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1.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1091-1101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380792

RESUMO

A new set of differently hydrated barium and strontium squarates, namely poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium] monohydrate], {[Ba(C4O4)(H2O)3]·H2O}n (1), poly[[diaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)strontium] monohydrate], {[Sr(C4O4)(H2O)2]·H2O}n (2), and poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium/strontium(0.85/0.15)] monohydrate], {[Ba0.85Sr0.15(C4O4)(H2O)3]·H2O}n (3), is reported. The study of their crystal structures indicates that all the complexes crystallize in the triclinic space group P-1. Complexes 1 and 3 have a rare combination of squarate units coordinated through monodentate O atoms to two different metal atoms and through two bidentate O atoms to three different metal atoms. Furthermore, they have three coordinated water molecules to give a coordination number of nine. The squarate ligands in complex 2 exhibit two different coordination modes: (i) monodentate O atoms coordinated to four different Sr atoms and (ii) two monodentate O atoms coordinated to two different metal atoms with the other two O atoms bidentate to four different Sr atoms. All the compounds decompose to give the respective carbonates when heated to 800 °C, as evidenced by thermogravimetry/differential thermal analysis (TG-DTA), which are clusters of nanoparticles. Complexes 1 and 3 show additional endothermic peaks at 811 and 820 °C, respectively, indicating the phase transition of BaCO3 from an orthorhombic (α-Pmcn) to a trigonal phase (ß-R3m). All three complexes have significant DNA-binding constants, ranging from 2.45 × 104 to 9.41 × 104 M-1 against EB-CT (ethidium bromide-calf thymus) DNA and protein binding constants ranging from 1.1 × 105 to 8.6 × 105 with bovine serum albumin. The in vitro cytotoxicity of the complexes is indicated by the IC50 values, which range from 128.8 to 261.3 µg ml-1. Complex 3 shows better BSA binding, antioxidant activity against the DPPH radical and cytotoxicity than complexes 1 and 2.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclobutanos/farmacologia , Depuradores de Radicais Livres/farmacologia , Substâncias Intercalantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Bário/química , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/metabolismo , DNA/metabolismo , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Humanos , Ligações de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Células MCF-7 , Estrutura Molecular , Ligação Proteica , Soroalbumina Bovina/metabolismo , Estrôncio/química , Água/química
2.
J Agric Food Chem ; 67(26): 7281-7288, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31198027

RESUMO

Potential metabolites of bioactive compounds are important for their biological activities and as authentic standards for metabolic studies. The phenolic compounds contained in olive oil are an important part of the human diet, and therefore their potential metabolites are of utmost interest. We developed a convenient, scalable, one-pot chemoenzymatic method using the arylsulfotransferase from Desulfitobacterium hafniense for the sulfation of the natural olive oil phenols tyrosol, hydroxytyrosol, and of their monoacetylated derivatives. Respective monosulfated (tentative) metabolites were fully structurally characterized using LC-MS, NMR, and HRMS. In addition, Folin-Ciocalteu reduction, 1,1-diphenyl-2-picrylhydrazyl radical scavenging, and antilipoperoxidant activity in rat liver microsomes damaged by tert-butylhydroperoxide were measured and compared to the parent compounds. As expected, the sulfation diminished the radical scavenging properties of the prepared compounds. These compounds will serve as authentic standards of phase II metabolites.


Assuntos
Arilsulfotransferase/química , Proteínas de Bactérias/química , Depuradores de Radicais Livres/química , Álcool Feniletílico/análogos & derivados , Acetilação , Biocatálise , Cromatografia Líquida de Alta Pressão , Desulfitobacterium/enzimologia , Depuradores de Radicais Livres/síntese química , Espectrometria de Massas , Estrutura Molecular , Azeite de Oliva/química , Fenóis/química , Álcool Feniletílico/síntese química , Álcool Feniletílico/química , Sulfatos/química
3.
Eur J Med Chem ; 177: 414-424, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158754

RESUMO

Due to the role of butyrylcholinesterase (BChE) in acetylcholine hydrolysis in the late stages of the Alzheimer's disease (AD), inhibitors of butyrylcholinesterase (BChE) have been recently envisaged, besides acetylcholinesterase (AChE) inhibitors, as candidates for treating mild-to-moderate AD. Herein, synthesis and AChE/BChE inhibition activity of some twenty derivatives of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (HHAI) is reported. Most of the newly synthesized HHAI derivatives achieved the inhibition of both ChE isoforms with IC50s in the micromolar range, with a structure-dependent selectivity toward BChE. Apparently, molecular volume and lipophilicity do increase selectivity toward BChE, and indeed the N2-(4-phenylbutyl) HHAI derivative 15d, which behaves as a mixed-type inhibitor, resulted the most potent (IC50 0.17 µM) and selective (>100-fold) inhibitor toward either horse serum and human BChE. Moreover, 15d inhibited in vitro self-induced aggregation of neurotoxic amyloid-ß (Aß) peptide and displayed neuroprotective effects in neuroblastoma SH-SY5Y cell line, significantly recovering (P < 0.001) cell viability when impaired by Aß1-42 and hydrogen peroxide insults. Overall, this study highlighted HHAI as useful and versatile scaffold for developing new small molecules targeting some enzymes and biochemical pathways involved in the pathogenesis of AD.


Assuntos
Azepinas/farmacologia , Inibidores da Colinesterase/farmacologia , Indóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Peptídeos beta-Amiloides/metabolismo , Azepinas/síntese química , Azepinas/química , Azepinas/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Domínio Catalítico , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Relação Dose-Resposta a Droga , Desenho de Drogas , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Humanos , Indóis/síntese química , Indóis/química , Indóis/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Relação Estrutura-Atividade
4.
Eur J Med Chem ; 174: 216-225, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31042617

RESUMO

The identification of a valid therapeutic treatment for Alzheimer's disease (AD) represents nowadays an urgent and still unmet medical need, since currently available anti-AD drugs only relieve symptoms and show a modest efficacy. Recent evidence indicates that multi-target-directed ligands (MTDLs) can potentially provide an effective strategy to develop innovative therapies directed towards the onset and progression of this multifactorial neurodegenerative disorder. In this work we designed, synthesized and evaluated a new series of MTDLs bearing the rivastigmine skeleton (ChE-inhibitor) linked to known metal-chelating moieties with linkers of different length. For all the novel derivatives, AChE/BuChE inhibitory activity, ROS scavenging activity and potential cytotoxicity have been assessed. For the best compound (4), copper chelating properties and neuroprotective effects were also evaluated. Our data demonstrated that hybrid derivative 4 is able to effectively inhibit AChE and BuChE and to chelate copper, showing a protective action on neurons. These results, although preliminary, indicate that compound 4 can be considered as a possible hit molecule for the development of new anti-AD MTDLs.


Assuntos
Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Fármacos Neuroprotetores/farmacologia , Rivastigmina/análogos & derivados , Rivastigmina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/metabolismo , Linhagem Celular Transformada , Quelantes/síntese química , Quelantes/toxicidade , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Camundongos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/toxicidade , Rivastigmina/síntese química , Rivastigmina/toxicidade
5.
Comput Biol Chem ; 80: 54-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901601

RESUMO

Development of novel, safe and effective drug candidates combating the emerging drug resistance has remained a major focus in the mainstream of anti-tuberculosis research. Here, we inspired to design and synthesize series of new pyridin-4-yl-1,3,4-oxadiazol-2-yl-thio-ethylidene-hydrazinecarbothioamide derivatives as potential anti-tubercular agents. The anti-tubercular bioactive assay demonstrated that the synthesized compounds exhibit potent anti-tubercular activity (MIC = 3.9-7.81 µg/mL) in comparison with reference drugs Rifampicin and Isoniazid.We employed pharmacophore probing approach for the identification of CYP51 as a possible drug target for the synthesized compounds. To understand the preferable binding mode, the synthesized molecules were docked onto the active site of Sterol 14 α-demethylases (CYP51) target. From the binding free energy of the docking results it was revealed that the compounds were effective CYP51 inhibitors and acts as antitubercular agent.


Assuntos
Antituberculosos/farmacologia , Oxidiazóis/farmacologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/metabolismo , Domínio Catalítico , Família 51 do Citocromo P450/química , Família 51 do Citocromo P450/metabolismo , Desenho de Drogas , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Oxidiazóis/síntese química , Oxidiazóis/química , Oxidiazóis/metabolismo , Ligação Proteica , Piridinas/síntese química , Piridinas/química , Piridinas/metabolismo , Rifampina/farmacologia , Relação Estrutura-Atividade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/metabolismo
6.
J Biochem Mol Toxicol ; 33(5): e22291, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719827

RESUMO

Widespread use of cerium oxide (CeO2 ) nanoparticles (NPs) is found in almost all areas of research due to their distinctive properties. CeO2 NPs synthesized via green chemistry have been characterized for antioxidant, phytochemical, and biological potential. Physical characterization through scanning electron microscopy, XRD, and TGA showed that the NPs are circular in shape, 20-25 nm in size, and stable in a wide range of temperature. NPs display significant antioxidant (32.7% free radical scavenging activity) and antileishmanial (IC50 48 µg mL-1 ) properties. In vitro toxicity tested against lymphocytes verified that NPs are biocompatible (99.38% viability of lymphocytes at 2.5 µg mL-1 ). In vivo toxicity experiments showed no harmful effects on rat serum chemistry and histology of various organs and did not even change the concentration of antioxidative enzymes, total protein contents, lipid peroxidation, and nitrosative stress. These observations are in line with the statement that plant-based synthesis of CeO2 NPs lessens or nullifies in vitro and in vivo toxicity and hence CeO2 NPs are regarded as a safe and biocompatible material to be used in drug delivery.


Assuntos
Cério , Depuradores de Radicais Livres , Teste de Materiais , Nanopartículas/química , Extratos Vegetais/química , Rhus/química , Animais , Cério/química , Cério/farmacologia , Feminino , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Humanos , Ratos , Ratos Sprague-Dawley
7.
Arch Pharm (Weinheim) ; 352(2): e1800221, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30600538

RESUMO

An improved methodology is reported for the synthesis of new series of mesotetrakis[aryl]-21H,23H-porphyrin derivatives 2a-h and was considered as a model to study their antioxidant and cytotoxic activities. The structures of the novel compounds were determined in 1 H and 13 C NMR, UV-Vis, and elemental analyses. Among the derivatives, compounds 2c, 2d, and 2h showed strongest radical-scavenging activity. Moreover, according to our results, compounds 2c, 2d, 2g, and 2h have very strong activity against the HepG2 hepatoma cell line, with IC50 values from 9 to 25 µg/mL. Molecular docking was performed to investigate the binding between the most active porphyrin derivatives 2c, 2d, 2g, 2h and the two molecular targets Bcl-2 and caspase-3. Compounds 2c and 2d seem to have better affinities to both proteins than 2g and 2h.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Porfirinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Células Hep G2 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Porfirinas/síntese química , Porfirinas/química , Relação Estrutura-Atividade
8.
Int J Biol Macromol ; 128: 391-400, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30684583

RESUMO

Lignin, is the most abundant, renewable and degradable biopolymer available in the nature. The present study exploited purified lignin from wheat straw as reducing, capping and stabilizing agent for the green synthesis of silver nanoparticles (Li-AgNPs) under optimized conditions. The analytical studies revealed synthesized Li-AgNPs having a face centered cubic crystalline structure, size ranging ~15-20 nm and the biomolecules comprising majorly phenolic, hydroxyl and carboxylic group of lignin coated on the surface of AgNPs. Li-AgNPs showed significant antimicrobial efficacy against human pathogens namely; Staphylococcus aureus and Escherichia coli and also determined their minimum inhibitory and minimum bactericidal concentration (MIC and MBC). Li-AgNPs also displayed substantial antioxidant activity in terms of well-known enzyme marker viz.; ABTS and DPPH free radical scavenging assay relative to commercial AgNPs. In vitro cytotoxicity assay of Li-AgNPs demonstrated dose-dependent toxicity effects in SKOV3 ovarian cancer cell line (LD50; 150 µg/mL) indicative of promising anticancer agent. Further, H2O2 sensing ability of stabilized Li-AgNPs exhibited its vital role in determining reactive oxygen species. Synthesis of Li-AgNPs is a cheap green technology and could exhibit its commercial use in biomedical, cosmetic, and pharmaceutical industry.


Assuntos
Peróxido de Hidrogênio/análise , Lignina/química , Nanopartículas Metálicas , Prata/química , Prata/farmacologia , Triticum/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Benzotiazóis/química , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Escherichia coli/efeitos dos fármacos , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Química Verde , Humanos , Picratos/química , Prata/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Ácidos Sulfônicos/química
9.
Bioorg Med Chem ; 27(2): 410-415, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30554969

RESUMO

The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH radical with IC50 values ranging from 5.08 to 19.20 µg mL-1, and some of them also reduced ABTS+ radical and TPTZ-Fe3+ complex in ABTS+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity.


Assuntos
Depuradores de Radicais Livres/química , Compostos Organometálicos/química , Telúrio/química , Animais , Benzotiazóis/química , Compostos de Bifenilo/química , Desenho de Drogas , Fibroblastos/efeitos dos fármacos , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/toxicidade , Camundongos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/toxicidade , Oxirredução , Picratos/química , Relação Estrutura-Atividade , Ácidos Sulfônicos/química
10.
Carbohydr Polym ; 206: 468-475, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553346

RESUMO

Free radicals are closely related to the occurrence and development of aging, cancer and inflammation. In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to graft the collagen peptide (COP) molecules on the amino group of carboxymethyl chitosan sulfate (CMCS) to improve the antioxidant effects. FT-IR and NMR spectroscopy were used to confirm the successful grafting of COP to CMCS. Degree of substitution (DS) of CMCS-COP could be controlled by adjusting the reaction conditions. With the increase of concentration, the ability of each sample on scavenging capacity and reducibility tends to increase obviously. The results of anticoagulant experiments showed that the ability of CMCS and CMCS-COP with three different degrees of substitution on activated partial thrombin time (APTT) and prothrombin time (PT) values were all increased to compare with the control group. No relevant cytotoxicity against NIH-3T3 mouse fibroblasts was found for the copolymers. These results suggested that CMCS-COP would appear to be a promising candidate for wound dressing application.


Assuntos
Quitosana/análogos & derivados , Colágeno/farmacologia , Fragmentos de Peptídeos/farmacologia , Transglutaminases/química , Animais , Anticoagulantes/síntese química , Anticoagulantes/química , Anticoagulantes/farmacologia , Anticoagulantes/toxicidade , Bandagens , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Quitosana/toxicidade , Colágeno/síntese química , Colágeno/química , Colágeno/toxicidade , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Camundongos , Estrutura Molecular , Células NIH 3T3 , Oxirredução , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Tempo de Protrombina , Temperatura Ambiente
11.
Carbohydr Polym ; 206: 493-503, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30553350

RESUMO

In this paper, a series of 6-O-imidazole-based quaternary ammonium chitosan derivatives via 6-O-chloroacetyl chitosan (CAClC) were successfully designed and synthesized. Detailed structural characterization was carried out by means of FT-IR and 1H NMR spectroscopy, and elemental analysis. Furthermore, the antioxidant property against hydroxyl radicals, superoxide radicals, and DPPH radicals was evaluated in vitro. 2-(N,N,N-trimethyl)-6-O-(2-aminobenzimidazole)acetyl chitosan chloride (2NPhMC) and 2-(N,N,N-trimethyl)-6-O-(1-butylimidazole)acetyl chitosan chloride (NBMC) showed more than 90% scavenging indices at 1.6 mg/mL. Besides, the antifungal activity against Botrytis cinerea and Gibberella zeae was estimated using in vitro MIC and hypha measurements. Most of the quaternized chitosan derivatives especially with the long length alkyl chain and primary amino group showed an inhibitory index of > 85% at 1.0 mg/mL against Botrytis cinerea. Besides, the cytotoxicity of chitosan and all the quaternized chitosan derivatives was evaluated in vitro on HaCaT cells and all the quaternized chitosan derivatives bearing 6-O-imidazole exhibited low cytotoxicity. These results suggested that chitosan derivatives bearing 6-O-imidazole-based quaternary ammonium salts may be used as good biomaterials.


Assuntos
Antifúngicos/farmacologia , Quitosana/análogos & derivados , Quitosana/farmacologia , Depuradores de Radicais Livres/farmacologia , Imidazóis/farmacologia , Compostos de Amônio Quaternário/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/toxicidade , Botrytis/efeitos dos fármacos , Quitosana/síntese química , Quitosana/toxicidade , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/toxicidade , Gibberella/efeitos dos fármacos , Células HeLa , Humanos , Imidazóis/síntese química , Imidazóis/química , Imidazóis/toxicidade , Testes de Sensibilidade Microbiana , Micélio/efeitos dos fármacos , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/toxicidade , Solubilidade
12.
Eur J Med Chem ; 157: 14-27, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30071406

RESUMO

Twenty-seven novel benzo[c][1,2,5]selenadiazole-5-carboxylic acid (BSCA) derivatives were designed and synthesized. Anti-proliferative activity of these structures was tested in vitro against a panel of five human cancer cell lines, including prostate (PC-3), colon (HT-29), leukemia (CCRF-CEM), lung (HTB-54) and breast (MCF-7). Four compounds (5, 6, 7 and 19) showed potent inhibitory activity with GI50 values below 10 µM in at least one of the cancer cell lines. The selectivity of these compounds was further examined in two non-malignant cell lines derived from breast (184B5) and lung (BEAS-2B). Compound 7 exhibited promising anti-proliferative activity (GI50 = 3.7 µM) in MCF-7 cells, together with high selectivity index (SI > 27.1). The induction of cell death by compound 7 was independent of the apoptotic process and it did not affect cell cycle progression either. Likewise, radical scavenging properties of the new selenadiazole derivatives were confirmed by testing their ability to scavenge DPPH radicals. Four compounds (1, 2, 8 and 9) showed potent radical scavenging activity, compound 9 being the most effective. Overall, while compound 7 was identified as the most cell growth inhibitory agent and selectively toxic to cancer cells, compound 9 proved to be the most potent antioxidant among the selenadiazole derivatives synthesized. This series of compounds can serve as an excellent scaffold to achieve new and potent antioxidant compounds useful for several diseases, i.e. cancer, neurodegenerative, heart diseases and leishmaniasis, considering the high radical scavenging activity and low toxicity showed by most of the compounds.


Assuntos
Antineoplásicos/farmacologia , Depuradores de Radicais Livres/farmacologia , Compostos Organosselênicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/antagonistas & inibidores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Picratos/antagonistas & inibidores , Relação Estrutura-Atividade
13.
Free Radic Res ; 52(6): 685-697, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29642746

RESUMO

Biologically and chemically useful hydrazinoimidazolines were evaluated as antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH•), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging assays, ferric ions reducing power assay, and ex vivo model of rat erythrocytes exposed to 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH) or H2O2 were used. The most potent DPPH• scavengers proved to be hydrazinoimidazolines 3, 2, and 4, revealing excellent antiradical effects - superior or comparable to that of all antioxidant standards used. Moreover, these molecules showed strong NO neutralising potencies - better to that of ascorbic acid (AA) (3), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (3 and 2), butylated hydroxytoluene (BHT) (3 and 2), and butylated hydroxyanisole (BHA) (3, 2, and 4). Compound 4 was also effective in GOR scavenging. The excellent scavenger of GOR, NO, and H2O2 proved to be structure 5, with the potency superior or comparable to the majority of antioxidant standards used. In turn, compound 9 was effective in H2O2 and GOR neutralisation. All hydrazinoimidazolines revealed the reducing power that is higher than BHT. Moreover, the protective effects of most test compounds on oxidatively stressed erythrocytes were observed. Some structure-activity relationships were disclosed. A significance of the primary hydrazino group on antioxidant effects was confirmed. The most likely DPPH• and GOR scavenging mechanisms for test compounds were propound. Among all the investigated molecules, hydrazinoimidazolines 5, 3, 2, 4, and 9, due to their excellent or good antiradical activities, can represent promising antioxidant candidates with prospective utility for prevention of diseases related to reactive oxygen/nitrogen species.


Assuntos
Compostos Benzidrílicos/antagonistas & inibidores , Depuradores de Radicais Livres/farmacologia , Hidrazinas/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Imidazolinas/farmacologia , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Animais , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Compostos Benzidrílicos/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Hidroxianisol Butilado/química , Hidroxianisol Butilado/farmacologia , Hidroxitolueno Butilado/química , Hidroxitolueno Butilado/farmacologia , Cromanos/química , Cromanos/farmacologia , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Depuradores de Radicais Livres/síntese química , Hidrazinas/síntese química , Peróxido de Hidrogênio/farmacologia , Imidazolinas/síntese química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/química , Picratos/antagonistas & inibidores , Picratos/química , Ratos , Relação Estrutura-Atividade
14.
J Fluoresc ; 28(2): 655-662, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29680927

RESUMO

Furopyridine III, namely 1-(3-amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one, synthesized from 4-(4-(tert-butyl)phenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile I in two steps. The title compound is characterized by NMR, MS and its X-ray structure. The molecular structure consists of planar furopyridine ring with both phenyl rings being inclined from the furopyridine scaffold to a significant different extent. There are three intramolecular hydrogen bonds within the structure. The lattice is stabilized by N-H…O, H2C-H …π and π…π intermolecular interactions leading to three-dimensional network. Compound III exhibits fluorescent properties, which are investigated. Antimicrobial potential and antioxidant activity screening studies for the title compound III and the heterocyclic derivatives, I and II, show no activity towards neither bacterial nor fungal strains, while they exhibited weak to moderate antioxidant activity compared to reference.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Piridinas/síntese química , Piridinas/farmacologia , Anti-Infecciosos/química , Compostos de Bifenilo/química , Técnicas de Química Sintética , Cristalografia por Raios X , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Ligações de Hidrogênio , Modelos Moleculares , Conformação Molecular , Picratos/química , Piridinas/química , Espectrometria de Fluorescência
15.
Carbohydr Polym ; 190: 175-183, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29628235

RESUMO

Chondroitin sulfate (CS) was regio-specifically modified to an unsaturated derivative (ΔCS) with a double bond in positions 4 and 5 of N-acetyl-d-galactosamine. The structure of ΔCS was elucidated in detail by two dimensional nuclear magnetic resonance, ultraviolet spectroscopy and mass spectrometry. The introduction of a nucleophilic CC double bond into a polymer backbone had no influence on biocompatibility of CS, which was demonstrated by MTT live-dead assay and enzymatic degradation in vitro. On the other hand the chemical modification significantly enhanced the reactivity of ΔCS towards numerous oxidizing agents, which might be promising for a variety of biomedical and cosmetic applications.


Assuntos
Sulfatos de Condroitina/química , Sulfatos de Condroitina/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/síntese química , Células 3T3 , Animais , Compostos de Bifenilo/química , Técnicas de Química Sintética , Sulfatos de Condroitina/toxicidade , Depuradores de Radicais Livres/toxicidade , Teste de Materiais , Camundongos , Oxirredução , Picratos/química
16.
Int J Biol Macromol ; 114: 751-758, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29588203

RESUMO

Varisized chitosan-selenium (CS-Se) nanocomposites were synthesized through an innovative method. It is the first time to use CS both as reductant and stabilizer to synthesize selenium nanoparticles (SeNPs). By manipulating the temperature, the well-dispersed CS-Se nanocomposites were synthesized via a simple one pot reaction with the size ranging from 83 to 208nm before being characterized by TEM, DLS, UV-vis, FTIR, XRD and TG analyses. The results showed that SeO32- was reduced to a stable SeNPs colloid at a comparatively high temperature, the amino group and hydroxyl group of CS were conjugated to the surface of SeNPs. Besides, the antioxidant activities of CS-Se nanocomposites were investigated by DPPH, ABTS+, hydroxyl radical, metal ion chelating and reducing power assays, which proved to be concentration-dependent, size-dependent and exhibited good antioxidant activities. The results suggested that CS-Se nanocomposites might be considered as a more appropriate selenium-adding form to achieve antioxidative goals in food.


Assuntos
Antioxidantes/síntese química , Quitosana/química , Nanocompostos , Selênio/química , Antioxidantes/química , Benzotiazóis , Coloides , Relação Dose-Resposta a Droga , Depuradores de Radicais Livres/síntese química , Radical Hidroxila , Quelantes de Ferro/síntese química , Nanocompostos/química , Oxirredução , Tamanho da Partícula , Ácidos Sulfônicos , Temperatura Ambiente
17.
Molecules ; 23(3)2018 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-29495379

RESUMO

Chitosan (CS) is an abundant and renewable polysaccharide that is reported to exhibit a great variety of beneficial properties. However, the poor solubility of chitosan in water limits its applications. In this paper, we successfully synthesized single N-quaternized (QCS) and double N-diquaternized (DQCS) chitosan derivatives, and the resulting quaternized materials were water-soluble. The degree of quaternization (DQ) of QCS and DQCS was 0.8 and 1.3, respectively. These derivatives were characterized by FTIR, ¹H NMR, 13C NMR, TGA, and SEM. Moreover, the antioxidant activity of the chitosan was evaluated by free radical scavenging ability (against DPPH-radical, hydroxyl-radical, and superoxide-radical) and ferric reducing power. Our results suggested that the antioxidant abilities were in the order of DQCS > QCS > CS, which was consistent with the number of quaternized groups. These data demonstrate that the number of quaternized groups of chitosan derivatives contributes to their antioxidant activity. Therefore, DQCS, with a higher number of quaternized groups and higher positive charge density, is endowed with high antioxidant activity, and can be used as a candidate material in food and pharmaceutical industries.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Quitosana/química , Quitosana/farmacologia , Antioxidantes/síntese química , Técnicas de Química Sintética , Quitosana/síntese química , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
18.
Eur J Pharm Sci ; 114: 285-292, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29292017

RESUMO

Dissolving microneedle (DMN) is an attractive, minimally invasive transdermal drug delivery technology. The drugs encapsulated in the DMNs are exposed to a series of thermal, chemical, and physical stresses during the fabrication process, decreasing their therapeutic activity. Current DMN fabrication methods, such as micro-molding, drawing lithography, droplet-born air blowing, and centrifugal lithography, undergo different manufacturing processes involving differing stress conditions. Among the methods, we compared the effects of two droplet-based methods, droplet-born air blowing and centrifugal lithography, on the activity of encapsulated drugs using epidermal growth factor and ascorbic acid as model drugs. Although the appearance and physical properties of DMNs fabricated by the two methods were similar, the immunoreactivity of encapsulated epidermal growth factor in centrifugal lithography and droplet-born air blowing was 92.08±2.86% and 80.67±8.00%, respectively, at baseline, and decreased to 75.32±19.40% and 41.75±16.17%, respectively, 24h after drug-loading. The free-radical scavenging activity of ascorbic acid was maintained at 88.24±0.78% in DMNs fabricated by centrifugal lithography, but decreased over time to 67.02±1.11% in DMNs fabricated by droplet-born air blowing. These findings indicate that the manufacturing conditions of centrifugal lithography exert less stress on the drug-loaded DMNs, minimizing activity loss over time, and therefore that centrifugal lithography is suitable for fabricating DMNs loaded with fragile biological drugs.


Assuntos
Ácido Ascórbico/síntese química , Portadores de Fármacos/síntese química , Fator de Crescimento Epidérmico/síntese química , Microinjeções/métodos , Agulhas , Animais , Ácido Ascórbico/administração & dosagem , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Fator de Crescimento Epidérmico/administração & dosagem , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/síntese química , Camundongos , Células NIH 3T3 , Solubilidade
19.
Med Chem ; 14(4): 372-386, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29205120

RESUMO

BACKGROUND: A new series of 13 piperazinyl flavone derivatives has been synthesized and examined for their in vitro antiradical and antioxidant activities in response to the pharmacy industry's increasing demand for new non-toxic anti-inflammatory and anticancer drugs. METHOD: Their antioxidant activity was evaluated by the reactive oxygen species (ROS) scavenging assays, 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH•) and 2,2'-azino-bis(3- ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS+•) scavenging assays, and the ferric reducing antioxidant potency (TAC) method, and was compared to known positive controls, herbal infusions, and penicillins. Chemiluminescence, spectrophotometry, electron spin resonance (ESR) and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques. RESULT: It was seen that synthesized compounds have a wide spectrum of antioxidant property. Some of the test compounds proved to be extremely efficient scavengers of H2O2 exhibiting, in some cases, EC50 of about 2 µM. The values of antioxidant status (TAS) were in the range of 49 ± 3.9 to 1283 ± 51.3 µM TE/g (TE = Trolox equivalent) and were lower than that of butylated hydroxytoluene (BHT) (1304 ± 43.2 µM TE/g) and green tea (1356 ± 40.0 µM TE/g), but for several synthesized compounds, they were higher than chamomille infusion and penicillins. Ferric reducing antioxidant powers (TAC) for the piperazinyl flavone derivatives were in the range 7 ± 0.5 to 104 ± 0.6 µM TE/g and were weaker than that of BHT (217 ± 5.3 µM TR/g ). CONCLUSION: Carboxylic or hydroxamic acid substituted piperazinyl flavones are potentially active as antioxidants, thus may be suggested as pharmacologically interesting ones.


Assuntos
Flavonas/farmacologia , Depuradores de Radicais Livres/farmacologia , Piperazinas/farmacologia , Ácido Ascórbico/farmacologia , Hidroxitolueno Butilado/farmacologia , Camellia sinensis , Dicloxacilina/farmacologia , Flavonas/síntese química , Flavonas/química , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Matricaria , Penicilina G/farmacologia , Piperazinas/síntese química , Piperazinas/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Chás de Ervas
20.
J Biochem Mol Toxicol ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29243863

RESUMO

In this study, three substituted polyhalogenated nitrobutadiene derivatives were synthesized. Compound 1-[(2,3-dibromopropyl)sulfanyl]-1,3,4,4-tetrachloro-2-nitrobuta-1,3-diene (4) was synthesized before by our group. Compounds 8-{[1-[(2,3-dibromopropyl)sulfany]-3,4,4-trichloro-2-nitrobuta-1,3-butadien-1-yl}-1,4-dioxa-8-azaspiro[4.5]decane (5) and 1-[(2,3-dibromopropyl)sulfanyl]-3,4,4-trichloro-N-(4-methylpiperazin-1-yl)-2-nitrobuta-1,3-diene-1-amine (6) were synthesized in this work as original compounds. Xanthine oxidase, elastase inhibition abilities, and antioxidant activities were investigated in this work for compounds 4, 5, and 6. In this study, compounds 4, 5, and 6 exhibited antixanthine oxidase, antielastase, and antioxidant activities. Among the compounds screened, compound 4 exhibited xanthine oxidase and elastase inhibitor effect similar to the standard compound. Among the three tested compounds, compound 6 showed potent DPPH radical scavenging and reducing power activities. Therefore, these three compounds (4, 5, and 6) may be useful as an antixanthine oxidase, antielastase, and antioxidant agent in pharmaceutical and cosmetic industry.


Assuntos
Antioxidantes/farmacologia , Butadienos/farmacologia , Inibidores Enzimáticos/farmacologia , Hidrocarbonetos Halogenados/farmacologia , Elastase de Leucócito/antagonistas & inibidores , Inibidores de Serino Proteinase/farmacologia , Xantina Oxidase/antagonistas & inibidores , Antioxidantes/síntese química , Antioxidantes/química , Butadienos/síntese química , Butadienos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Supressores da Gota/síntese química , Supressores da Gota/química , Supressores da Gota/farmacologia , Humanos , Hidrocarbonetos Halogenados/síntese química , Hidrocarbonetos Halogenados/química , Cinética , Elastase de Leucócito/metabolismo , Estrutura Molecular , Nootrópicos/síntese química , Nootrópicos/química , Nootrópicos/farmacologia , Inibidores de Serino Proteinase/síntese química , Inibidores de Serino Proteinase/química , Temperatura de Transição , Xantina Oxidase/metabolismo
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