitation states can be ascribe to S0 → T2 and S0 → S1 at 390-430 nm and 310-330 nm, respectively, due to the π → π∗ transition. Finally, yeast cell imaging experiments indicate that 3 can monitor intracellular Zn2+ as well. These findings would enable this fluorescent probe to be used as a Zinc sensor.


Assuntos
Corantes Fluorescentes/química , Naftalenos/química , Bases de Schiff/química , Espectrometria de Fluorescência/métodos , Zinco/análise , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/química
5.
Eur J Med Chem ; 185: 111780, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655429

RESUMO

Two new series of pyrrolizine-5-carboxamides were synthesized and evaluated for their anticancer and anti-inflammatory activities. The new compounds exhibited potent cytotoxicity (IC50 = 0.10-22.96 µM) against three cancer (MCF-7, A2780 and HT29) cell lines with selectivity index in the range of 1-258. Moreover, these compounds also exhibited significant anti-inflammatory activity (18.13-44.51% inhibition of inflammation) mediated by inhibition of COX-1/2 with preferential inhibition of COX-2. The study of SAR revealed favorable cytotoxic outcomes of the aliphatic side chain and 4-thiazolidinone moiety at C6 of the pyrrolizine nucleus, while anti-inflammatory activities was improved with the (hetero)aromatic substituents. The IC50 values which inhibit COX-2 were higher than those needed to inhibit the growth of cancer cell lines. Mechanistic studies also revealed inhibition of multiple kinases by compounds 12, 19 and 22. Moreover, compounds 12, 14, 16 and 22 induced cell cycle arrest and apoptosis in MCF-7 cells. Docking studies revealed nice fitting of the new compounds into COX-1/2. Additionally, compounds 12, 19 and 22 also exhibited higher affinity for CDK2 than CAN508. To sum up, the above-mentioned data highlight these compounds as promising anti-inflammatory and anticancer agents.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Drogas , Edema/tratamento farmacológico , Pirrolidinas/farmacologia , Tiazolidinas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HT29 , Humanos , Células MCF-7 , Masculino , Estrutura Molecular , Pirrolidinas/síntese química , Pirrolidinas/química , Ratos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Tiazolidinas/química
6.
Talanta ; 207: 120321, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594568

RESUMO

An optical aptasensor-based sensing platform for rapid insulin detection was fabricated. Aminated porous silica microparticles (PSiMPs) were synthesized via a facile mini-emulsion method to provide large surface area for covalent immobilization of insulin-binding DNA aptamer (IGA3) by glutaraldehyde cross-linking protocol. A Nickel-salphen type complex with piperidine side chain [Ni(II)-SP] was synthesized with a simple one-pot reaction, and functionalized as an optical label due to strong π-π interaction between aromatic carbons of G-quadruplex DNA aptamer and planar aromatic groups of Ni(II)-SP to form the immobilized IGA3-Ni(II)-SP complex, i.e. the dye-labeled aptamer, thereby bringing yellow colouration to the immobilized G-quartet plane. Optical characterization of aptasensor towards insulin binding was carried out with a fiber optic reflectance spectrophotometer. The maximum reflectance intensity of the immobilized IGA3-Ni(II)-SP complex at 656 nm decreased upon binding with insulin as aptasensor changed to brownish orange colouration in the background. This allows optical detection of insulin as the colour change of aptasensor is dependent on the insulin concentration. The linear detection range of the aptasensor is obtained from 10 to 50 µIU mL-1 (R2 = 0.9757), which conformed to the normal fasting insulin levels in human with a limit of detection (LOD) at 3.71 µIU mL-1. The aptasensor showed fast response time of 40 min and long shelf life stability of >3 weeks. Insulin detection using healthy human serums with informed consent provided by participants suggests the DNA aptamer biosensor was in good agreement with ELISA standard method using BIOMATIK Human INS (Insulin) ELISA Kit.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/instrumentação , Insulina/análise , Dispositivos Ópticos , Compostos Organometálicos/química , Fenilenodiaminas/química , Aptâmeros de Nucleotídeos/química , Ensaio de Imunoadsorção Enzimática , Humanos , Concentração de Íons de Hidrogênio , Insulina/sangue , Insulina/química , Insulina/metabolismo , Limite de Detecção , Porosidade , Bases de Schiff/química , Dióxido de Silício/química , Fatores de Tempo
7.
Anticancer Res ; 39(12): 6693-6699, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810934

RESUMO

BACKGROUND/AIM: Melanoma represents a big challenge for clinical treatment. Besides being the most aggressive and the deadliest form of skin cancer, it is often refractory to commonly used anticancer drugs. Hence, developing new anti-cancer agents is crucial to improve refractory melanoma treatment. Studies using palladium(II) complexes have reported antitumor effects on cancer cells. In this study, we aimed to determine the cytotoxic effect of three novel synthesized Pd(II) complexes with Schiff bases derived from 4-aminoacetophenone on the MDA-MB-435 melanoma cell line. MATERIALS AND METHODS: Cells were treated with ligand and Pd(II) complexes. Cell viability, morphology and death induction upon treatment were examined. RESULTS: Novel synthesized Pd(II) complexes led to decreased viability of cells. They also induced morphological alterations and cell death, mainly in the C3 complex. CONCLUSION: The novel synthesized complexes have a significant cytotoxic effect on cell line MDA-MB-435, especially C3 and can be considered as an antitumor agent for further studies.


Assuntos
Acetofenonas/química , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Paládio/uso terapêutico , Bases de Schiff/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/síntese química , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Técnicas In Vitro , Ligantes , Compostos Organometálicos/síntese química , Paládio/química , Rodaminas , Bases de Schiff/química
8.
Top Curr Chem (Cham) ; 377(6): 31, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654245

RESUMO

Cooperative dual catalysis and bifunctional catalysis have emerged as reliable strategies for the development of hitherto difficult asymmetric transformations because they could deliver new reactivity and selectivity, and allow for the employment of substrates not amenable to reaction systems relying on a single, monofunctional catalysts. Furthermore, these modes of catalysis often improve yields and stereoselectivities via the precise recognition and simultaneous activation of nucleophiles and electrophiles. Efforts towards utilizing chiral cationic organic catalysts for asymmetric cooperative catalysis with metal complexes have provided a unique platform to address the challenging issues associated with reaction development. Chiral onium ions, such as tetraalkylammonium, guanidinium, and azolium ions, are employed mainly to control the reactivity and stereochemistry of anionic intermediates through electrostatic and hydrogen-bonding interactions. Metal complexes complement the synergy of the catalysis by activating the substrates via the formation of electrophilic π-allyl complexes, Lewis acid-base adducts, nucleophilic ate complexes, etc. The electrostatic interactions between cations and anions also offer a means to construct complex molecular assemblies, and, thus, onium ions are useful not only for controlling pairing with anionic species, but also for the design of supramolecular catalysts. The combination of onium ions and metal complexes leads to the introduction of novel concepts and powerful strategies for the development of catalysts and chemical transformations.


Assuntos
Ligantes , Metais/química , Carbono/química , Catálise , Cátions/química , Complexos de Coordenação/química , Ácidos de Lewis/química , Bases de Schiff/química , Estereoisomerismo
9.
Carbohydr Polym ; 226: 115256, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582056

RESUMO

In order to improve the antioxidant and antifungal activity of chitosan, eight chitosan derivatives containing Schiff bases and quaternary ammonium salts were synthesized via an intermediate 6-O-chloroacetyl-2-N,N,N-trimethyl quaternary ammonium salt chitosan. Detailed structural characterization was carried out using FTIR and 1H NMR spectroscopy, and elemental analysis. The antifungal activity against F. oxysporum f. sp. cucumerium, B. cinerea, and F. oxysporum f. sp. niveum was evaluated using a mycelium growth rate test. The results indicated that the chitosan derivatives exhibited enhanced antifungal activity when compared to chitosan, especially at 1.0 mg/mL. 6-[4-(2,3-dihydroxyl-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (2.3HBPATC), 6-[4-(2,3,4-trihydroxyl-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (2.3.4HBPATC), 6-[4-(2-fluorine-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (FBPATC), 6-[4-(2-chlorine-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (CBPATC), 6-[4-(2-bromine-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (BBPATC), and 6-[4-(2-hydroxyl-4-chlorine-benzimide) pyridine] acetyl-2-N,N,N-trimethyl-chitosan chloride (HCBPATC) showed inhibitory indices >90.0% at 1.0 mg/mL against F. oxysporum f. sp. cucumerium and B. cinerea. Furthermore, the chitosan derivatives showed stronger antioxidant activity than chitosan, especially 2.3HBPATC and 2.3.4HBPATC with inhibitory indices of 100.0% at 1.6 mg/mL against DPPH and superoxide radicals. Based on these data, it is reasonable to suggest that the introduction of phenolic hydroxyl and halogen groups enhances the antifungal and antioxidant activity of chitosan.


Assuntos
Antifúngicos , Antioxidantes , Botrytis/efeitos dos fármacos , Quitosana/análogos & derivados , Fusarium/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Amônio Quaternário/química , Bases de Schiff/química , Relação Estrutura-Atividade
10.
Molecules ; 24(19)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591309

RESUMO

Ralstonia solanacearum (R. solanacearum)-induced bacterial wilt of the nightshade family causes a great loss in agricultural production annually. Although there has been some efficient pesticides against R. solanacearum, inaccurate pesticide releasing according to the onset time of bacterial wilt during the use of pesticides still hinders the disease management efficiency. Herein, on the basis of the soil pH change during R. solanacearum growth, and pH sensitivity of the Schiff base structure, a pH-sensitive oxidized alginate-based double-crosslinked gel was fabricated as a pesticide carrier. The gel was prepared by crosslinking oxidized sodium alginate (OSA) via adipic dihydrazide (ADH) and Ca2+. After loading tetramycin into the gel, it showed a pH-dependent pesticide releasing behavior and anti-bacterial activity against R. solanacearum. Further study also showed that the inhibition rate of the tetramycin-loaded gel was higher than that of industrial pesticide difenoconazole. This work aimed to reduce the difficulty of pesticide administration in the high incidence period of bacterial wilt and we believe it has a great application potential in nightshade production.


Assuntos
Antibacterianos/administração & dosagem , Macrolídeos/administração & dosagem , Ralstonia solanacearum/efeitos dos fármacos , Adipatos/síntese química , Adipatos/química , Alginatos/química , Alginatos/farmacologia , Antibacterianos/farmacologia , Cálcio/química , Concentração de Íons de Hidrogênio , Macrolídeos/química , Macrolídeos/farmacologia , Praguicidas/farmacologia , Doenças das Plantas/microbiologia , Bases de Schiff/química , Tabaco/efeitos dos fármacos
11.
Dalton Trans ; 48(40): 15220-15230, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31577284

RESUMO

We report 15 new Cu(ii) complexes with tridentate NNO ß-acylenamino ligands derived from 2-picolylamine and bearing up to three alkyl, alkoxy, alkoxycarbonyl, or (pseudo)halide substituents. The structures of nine complexes were elucidated by single crystal X-ray diffraction analysis. Complexes with an unsubstituted pyridine ring crystallised with a square pyramidal coordination sphere, whereas substitution of the pyridine ring led to a square planar coordination sphere around the metal centre. The solution structures and properties of the complexes were characterised by UV-Vis spectroscopy and cyclic voltammetry. They were also tested for their cytotoxic effect on four human cancer cell lines. Two complexes were identified that were highly active with single-digit IC50 values, exceeding those of cisplatin by far. A tentative structure-activity relationship was proposed as well as topoisomerase I inhibition as a possible mode of action, while any significant interference with DNA and the level of reactive oxygen species could be excluded.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Piridinas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/química , DNA Topoisomerases Tipo I/metabolismo , Humanos , Ligantes , Estrutura Molecular , Piridinas/química , Bases de Schiff/química , Soluções , Relação Estrutura-Atividade
12.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640238

RESUMO

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives 6-14. The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were 6 and 14, which exhibited excellent potencies comparable to quinazolinone derivatives 5 and 9, respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety (11a-d). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives (11a-d) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in p-position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.


Assuntos
Antineoplásicos/síntese química , Antioxidantes/síntese química , Quinazolinonas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Células MCF-7 , Estrutura Molecular , Quinazolinonas/química , Quinazolinonas/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Tionas/química
13.
Chemistry ; 25(68): 15594-15608, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31529537

RESUMO

5-(2-Oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) is a natural product formed during bacterial synthesis of vitamin B2. It potently activates mucosal associated invariant T (MAIT) cells and has immunomodulatory, inflammatory, and anticancer properties. This highly polar and unstable compound forms a remarkably stable Schiff base with a lysine residue in major histocompatibility complex class I-related protein (MR1) expressed in antigen-presenting cells. Inspired by the importance of the ribityl moiety of 5-OP-RU for binding to both MR1 and the T cell receptor (TCR) on MAIT cells, each OH was removed in silico. DFT calculations and MD simulations revealed a very stable hydrogen bond between the C3'-OH and uracil N1H, which profoundly restricts flexibility and positioning of each ribityl-OH, potentially impacting their interactions with MR1 and TCR. By using deoxygenation strategies and kinetically controlled imine formation, four monodeoxyribityl and four monohydroxyalkyl analogues of 5-OP-RU were synthesised as new tools for probing T cell activation mechanisms.


Assuntos
Células T Invariáveis Associadas à Mucosa/química , Receptores de Antígenos de Linfócitos T/química , Riboflavina/metabolismo , Bases de Schiff/química , Uracila/química , Simulação por Computador , Humanos , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/genética , Uracila/metabolismo
14.
Mater Sci Eng C Mater Biol Appl ; 105: 110119, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546342

RESUMO

A series of CuII, CoII, ZnII and NiII, complexes of 34,74-dimethyl-12,15,52,55-tetrahydro-2,4,6,8-tetraaza-1,5(2,5)-difurana-3,7(1,2)-dibenzenacyclooctaphane based ligand have been synthesized by template methodology. Characterization of the synthesized complexes has been carried out with the help of various physicochemical and spectroscopic techniques like Infra-Red, ESI-MS, ESR, UV-visible, CHN (elemental analyses), molar conductance, magnetic moment and NMR. Antimicrobial efficacy of the newly designed macrocyclic complexes has performed by the assistance of agar well diffusion method. In-vitro hemolytic and DNA binding studies were also performed in order to analyze or interpret the mode and binding efficiencies as well as the % hemolysis exhibited by the complexes. DFT/TD-DFT studies were carried out in order to elucidate the better insight into the structural parameters. Energy minimization and quantum chemical parameters were calculated using Gaussian09W program.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Animais , Anti-Infecciosos/química , DNA/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Peixes , Hemólise/efeitos dos fármacos , Compostos Macrocíclicos/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Conformação Molecular , Bases de Schiff/química , Espectrofotometria Infravermelho
15.
Molecules ; 24(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500095

RESUMO

Twelve new Schiff base derivatives have been prepared by the condensation reaction of different amino substituted compounds (aniline, pyridin-2-amine, o-toluidine, 2-nitrobenzenamine, 4-aminophenol, and 3-aminopropanol) and substituted aldehydes such as nicotinaldehyde, o,m,p-nitrobenzaldehyde, and picolinaldehyde in ethanol using acetic acid as a catalyst. The envisaged structures of the all the synthesized ligands have been confirmed on the basis of their spectral analysis FT-IR, mass spectroscopy, 1H- and 13C-NMR. In vitro screening of their antibacterial and antifungal potential against Escherichia coli bacterium and Fusarium oxysporum f.sp albedinis (F.o.a) fungus, respectively, revealed that all the ligands showed no significant antibacterial activity, whereas most of them displayed good antifungal activity. Homology modeling and docking analysis were performed to explain the antifungal effect of the most and least active compound against two F.o.a fungus proteins.


Assuntos
Antibacterianos/química , Complexos de Coordenação/química , Escherichia coli/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Aminofenóis/química , Compostos de Anilina/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Escherichia coli/patogenicidade , Fusarium/patogenicidade , Humanos , Ligantes , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Bases de Schiff/química
16.
Molecules ; 24(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480486

RESUMO

Elucidation of the structure and function of biomolecules provides us knowledge that can be transferred into the generation of new materials and eventually applications in e.g., catalysis or bioassays. The main problems, however, concern the complexity of the natural systems and their limited availability, which necessitates utilization of simple biomimetic analogues that are, to a certain degree, similar in terms of structure and thus behaviour. We have, therefore, devised a small library of six tridentate N-heterocyclic coordinating agents (L1-L6), which, upon complexation, form two groups of artificial, monometallic non-heme iron species. Utilization of iron(III) chloride leads to the formation of the 1:1 (Fe:Ln) 'open' complexes, whereas iron(II) trifluoromethanosulfonate allows for the synthesis of 1:2 (M:Ln) 'closed' systems. The structural differences between the individual complexes are a result of the information encoded within the metallic centre and the chosen counterion, whereas the organic scaffold influences the observed properties. Indeed, the number and nature of the external hydrogen bond donors coming from the presence of (benz)imidazole moieties in the ligand framework are responsible for the observed biological behaviour in terms of mimicking phenoxazinone synthase activity and interaction with DNA.


Assuntos
Benzimidazóis/química , Materiais Biomiméticos/química , DNA/metabolismo , Ferro/química , Oxirredutases/metabolismo , Bases de Schiff/química , Aminofenóis/metabolismo , Animais , Ligação Competitiva , Catálise , Bovinos , Fluorescência , Imidazóis , Cinética , Ligantes , Oxazinas , Oxirredução , Bases de Schiff/síntese química , Elementos de Transição/metabolismo
17.
Inorg Chem ; 58(19): 12618-12627, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31490063

RESUMO

The aim of this paper is to design near-infrared (NIR) Al3+ fluorescent probes based on a Schiff base to extend their applications in biological systems. By combining benzo[h]quinoline unit and salicylaldehyde acylhydrazone, we designed two new Schiff base derivatives. According to theoretical simulations on previous experimental Al3+ probes, we obtained the appropriate theoretical approaches to describe the properties of these fluorescent probes. By employing such approaches on our newly designed molecules, it is found that the new molecules have high selectivity toward Al3+ and that their corresponding Al3+ complexes can emit NIR fluorescence. As a result, they are expected to be potential NIR Al3+ fluorescent probes.


Assuntos
Aldeídos/química , Alumínio/análise , Corantes Fluorescentes/química , Hidrazonas/química , Cátions/análise , Modelos Moleculares , Bases de Schiff/química , Espectrometria de Fluorescência
18.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470598

RESUMO

A strategy is devised to synthesize zwitterionic acetylated cellulose nanofibrils (CNF). The strategy included acetylation, periodate oxidation, Schiff base reaction, borohydride reduction, and a quaternary ammonium reaction. Acetylation was performed in glacial acetic acid with a short reaction time of 90 min, yielding, on average, mono-acetylated CNF with hydroxyl groups available for further modification. The products from each step were characterized by FTIR spectroscopy, ζ-potential, SEM-EDS, AFM, and titration to track and verify the structural changes along the sequential modification route.


Assuntos
Celulose/síntese química , Técnicas de Química Sintética , Nanofibras/química , Ácido Acético/química , Acetilação , Boroidretos/química , Celulose/análogos & derivados , Humanos , Nanofibras/ultraestrutura , Oxirredução , Compostos de Amônio Quaternário/química , Bases de Schiff/química
19.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487951

RESUMO

To obtain highly selective toxic derivatives of fipronil, a series of Schiff bases with an alkynyl group (3a-3k) were designed and synthesized from 4-ethynylbenzaldehyde (2) and 4-substituted 5-amino-N-arylpyrazole (1a-1k) via a nucleophilic addition elimination reaction in ionic liquids. Utilization of ionic liquids was demonstrated to endow the yield of each compound beyond 50%, which was enhanced over 1.5 times of the synthetic productive rates comparing the conventional method by which longer reactive time was consumed. The derivatives were characterized via nuclear magnetic resonance hydrogen spectroscopy (1H-NMR), carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), and electrospray ionization high resolution mass spectrometry (ESI-HRMS). The cytotoxicity of these derivatives on Trichoplusia ni (Hi-5) cell and Spodoptera litura cell (SL cell) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) bioassays. The results indicated that several compounds had potential cytotoxicity on Hi-5 cell, especially a 4-ethyl substituted alkynyl Schiff base derivative (3f) that was demonstrated to possess high selective toxicity to the Hi-5 cell than the SL cell. In addition, 3f exhibited comparable toxic activity to commercial fipronil on a Hi-5 cell while a little toxic effect on the SL cell, which satisfied the expectation for selective toxicity screening.


Assuntos
Líquidos Iônicos/química , Pirazóis/síntese química , Pirazóis/farmacologia , Bases de Schiff/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Estrutura Molecular , Bases de Schiff/síntese química
20.
J Enzyme Inhib Med Chem ; 34(1): 1697-1710, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31537132

RESUMO

Inhibition of Carbonic Anhydrases (CAs) has been clinically exploited for many decades for a variety of therapeutic applications. Within a research project aimed at developing novel classes of CA inhibitors (CAIs) with a proper selectivity for certain isoforms, a series of derivatives featuring the 2-substituted-benzimidazole-6-sulfonamide scaffold, conceived as frozen analogs of Schiff bases and secondary amines previously reported in the literature as CAIs, were investigated. Enzyme inhibition assays on physiologically relevant human CA I, II, IX and XII isoforms revealed a number of potent CAIs, showing promising selectivity profiles towards the transmembrane tumor-associated CA IX and XII enzymes. Computational studies were attained to clarify the structural determinants behind the activities and selectivity profiles of the novel inhibitors.


Assuntos
Benzimidazóis/química , Inibidores da Anidrase Carbônica/síntese química , Sulfonamidas/síntese química , Aminas/química , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/química , Humanos , Isoenzimas/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas do Tecido Nervoso/antagonistas & inibidores , Bases de Schiff/química , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia
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