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1.
J Agric Food Chem ; 67(38): 10660-10666, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31479263

RESUMO

Two new indolyl diketopiperazines, gartryprostatins A and B (1 and 2), with an unusual 2,3-furan-fused pyrano[2,3-g]pyrrolo[1″,2″:4',5']pyrazino[1',2':1,5]pyrrolo[2,3-b]indole nucleus, along with a new naturally occurring compound (gartryprostatin C, 3) were isolated from the solid culture of Aspergillus sp. GZWMJZ-258, an endophyte from Garcinia multiflora (Guttiferae). The structures of compounds 1-3 were determined by nuclear magnetic resonance, mass spectrometry, Marfey's analysis of amino acids, and chemical calculation. Compounds 1-3 displayed selective inhibition on human FLT3-ITD mutant AML cell line, MV4-11, with IC50 values of 7.2, 10.0, and 0.22 µM, respectively.


Assuntos
Aspergillus/química , Dicetopiperazinas/farmacologia , Endófitos/química , Garcinia/microbiologia , Plantas Medicinais/microbiologia , Aspergillus/genética , Aspergillus/isolamento & purificação , Aspergillus/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicetopiperazinas/química , Dicetopiperazinas/metabolismo , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular
2.
Acta Crystallogr C Struct Chem ; 75(Pt 9): 1250-1258, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484813

RESUMO

A drug-drug anhydrous pharmaceutical salt containing tolbutamide {systematic name: 3-butyl-1-[(4-methylbenzene)sulfonyl]urea, TOL, C12H18N2O3S} and metformin (systematic name: 1-carbamimidamido-N,N-dimethylmethanimidamide, MET, C4H11N5) was created based on antidiabetic drug combinations to overcome the poor pharmaceutical properties of the parent drugs. Proton transfer and the proportion of the two components were confirmed by 1H NMR spectroscopy and single-crystal X-ray diffraction analysis. Comprehensive characterization of the new pharmaceutical salt crystal, 2-[(dimethylamino)(iminiumyl)methyl]guanidine (butylcarbamoyl)[(4-methylbenzene)sulfonyl]azanide, C4H12N5+·C12H17N2O3S-, was performed and showed enhancement of the pharmaceutical properties, such as lower hygroscopicity and greater accelerated stability than the parent drug MET, and higher solubility and dissolution rate than TOL. The property alterations were correlated with the crystal packing features and potential hydrogen-bonding sites through observed changes in the crystal structures.


Assuntos
Hipoglicemiantes/farmacologia , Metformina/farmacologia , Tolbutamida/farmacologia , Cristalografia por Raios X , Combinação de Medicamentos , Ligações de Hidrogênio , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Metformina/síntese química , Metformina/química , Estrutura Molecular , Solubilidade , Tolbutamida/síntese química , Tolbutamida/química
3.
J Agric Food Chem ; 67(38): 10764-10773, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31487158

RESUMO

It has been hypothesized that the α-methylene-γ-lactone moiety of sesquiterpene lactones is a key unit for their bioactivity. As a consequence, modifications of these compounds have been focused on this fragment. In the work reported here, two sesquiterpene lactones, namely, dehydrocostuslactone and ß-cyclocostunolide, a eudesmanolide obtained by controlled cyclization of costunolide, were chosen for modification by Michael addition at C-13. On applying this reaction to both compounds, it was possible to introduce the functional groups alkoxy, amino, carbamoyl, hydroxy, and thiol to give products in good to high yields, depending on the base and solvent employed. In particular, the introduction of a thiol group at C-13 in both compounds was achieved with outstanding yields (>90%) and this is unprecedented for these sesquiterpene lactones. The bioactivities of the products were evaluated on etiolated wheat coleoptile elongation and germination of seeds of parasitic weeds, with significant activity observed on Orobanche cumana and Phelipanche ramosa. The structure-activity relationships are discussed.


Assuntos
Lactonas/química , Orobanchaceae/química , Orobanche/química , Extratos Vegetais/química , Plantas Daninhas/química , Sesquiterpenos/química , Germinação , Estrutura Molecular , Orobanchaceae/crescimento & desenvolvimento , Orobanche/crescimento & desenvolvimento , Plantas Daninhas/crescimento & desenvolvimento , Sementes/química , Sementes/crescimento & desenvolvimento , Compostos de Sulfidrila/química
4.
J Agric Food Chem ; 67(38): 10744-10755, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31525900

RESUMO

We previously reported that ß-glucosidase BGL1 at low concentration (15 µg mL-1) from Coprinopsis cinerea exhibited hydrolytic activity only toward laminarioligosaccharides but not toward cellooligosaccharides and gentiobiose. This study shows that BGL1 at high concentration (200 µg mL-1) also hydrolyzed cellobiose and gentiobiose, which accounted for only 0.83 and 2.05% of its activity toward laminaribiose, respectively. Interestingly, BGL1 at low concentration (1.5 µg mL-1) showed transglycosylation but BGL1 at high concentration (200 µg mL-1) did not. BGL1 utilizes only laminarioligosaccharides but not glucose, gentiobiose, and cellobiose to synthesize the higher oligosaccharides. BGL1 transferred one glucosyl residue from substrate laminarioligosaccharide to another laminarioligosaccharide as an acceptor in a ß(1 → 3) or ß(1 → 6) fashion to produce higher laminarioligosaccharides or 3-O-ß-d-gentiobiosyl-d-laminarioligosaccharides. The BGL1-digested laminaritriose exhibited approximately 90% enhancement in the anti-oxidant activity compared to that of untreated laminaritriose, implying a potential application of BGL1-based transglycosylation for the production of high value-added rare oligosaccharides.


Assuntos
Agaricales/enzimologia , Dissacarídeos/metabolismo , Proteínas Fúngicas/química , Oligossacarídeos/metabolismo , beta-Glucosidase/química , Agaricales/química , Agaricales/genética , Sequência de Aminoácidos , Dissacarídeos/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glicosilação , Hidrólise , Cinética , Estrutura Molecular , Oligossacarídeos/química , Especificidade por Substrato , beta-Glucosidase/genética , beta-Glucosidase/metabolismo
5.
Top Curr Chem (Cham) ; 377(5): 26, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529210

RESUMO

Lignin, one of the main components of lignocellulosic biomass, is the largest renewable source of aromatics on the planet and presents an extraordinary opportunity for being used in the production of bio-based products. It can be transformed for the substitution of aromatic chemical-derived petrol as BTXs. The wide range of applications that it can be obtained from BTXs building blocks makes the selective depolymerization of lignin a great scientific challenge. This review emphasizes the different strategies for the fragmentation of lignin to monomers or aromatics hydrocarbons. Thus, a by-product traditionally discarded or used for energy generation, it could be valorized into high added-value products.


Assuntos
Benzeno/química , Lignina/química , Tolueno/química , Xilenos/química , Líquidos Iônicos/química , Estrutura Molecular , Polimerização
6.
Top Curr Chem (Cham) ; 377(5): 25, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529217

RESUMO

Metal-organic frameworks (MOFs) have gathered tremendous interest among researchers for their potential applications such as in storage and separation. While some progress has been made towards shaping of MOFs to realize industrial applications, the mechanical properties of MOFs remain more or less unexplored. Over the last decade, this area has witnessed a steady growth in terms of understanding the mechanical stability of MOFs and its consequence on their performance. In this review, the mechanical properties of the reported macroscopic shaped MOF structures (mainly granules, pellets, tablets, monoliths, and gels) are discussed. Conclusions are then drawn to determine which shapes and shaping techniques promise to meet industrial requirements on the basis of mechanical stability. Finally, future research directions are proposed to improve our understanding, and possibly enhance stability, by correlating the properties from microscopic single-crystalline level to the industrially relevant macroscopic polycrystalline scale.


Assuntos
Estruturas Metalorgânicas/química , Estrutura Molecular , Tamanho da Partícula , Porosidade , Propriedades de Superfície
7.
Top Curr Chem (Cham) ; 377(5): 28, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31563994

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the joints, with the main clinical manifestations being chronic, symmetrical, and peripheral multi-joint inflammatory lesions. Drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), disease-modifying anti-rheumatic drugs (DMARDs), and biologics play a very important role in the treatment of RA. Of these, the most commonly used are chemical drugs, such as NSAIDs, GCs, and DMARDs. In recent years, a number of new compounds have emerged for the treatment of RA, such as SYK inhibitors, JAK inhibitors, NSAID-CAI drugs, and Syk/PDGFR-α/c-Kit inhibitors. In this review, we summarize the most recently developed anti-RA chemical drugs and discuss the synthesis and biological activities of these various new compounds.


Assuntos
Antirreumáticos/síntese química , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Animais , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Humanos , Estrutura Molecular
8.
Phys Chem Chem Phys ; 21(37): 20628-20640, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31495862

RESUMO

Methionine synthase (MetH) is a methylcobalamin (MeCbl)-dependent mammalian enzyme which plays a critical role in carrying out the transfer of a methyl group from methyl tetrahydrofolate to homocysteine to generate methionine and tetrahydrofolate. This catalytic cycle proceeds via cleavage of a Co-C bond which is formally heterolytic. This cleavage results in a structural change in the MeCbl cofactor bound to an enzyme. Unlike the native catalysis, upon photoexcitation, the Co-C bond in MeCbl-bound MetH generates the Co(ii)/CH3 radical pairs (RPs). Protein residues of the cap domain, particularly phenylalanine708 (F708) and leucine 715 (L715), which surrounds the upper face of the MeCbl cofactor, inhibit the photolysis of MeCbl by caging the CH3 radical and inducing the geminate recombination of the Co(ii)/CH3 RP. A molecular-level understanding of these effects requires a detailed investigation of the low-lying electronic states. Toward this, we have mutated the F708 residue with alanine (A708) and constructed the potential energy surfaces (PESs) for the low-lying S1 electronic state using a combined quantum mechanics/molecular mechanics (QM/MM) approach. The S1 PESs for the wild-type (WT) and mutant enzymes are the result of crossing of two electronic states, namely metal-to-ligand charge transfer (MLCT) and ligand field (LF) states, indicated by a seam. It is shown that the topologies of the S1 PESs are significantly modulated by introducing a mutation at the F708 position. Specifically, for the WT enzyme, the energy barrier of photoreaction and the energy difference between MLCT and LF minima are markedly higher than those of its mutant counterpart. Moreover, mutation influences the photoactivation of the Co-C bond in enzyme-bound MeCbl by decreasing the rate of geminate recombination and altering the rate of radical pair formation. This theoretical insight was also compared with transient absorption spectroscopic (TAS) studies which are in good agreement with the present findings.


Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Carbono/química , Cobalto/química , Vitamina B 12/análogos & derivados , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Modelos Químicos , Estrutura Molecular , Mutação/genética , Fotólise , Domínios Proteicos/genética , Vitamina B 12/metabolismo
9.
Pestic Biochem Physiol ; 159: 41-50, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400783

RESUMO

Emerging fungal phytodiseases are a food security threat and novel fungicides are in an urgent need. Herein, a series of isobutyrophenone derivatives were designed and synthesized. The derivatives exhibited excellent fungicidal activities against seven fungi. The structure-activity relationship (SAR) study indicated that the introduction of a bromo group at the position 3 or 5 of the phenyl ring, as well as esterification of the 4-hydroxy with a chloroacetyl group, could substantially increase the antifungal activity and spectrum of the compounds. Among all 23 compounds, 2-bromo-3-hydroxy-4-isobutyryl-6-methylphenyl 2-chloroacetate (12b) showed the highest fungicidal activity against all seven tested fungal pathogens with EC50 values ranging from 1.22 to 39.94 µg/mL and exhibited the most potent inhibition against class II fructose-1,6-bisphosphate aldolase with an IC50 of 3.63 µM. The lead compounds were proven to be safe to NIH3T3/293 T cells and silkworm larvae, and relatively stable under different harsh conditions. Detached fruit tests showed the practical potential of lead compounds for fruit (or plant) protection. Taken together, our results indicated that the isobutyrophenone derivatives could be further optimized and developed as advanced leads for new fungicides.


Assuntos
Antifúngicos/química , Antifúngicos/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Animais , Bombyx/metabolismo , Linhagem Celular , Frutose-Bifosfato Aldolase/genética , Humanos , Larva/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Relação Estrutura-Atividade
10.
Chem Pharm Bull (Tokyo) ; 67(8): 733-771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366825

RESUMO

Transition-metal nanoparticles (NPs) catalysts supported on solid material represent one of the most important subjects in organic synthesis due to their reliable carbon-carbon or carbon-heteroatom bond-forming cross-coupling reactions. Therefore methodologically and conceptually novel immobilization methods for nonprecious transition-metal NPs are currently required for the development of organic, inorganic, green, materials, and medicinal chemistry. We discovered a self-assembled Au-supported Pd NPs catalyst (SAPd(0)) and applied it as a catalyst to Suzuki-Miyaura coupling, Buchwald-Hartwig reaction, Carbon(sp2 and sp3)-Hydrogen bond functionalization, double carbonylation, removal of the allyl protecting groups of allyl esters, and redox switching. SAPd(0) comprises approximately 10 layers of self-assembled Pd(0) NPs, whose size is less than 5 nm on the surface of a sulfur-modified Au. The Pd NPs are wrapped in a sulfated p-xylene polymer matrix. We thought that the self-assembled Au-supported Pd NPs could be made by in situ metal NP and nanospace simultaneous organization (PSSO). This methodology involves 4 kinds of simultaneous procedures: i) reduction of a higher valence metal salt, ii) growth of metal NPs with appropriate size, iii) growth of a matrix with appropriate pores, and iv) wrapping of the metal NPs by matrix nanopores. This methodology is different from previously reported metal NPs-immobilizing methods, which use solid supports with preformed pores or coordination sites. We also applied the in situ PSSO method to prepare various immobilized transition-metal NPs, including base metals. For example, the in situ PSSO method can be applicable to easily prepare Ni, Ru, and Fe NPs with good recyclability and low metal leaching for use in organic synthesis.


Assuntos
Descoberta de Drogas , Nanopartículas Metálicas/química , Compostos Orgânicos/síntese química , Elementos de Transição/química , Catálise , Estrutura Molecular , Compostos Orgânicos/química
11.
Chem Pharm Bull (Tokyo) ; 67(8): 775-777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366826

RESUMO

Nocardia is a potent bacterial producer of bioactive compounds. From a culture of Nocardia beijingensis NBRC 16342, we isolated four aromatic compounds, named beijinchromes A-D (1-4). We purified them by silica gel chromatography and reverse phase HPLC, and identified their structures by NMR and high resolution (HR)-MS analyses. 1, 2, and 4 are novel 1,2,3,8-tetrasubstituted naphthalenes, and 3 is a novel 3,8-disubstituted ortho-naphthoquinone. 1 and 2 exert antioxidant activities, and 3 exhibits antibiotic activity. Remarkably, the putative biosynthetic gene clusters for 1-4 are widely distributed in 37 Nocardia species, implying their potential to produce this family of compounds and important biological functions of beijinchromes.


Assuntos
Hidrocarbonetos Aromáticos/isolamento & purificação , Nocardia/química , Composição de Medicamentos , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Estereoisomerismo
12.
Chem Pharm Bull (Tokyo) ; 67(8): 786-794, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366828

RESUMO

Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying anti-rheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The results of anti-inflammatory effect showed that compared with the control group, the external TEF microemulsion group could significantly inhibit swelling of paw in rats, and no significant difference compared with oral LEF group. The results of hepatotoxicity test show that there were normal content of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and no obvious inflammatory infiltration of TEF microemulsion group compared with LEF group. The plasma concentration curve showed that compared with LEF group, the peak concentration of TEF microemulsion group was decreased, the half-life (t1/2) was prolonged, and the relative bioavailability of TEF microemulsion was 75.35%. These results suggest that TEF W/O microemulsion can be used as a promising preparation to play an anti-inflammatory role while significantly reducing hepatotoxicity.


Assuntos
Antirreumáticos/farmacologia , Crotonatos/farmacologia , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Toluidinas/farmacologia , Animais , Antirreumáticos/química , Crotonatos/química , Composição de Medicamentos , Edema/patologia , Emulsões/síntese química , Emulsões/química , Estrutura Molecular , Óleos/química , Medição da Dor , Ratos , Ratos Sprague-Dawley , Toluidinas/química , Água/química
13.
Chem Pharm Bull (Tokyo) ; 67(8): 810-815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366830

RESUMO

Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.


Assuntos
Antibacterianos/farmacologia , Citocromo P-450 CYP2C19/metabolismo , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Omeprazol/farmacologia , Amoxicilina/química , Amoxicilina/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Claritromicina/química , Claritromicina/farmacologia , Citocromo P-450 CYP2C19/química , Combinação de Medicamentos , Humanos , Metronidazol/química , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Omeprazol/antagonistas & inibidores , Omeprazol/metabolismo , Tinidazol/química , Tinidazol/farmacologia
14.
Chem Pharm Bull (Tokyo) ; 67(8): 816-823, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366831

RESUMO

In this present study a new co-crystals of zoledronic acid with DL-tartaric acid and nicotinamide has been developed with improved solubility. Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology. Pharmaceutical cocrystals are multi-component crystals with a stoichiometric ratio of active pharmaceutical ingredients (APIs) and cocrystal coformers (CCFs) that are assembled by noncovalent interactions such as hydrogen bonds, π-π packing, and Vander Waals forces. In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1 : 2 and 2 : 1 increased by fold as compared to pure drug.


Assuntos
Desenho de Drogas , Niacinamida/química , Tartaratos/química , Ácido Zoledrônico/química , Varredura Diferencial de Calorimetria , Cristalização , Estrutura Molecular , Difração de Pó , Solubilidade , Ácido Zoledrônico/síntese química
15.
Chem Pharm Bull (Tokyo) ; 67(8): 824-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366832

RESUMO

We synthesized and evaluated novel 5-[2-(thiophen-2-yl)propan-2-yl]-4H-1,2,4-triazole derivatives as 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors. Optimization of the thiophene ring and the substituents on the 1,2,4-triazole ring produced 3,4-dicyclopropyl-5-{2-[3-fluoro-5-(trifluoromethyl)thiophen-2-yl]propan-2-yl}-4H-1,2,4-triazole monohydrochloride (9a), which showed potent and selective inhibitory activity against human 11ß-HSD1. Compound 9a was also metabolically stable against human and mouse liver microsomes. Oral administration of 9a to diabetic ob/ob mice lowered corticosterone levels in adipose tissue, and thereby reduced plasma glucose and insulin levels in a dose-dependent manner.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Administração Oral , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Células HEK293 , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Obesos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/química
16.
Chem Pharm Bull (Tokyo) ; 67(8): 872-876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366835

RESUMO

A gold-catalyzed introduction of various terminal alkynes to acetals was investigated. Extensive optimization of the reaction conditions revealed that thermally stable cationic gold catalysts bearing bulky ligands such as 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene 3-1H-benzo[d][1,2,3]triazolyl gold trifluoromethanesulfonate (IPrAu(BTZ-H)OTf) were particularly suitable for the reaction. Additionally, significant solvent effects were observed. Ether solvents such as tetrahydrofuran (THF), cyclo pentyl methyl ether (CPME), and 1,4-dioxane were effective for the reaction. Studies on the scope of substrates and alkynes indicated that various alkynes and acetals were feasible to provide a wide range of propargylic ethers.


Assuntos
Acetais/química , Alquinos/química , Éteres/síntese química , Ouro/química , Alquinos/síntese química , Éteres/química , Estrutura Molecular
17.
Chem Pharm Bull (Tokyo) ; 67(8): 877-883, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366836

RESUMO

The 4-vinylpyrimidin-2-one nucleoside (T-vinyl) forms a cross-link with the RNA containing uracil at the complementary site at a high reaction rate. To obtain the stable T-vinyl derivative so that its reactivity is protected until it access to the target site, several derivatives were investigated, and the 2-thiopyridinyl- and 2-thiopyrimidinyl T-vinyl derivatives were determined to be good candidates. The 2-thiopyrimidinyl T-vinyl derivative was found to more efficiently cross-link with mRNA albeit having a better stability than the 2-thiopyridinyl T-vinyl derivative. The investigation using the luciferase (Luc) mRNA, the synthetic mRNA and non-cellular translation system revealed that the translation is terminated at the end of the cross-linked duplex between the mRNA and the oligoribonucleotide (ORN). Thus, the 2-thiopyrimidinyl T-vinyl derivative has successfully demonstrated both a good stability and high efficiency for the cross-linking reaction, and expanded its applicability in biological applications.


Assuntos
Reagentes para Ligações Cruzadas/química , Nucleosídeos/química , Oligorribonucleotídeos/química , RNA Mensageiro/química , Compostos de Vinila/química , Reagentes para Ligações Cruzadas/síntese química , Estrutura Molecular , Nucleosídeos/síntese química , Compostos de Vinila/síntese química
18.
Chem Pharm Bull (Tokyo) ; 67(8): 888-895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366838

RESUMO

New sugar hydrazones incorporating furan and/or 1,3,4-thiadiazole ring systems were synthesized by reaction of the corresponding hydrazide with different aldose sugars. Heterocyclization of the formed hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the heterocyclization process. The anticancer activity of the synthesized compounds was studied against human liver carcinoma cell (HepG-2) and at human normal retina pigmented epithelium cells (RPE-1). High activities were revealed by compounds 3, 12 and 14 with IC50 values near to that of the reference drug doxorubicin.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Furanos/farmacologia , Oxidiazóis/farmacologia , Açúcares/farmacologia , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/síntese química , Furanos/química , Células Hep G2 , Humanos , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade , Açúcares/síntese química , Açúcares/química , Tiadiazóis/síntese química , Tiadiazóis/química
19.
Science ; 365(6456): 866-867, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31467210
20.
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
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