RESUMO
Mets7 is a methionine-rich motif present in hCtr-1 transporter that is involved in copper cellular trafficking. Its ability to bind Cu(I) was recently exploited to develop metallopeptide catalysts for Henry condensation. Here, the catalytic activity of Mets7-Cu(I) complex in Michael addition reactions has been evaluated. Furthermore, His7 peptide, in which Met residues have been substituted with His ones, was also prepared. This substitution allowed His7 to coordinate Cu (II), with the obtainment of a stable turn conformation as evicted by CD experiments. His7-Cu (II) proved also to be a better catalyst than Mets7-Cu(I) in the addition reaction. In particular, when the substrate was the (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one, a conversion of 71% and a significative 58% of e.e. was observed.
Assuntos
Cobre/química , Histidina/química , Oligopeptídeos/química , Propano/síntese química , Sítios de Ligação , Catálise , Humanos , Estrutura Molecular , Propano/análogos & derivados , Propano/químicaRESUMO
Six N-nitroaryl-2-amino-1,3-dichloropropane derivatives have been prepared and evaluated against 18 cancer cell lines and two non-cancerous cell lines. Analysis of cell viability data and IC50 values indicated that the presence of a trifluoromethyl group in the nitroaryl moiety is an important structural feature associated with the compounds' cytotoxicities.
Assuntos
Antineoplásicos/síntese química , Propano/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Metilação , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Propano/síntese química , Propano/química , Propano/farmacologia , Relação Estrutura-AtividadeRESUMO
Traditional ionic liquids (ILs) catalysts suffer from the difficulty of product purification and can only be used in homogeneous catalytic systems. In this work, by reacting ILs with co-catalyst (ZnBr2), we successfully converted three polyether imidazole ionic liquids (PIILs), i.e., HO-[Poly-epichlorohydrin-methimidazole]Cl (HO-[PECH-MIM]Cl), HOOC-[Poly-epichlorohydrin-methimidazole]Cl (HOOC-[PECH-MIM]Cl), and H2N-[Poly-epichlorohydrin-methimidazole]Cl (H2N-[PECH-MIM]Cl), to three composite PIIL materials, which were further immobilized on ZSM-5 zeolite by chemical bonding to result in three immobilized catalysts, namely ZSM-5-HO-[PECH-MIM]Cl/[ZnBr2], ZSM-5-HOOC-[PECH-MIM]Cl/[ZnBr2], and ZSM-5-H2N-[PECH-MIM]Cl/[ZnBr2]. Their structures, thermal stabilities, and morphologies were fully characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The amount of composite PIIL immobilized on ZSM-5 was determined by elemental analysis. Catalytic performance of the immobilized catalysts was evaluated through the catalytic synthesis of propylene carbonate (PC) from CO2 and propylene oxide (PO). Influences of reaction temperature, time, and pressure on catalytic performance were investigated through the orthogonal test, and the effect of catalyst circulation was also studied. Under an optimal reaction condition (130 °C, 2.5 MPa, 0.75 h), the composite catalyst, ZSM-5-HOOC- [PECH-MIM]Cl/[ZnBr2], exhibited the best catalytic activity with a conversion rate of 98.3% and selectivity of 97.4%. Significantly, the immobilized catalyst could still maintain high heterogeneous catalytic activity even after being reused for eight cycles.
Assuntos
Imidazóis/química , Líquidos Iônicos/química , Propano/análogos & derivados , Zeolitas/química , Alcenos/química , Apatitas/química , Dióxido de Carbono/química , Catálise , Imidazóis/síntese química , Líquidos Iônicos/síntese química , Microscopia Eletrônica de Varredura , Propano/síntese química , Propano/química , Difração de Raios XRESUMO
[M(sac)2(dppp)] (1 and 2), [M(dppp)2](sac)2 (3 and 4) and [M(sac)2(dppb)] (5 and 6) complexes, where Mâ¯=â¯PdII (1, 3 and 5) and PtII (2, 4 and 6), sacâ¯=â¯saccharinate, dpppâ¯=â¯1,3-bis(diphenylphosphino)propane and dppbâ¯=â¯1,4-bis(diphenylphosphino)butane, were synthesized and characterized by IR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes against human lung (A549), breast (MCF-7), prostate (DU145) and colon (HCT116) cancer cell lines showed that the cationic complexes of dppp (3 and 4) and neutral Pt complex of dppb (6) were the most active agents of series. 3 and 4 exhibited antiproliferative activity, while 6 was highly cytotoxic compared to cisplatin. These complexes were therefore subjected to further investigations to ascertain the possible role of lipophilicity, cellular uptake and DNA/HSA binding in their biological activity. Flow cytometry analysis revealed that complex 6 induced apoptotic cell death in A549 and HCT116â¯cells and caused the cell cycle arrest at the S phase and overproduction of reactive oxygen species (ROS), giving rise to mitochondrial depolarization and DNA damage.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Paládio/química , Paládio/farmacologia , Células A549 , Antineoplásicos/síntese química , Butanos/síntese química , Butanos/química , Butanos/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Células HCT116 , Humanos , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/síntese química , Fosfinas/síntese química , Fosfinas/química , Fosfinas/farmacologia , Propano/síntese química , Propano/química , Propano/farmacologiaRESUMO
We aimed to develop new effective catalysts for the synthesis of propylene carbonate from propylene oxide and carbon dioxide. A kind of Mx+LClx coordination complex was fabricated based on the chelating tridentate ligand 2,6-bis[1-(phenylimino)ethyl] pyridine (L). The obtained products were characterized by elemental analysis, infrared spectroscopy, ultraviolet spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. It was found that the catalytic activity of the complexes with different metal ions, the same ligand differed and co-catalyst, where the order of greatest to least catalytic activity was 2 > 3 > 1. The catalytic system composed of complex 2 and DMAP proved to have the better catalytic performance. The yields for complex 2 systems was 86.7% under the reaction conditions of 100 °C, 2.5 MPa, and 4 h. The TOF was 1026 h-¹ under the reaction conditions of 200 °C, 2.5 MPa, and 1 h. We also explored the influence of time, pressure, temperature, and reaction substrate concentration on the catalytic reactions. A hypothetical catalytic reaction mechanism is proposed based on density functional theory (DFT) calculations and the catalytic reaction results.
Assuntos
Dióxido de Carbono/química , Complexos de Coordenação/química , Compostos de Epóxi/química , Propano/análogos & derivados , Piridinas/química , Catálise , Cristalografia por Raios X , Reação de Cicloadição , Ligantes , Conformação Molecular , Propano/síntese química , Propano/química , Eletricidade EstáticaRESUMO
Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level(IC50 = 40 nM).
Assuntos
Inflamação/tratamento farmacológico , Inibidores de Metaloproteinases de Matriz/química , Tiazolidinas/química , Humanos , Inflamação/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/síntese química , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Propano/síntese química , Propano/química , Tiazolidinas/síntese químicaRESUMO
The multitude of biologically active compounds requires the availability of a broad spectrum of radiolabeled synthons for the development of positron emission tomography (PET) tracers. The aim of this study was to synthesize 1-iodo-2-[11 C]methylpropane and 2-methyl-1-[11 C]propanol and investigate the use of these reagents in further radiosynthesis reactions. 2-Methyl-1-[11 C]propanol was obtained with an average radiochemical yield of 46 ± 6% d.c. and used with fluorobenzene as starting material. High conversion rates of 85 ± 4% d.c. could be observed with HPLC, but large precursor amounts (32 mg, 333 µmol) were needed. 1-Iodo-2-[11 C]methylpropane was synthesized with a radiochemical yield of 25 ± 7% d.c. and with a radiochemical purity of 78 ± 7% d.c. The labelling agent 1-iodo-2-[11 C]methylpropane was coupled to thiophenol, phenol and phenylmagnesium bromide. Average radiochemical conversions of 83% d.c. for thiophenol, 40% d.c. for phenol, and 60% d.c. for phenylmagnesium bromide were obtained. In addition, [11 C]2-methyl-1-propyl phenyl sulphide was isolated with a radiochemical yield of 5 ± 1% d.c. and a molar activity of 346 ± 113 GBq/µmol at the end of synthesis. Altogether, the syntheses of 1-iodo-2-[11 C]methylpropane and 2-methyl-1-[11 C]propanol were achieved and applied as proof of their applicability.
Assuntos
1-Propanol/química , 1-Propanol/síntese química , Radioisótopos do Iodo/química , Propano/química , Propano/síntese química , Alquilação , Marcação por Isótopo , Tomografia por Emissão de Pósitrons , RadioquímicaRESUMO
Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in LPS-activated mouse peritoneal macrophages. Among the tested compounds, a 1,3-diarylpropane analog, 2-(3-(3,4-dimethoxyphenyl)propyl)-5-methoxyphenol (3p), displayed the most significant inhibitory effects against NO production. To investigate the mechanism of action, the effects of 3p on iNOS and COX-2 protein expression were studied by immunoblot. The results concluded that 3p is capable of inhibiting iNOS expression in LPS-induced RAW264.7 cells via attenuation of NF-κB signaling by ERK, p38, and JNK.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Chalconas/farmacologia , Fenóis/farmacologia , Propano/análogos & derivados , Propano/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Linhagem Celular , Chalconas/síntese química , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/síntese química , Fosforilação , Propano/síntese química , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
A library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC50 value of 0.29 µM. Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT).
Assuntos
Doença de Chagas/tratamento farmacológico , Chalconas/química , Propano/análogos & derivados , Piridinas/síntese química , Piridinas/farmacologia , Tripanossomicidas/síntese química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Doença de Chagas/parasitologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Propano/síntese química , Propano/farmacologia , Relação Estrutura-AtividadeRESUMO
An efficient synthesis of dihydrostilbenes (1-5) and diarylpropanes (6-10) is achieved from the commercially available starting materials and Wittig-Horner reaction, Claisen-Schmidt condensation and hydrogenation as key steps. Later, their nitric oxide (NO) production inhibition effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity. All the tested compounds significantly decreased NO production in a concentration-dependent manner except compounds 2, 6 and 8 and did not show notable cytotoxicity except compound 1. Two compounds i.e., compound 9 (hindsiipropane B) (100%; IC50=1.84µM) possessed the most potent NO inhibitory activity which was even stronger than the positive control, L-NMMA (90.1%; IC50=2.73µM) followed by compound 4 (75.5%; IC50=2.98µM) at 10µM concentration and this finding was also further correlated by suppressed expression of LPS stimulated inducible NO synthase. Our study revealed that compound 9, a 1,3-diarylpropane scaffold with 3â³,4â³-dimethoxyphenyl and 3',4'-dihydroxy-2'-methoxyphenyl motifs could be considered as potential compound or lead compound for further development of NO production-targeted anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Óxido Nítrico/antagonistas & inibidores , Propano/química , Propano/farmacologia , Estilbenos/química , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/síntese química , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Propano/síntese química , Células RAW 264.7 , Estilbenos/síntese químicaRESUMO
A series of Mannich bases having piperidine moiety were reacted with 2-mercaptoethanol, leading to 1-aryl-3-piperidine-4-yl-1-propanone hydrochlorides. The cytotoxicity and carbonic anhydrase inhibitory activities of these new compounds were evaluated. Among the compounds, only one derivative, nitro substituent bearing EU9, showed an effective cytotoxicity, although weak tumor specificity against human oral malignant versus nonmalignant cells. The compound induced apoptosis in HSC-2 oral squamous cell carcinoma cells, but not in human gingival fibroblast. Chemical modifications of this lead are thus necessary to further investigate it as a drug candidate and to obtain compounds with a better activity profile.
Assuntos
Antineoplásicos/farmacologia , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Propano/farmacologia , Compostos de Sulfidrila/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Propano/síntese química , Propano/química , Relação Estrutura-Atividade , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/químicaRESUMO
In this work we report the discovery of new homo and hetero bis-piperazinyl-1-propanone derivatives as selective ligands for 5-HT7 over 5-HT1A receptor. These newly synthesized compounds possess a 4-arylpiperazine linked through an acyl spacer to another substituted piperazine system and were tested for their binding properties on human cloned 5-HT1A and 5-HT7 serotonin receptors. Among these, phenyl, 4- and 2-chlorophenyl, 2-methoxyphenyl, 2-pyridyl, and 2-pyrimidyl derivatives 15, 24, 25, and 27-29 displayed nanomolar affinity values for the 5-HT7 receptor (Ki 23.5-52.0nM) and no affinity for the 5-HT1A receptor.
Assuntos
Desenho de Fármacos , Piperazinas/química , Propano/análogos & derivados , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/síntese química , Humanos , Cinética , Ligantes , Piperazina , Propano/síntese química , Propano/metabolismo , Ligação Proteica , Receptores de Serotonina/química , Antagonistas da Serotonina/química , Antagonistas da Serotonina/metabolismo , Relação Estrutura-AtividadeRESUMO
Indazole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent dual inhibitors of cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH). In continuation of our structure-activity studies on cPLA2α and FAAH inhibitors, a number of derivatives of these substances characterized by bioisosteric replacement of the carboxylic acid functionality by inverse amides, sulfonylamides, carbamates and ureas were prepared. The biological evaluation of the obtained compounds showed that the carboxylic acid functionality of the lead compounds is of special importance for a pronounced inhibition of cPLA2α and FAAH.
Assuntos
Amidoidrolases/antagonistas & inibidores , Ácidos Carboxílicos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Indazóis/farmacologia , Propano/análogos & derivados , Amidoidrolases/metabolismo , Animais , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Fosfolipases A2 do Grupo IV/metabolismo , Indazóis/síntese química , Indazóis/química , Estrutura Molecular , Propano/síntese química , Propano/química , Propano/farmacologia , Relação Estrutura-Atividade , SuínosRESUMO
An efficient asymmetric synthesis of 11-ß-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.
Assuntos
11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Naftóis/síntese química , Propano/análogos & derivados , 11-beta-Hidroxiesteroide Desidrogenases/química , Catálise , Cetonas/química , Naftóis/química , Propano/síntese química , Propano/química , EstereoisomerismoRESUMO
Cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are serine hydrolases. cPLA2α is involved in the generation of pro-inflammatory lipid mediators, FAAH terminates the anti-inflammatory effects of endocannabinoids. Therefore, inhibitors of these enzymes may represent new drug candidates for the treatment of inflammation. We have reported that certain 1-heteroarylpropan-2-ones are potent inhibitors of cPLA2α and FAAH. The serine reactive ketone group of these compounds, which is crucial for enzyme inhibition, is readily metabolized resulting in inactive alcohol derivatives. In order to obtain metabolically more stable inhibitors, we replaced this moiety by α-ketoheterocyle, cyanamide and nitrile serine traps. Investigations on activity and metabolic stability of these substances revealed that in all cases an increased metabolic stability was accompanied by a loss of inhibitory potency against cPLA2α and FAAH, respectively.
Assuntos
Amidoidrolases/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Cetonas/farmacologia , Propano/farmacologia , Serina/farmacologia , Amidoidrolases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Fosfolipases A2 do Grupo IV/metabolismo , Humanos , Cetonas/química , Estrutura Molecular , Propano/síntese química , Propano/química , Serina/química , Relação Estrutura-AtividadeRESUMO
A series of hydroxy substituted amino chalcone compounds have been synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cell lines. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two novel amino chalcone compounds exhibited higher tyrosinase inhibitory activities (IC50 values of 9.75µM and 7.82µM respectively) than the control kojic acid (IC50: 22.83µM). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 4.82µM and 1.89µM respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirm that the active inhibitors strongly interact with mushroom tyrosinase residues. This study suggests that the depigmenting effect of novel amino chalcone compounds might be attributable to inhibition of tyrosinase activity, suggesting amino chalcones to be a promising candidate for use as depigmentation agents or as anti-browning food additives.
Assuntos
Chalconas/síntese química , Chalconas/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fenóis/síntese química , Fenóis/farmacologia , Propano/análogos & derivados , Animais , Linhagem Celular Tumoral , Melaninas/antagonistas & inibidores , Camundongos , Propano/síntese química , Propano/farmacologia , Preparações Clareadoras de Pele/farmacologiaRESUMO
Four compounds are reported, all of which lie along a versatile reaction pathway which leads from simple carbonyl compounds to terphenyls. (2E)-1-(2,4-Dichlorophenyl)-3- [4-(prop-1-en-2-yl)phenyl]prop-2-en-1-one, C18H14Cl2O, (I), prepared from 4-(prop-1-en-2-yl)benzaldehyde and 2,4-dichloroacetophenone, exhibits disorder over two sets of atomic sites having occupancies of 0.664â (6) and 0.336â (6). The related chalcone (2E)-3-(4-chlorophenyl)-1-(4-fluorophenyl)prop-2-en-1-one reacts with acetone to produce (5RS)-3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]cyclohex-2-en-1-one, C21H21ClO, (II), which exhibits enantiomeric disorder with occupancies at the reference site of 0.662â (4) and 0.338â (4) for the (5R) and (5S) forms; the same chalcone reacts with methyl 3-oxobutanoate to give methyl (1RS,6SR)-4-(4-chlorophenyl)-6-[4-(propan-2-yl)phenyl]-2-oxocyclohex-3-ene-1-carboxylate, C23H23ClO3, (III), where the reference site contains both (1R,6S) and (1S,6R) forms with occupancies of 0.923â (3) and 0.077â (3), respectively. Oxidation, using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, of ethyl (1RS,6SR)-6-(4-bromophenyl)-4-(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate, prepared in a similar manner to (II) and (III), produces ethyl 4''-bromo-4-fluoro-5'-hydroxy-1,1':3',1''-terphenyl-4'-carboxylate, C21H16BrFO3, (IV), which crystallizes with Z' = 2 in the space group P-1. There are no significant intermolecular interactions in the structures of compounds (I) and (II), but for the major disorder component of compound (III), the molecules are linked into sheets by a combination of C-H...O and C-H...π(arene) hydrogen bonds. The two independent molecules of compound (IV) form two different centrosymmetric dimers, one built from inversion-related pairs of C-H...O hydrogen bonds and the other from inversion-related pairs of C-H...π(arene) hydrogen bonds. Comparisons are made with related compounds.
Assuntos
Benzaldeídos/química , Chalcona/análogos & derivados , Chalcona/química , Cicloexanonas/química , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/síntese química , Propano/análogos & derivados , Chalcona/síntese química , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura Molecular , Propano/síntese química , Propano/química , EstereoisomerismoRESUMO
A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of their (1)H NMR, (13)C NMR, Mass spectroscopic datas and elemental analysis. The results demonstrate that these compounds are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent compound (2E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl] prop-2-en-1-one showed the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.22±0.01µM and 0.05 comparable to that standard drug, Selegiline Ki and SI values were found as 0.33±0.03µM and 0.04, respectively. Molecular docking studies were carried out to further explain the in vitro results of the new compounds, and to identify the hypothetical binding mode for the compounds inside the inhibitor binding cavity of hMAO-B.
Assuntos
Chalconas/síntese química , Chalconas/farmacologia , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/farmacologia , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/efeitos dos fármacos , Propano/análogos & derivados , Humanos , Propano/síntese química , Propano/farmacologiaRESUMO
P,C-stereogenic 1,3-bisphosphinylpropanes 3 that have up to five stereogenic centers could be obtained stereoselectively in high yields by a one-step reaction of (RP)-menthylphenylphosphine oxide 1 with α,ß-unsaturated aldehydes 2 catalyzed by KOH at room temperature. A mechanism was proposed as to involve a stereoselective intermolecular 1,3'-phosphorus migration from the 1,2-adduct of 1 with 2 to another 2 generating a 1,4-adduct that subsequently reacts with 1 to produce 3.
Assuntos
Ácidos Fosfínicos/síntese química , Propano/síntese química , Aldeídos/química , Catálise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Ácidos Fosfínicos/química , Propano/análogos & derivados , Propano/química , EstereoisomerismoRESUMO
Misfolded protein amyloid-beta protein (Aß) and tau protein are two high hallmarks of Alzheimer's disease (AD), representing significant targets in treating AD. Researches on mechanisms of the two proteins inducing neuron dysfunctions provide therapeutic strategies of AD, including inhibition of Aß production and aggregation, acceleration of Aß clearance as well as reduction of tau hyperphosphorylation. Proteoglycans (PGs) consist of a core protein and glycosaminoglycans (GAGs) chains, with enormous structural diversity due to variation in the core protein, the number of GAGs chains as well as extent and position of sulfation. Considerable evidences have indicated that PGs and GAGs play important roles in Aß and tau processing. Numbers of GAGs and analogues have potential therapeutic function in AD. In this Review, we focus on the relationship of PGs and GAGs with misfolded proteins in AD and their potential therapeutic implications.