Modification of polyetheretherketone (PEEK) physical features to improve osteointegration / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polyetheretherketone (PEEK) has been widely applied in orthopedics because of its excellent mechanical properties, radiolucency, and biocompatibility. However, the bioinertness and poor osteointegration of PEEK have greatly limited its further application. Growing evidence proves that physical factors of implants, including their architecture, surface morphology, stiffness, and mechanical stimulation, matter as much as the composition of their surface chemistry. This review focuses on the multiple strategies for the physical modification of PEEK implants through adjusting their architecture, surface morphology, and stiffness. Many research findings show that transforming the architecture and incorporating reinforcing fillers into PEEK can affect both its mechanical strength and cellular responses. Modified PEEK surfaces at the macro scale and micro/nano scale have positive effects on cell-substrate interactions. More investigations are necessary to reach consensus on the optimal design of PEEK implants and to explore the efficiency of various functional implant surfaces. Soft-tissue integration has been ignored, though evidence shows that physical modifications also improve the adhesion of soft tissue. In the future, ideal PEEK implants should have a desirable topological structure with better surface hydrophilicity and optimum surface chemistry.

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

Asymmetric bioreduction of ketoesters derivatives by Kluyveromyces marxianus: influence of molecular structure on the conversion and enantiomeric excess

ABSTRACT This study presents the bioreduction of six β-ketoesters by whole cells of Kluyveromyces marxianus and molecular investigation of a series of 13 β-ketoesters by hologram quantitative structure-activity relationship (HQSAR) in order to relate with conversion and enantiomeric excess of β-stereogenic-hydroxyesters obtained by the same methodology. Four of these were obtained as (R)-configuration and two (S)-configuration, among them four compounds exhibited >99% enantiomeric excess. The β-ketoesters series LUMO maps showed that the β-carbon of the ketoester scaffold are exposed to undergo nucleophilic attack, suggesting a more favorable β-carbon side to enzymatic reduction based on adopted molecular conformation at the reaction moment. The HQSAR method was performed on the β-ketoesters derivatives separating them into those provided predominantly (R)- or (S)-β-hydroxyesters. The HQSAR models for both (R)- and (S)-configuration showed high predictive capacity. The HQSAR contribution maps suggest the importance of β-ketoesters scaffold as well as the substituents attached therein to asymmetric reduction, showing a possible influence of the ester group carbonyl position on the molecular conformation in the enzyme catalytic site, exposing a β-carbon side to the bioconversion to (S)- and (R)-enantiomers.

Lipoxygenase inhibitory tetraketones: potential Remedial source for inflammation and asthma / Las tetracetonas inhibidoras de la lipoxigenasa: fuente potencial Remedial para la inflamación y el asma

OBJETIVE: A series of tetraketones has been synthesized by way of a one pot synthesis and screened for inhibitory activity against the enzyme lipoxygenase. METHOD: An efficient and high yielding one pot synthesis to tetraketones [2-22] has been developed by way of tetraethyl ammonium bromide (Et4N+Br-) mediated condensation of cyclohexane-1, 3-dione [1] with a variety of aldehydes. Lipoxygenase enzyme solution was prepared so that enzyme concentration in reaction mixture was adjusted to give rates of 0.05 absorbance/minute. The test compounds were prepared in methanol of concentrations 50, 25, 12.5, 6.25 and 3.125 µM. The reaction mixture contained 160 µL (100 mM) sodium phosphate buffer (pH 8.0), 10µL of test-compound solution and 20µL of lipoxygenase solution. The contents were mixed and incubated for 10 minutes at 25ºC. The reaction was then initiated by the addition of 10µL substrate solution (linoleic acid, 0.5 mM, 0.12% w/v tween 20 in the ratio of 1:2), with the formation of (9Z,11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate, the change of absorbance at 234 nm was followed for 6 minutes. The concentrations of the test compounds that inhibited the lipoxygenase activity by 50% (IC50) were determined by monitoring the effect of increasing concentrations of these compounds in the assays on the degree of inhibition. The IC50 values were calculated by means of the EZ-Fit Enzyme-Kinetics Program (Perrella Scientific Inc., Amherst, USA). RESULT: The tetraketones [2-22] were synthesized in high yields (91-98%) using mild reaction conditions. Most of these compounds showed significant inhibitory activity against the enzyme lipoxygenase. It was found that the presence of substituents which increase delocalization of electrons enhances the inhibitory activity. CONCLUSION: It is concluded that the study is likely to lead to the discovery of therapeutically efficient agents against important disorders such as inflammation and asthma.

OBJETIVO: Una serie de tetracetonas han sido sintetizadas mediante síntesis de varios pasos en un solo reactor (one-pot), y examinadas en relación con su actividad inhibitoria frente a la enzima lipoxigenasa. MÉTODO: Una síntesis one-pot de un rendimiento alto y eficiente para la obtención de tetracetonas (2-22) ha sido desarrollada mediante bromuro amónico tetraetílico (Et4N+Br-) - de ciclohexano-1,3-diona, con una variedad de aldehídos. La solución de enzima lipoxigenasa fue preparada de modo que la concentración de la enzima en las mezcla de la reacción fue ajustada para que diera tasas de 0.05 absorbancia/minuto. Los compuestos de la prueba fueron preparados en metanol de concentraciones (50, 25, 12.5, 6.25 y 3.125 µM). La mezcla de reacción contenía 160 µL (100 mM) de un tampón (buffer) de fosfato de sodio (pH 8.0), 10µL de solución de compuesto de prueba, y 20µL de solución de lipoxigenasa. Los contenidos fueron mezclados e incubados por 10 minutos a 25ºC. La reacción fue iniciada entonces por la adición de 10µL de solución substrato (ácido linoleico, 0.5 mM, 0.12% p/v tween 20 en proporción de 1:2), con la formación de (9Z, 11E)-(13S)-13-hidroperoxioctadeca-9,11-dienoato, el cambio de absorbancia a 234 nm fue seguido por 6 minutos. Las concentraciones de los compuestos de prueba que inhibían la actividad de la lipoxigenasa en un 50% (IC50) fueron determinadas monitoreando el efecto del aumento de las concentraciones de estos compuestos en los ensayos sobre el grado de inhibición. Los valores IC50 fueron calculados mediante el Programa Cinética de la Enzima EZ-Fit (Perrella Scientific Inc., Amherst, USA). RESULTADOS: Las tetracetonas (2-22) se sintetizaron con elevados rendimientos (91-98%) usando condiciones de reacción leve. La mayoría de estos compuestos mostraron una actividad inhibitoria significativa frente a la enzima lipoxigenasa. Se halló que la presencia de sustituyentes que aumentan la deslocalización de los electrones contribuye a mejorar la actividad inhibitoria. CONCLUSIÓN: Se concluye que es probable que el estudio conduzca al descubrimiento de agentes terapéuticamente eficientes frente a trastornos importantes tales como la inflamación y el asma.

Antifungal activity of conjugated styryl ketones.

The susceptibility of Aspergillus fumigatus to a series of alpha, beta-unsaturated styryl ketones known to be thiol-alkylators was examined, and the results were compared with those obtained for Candida albicans. Among 13 compounds used in our study, one (designated NC1110) inhibited the growth of A. fumigatus completely at low concentrations (minimum inhibitory concentration = 32 microM). Structure-activity analysis of these compounds indicated that the electron attracting property as well as the overall hydrophobicity of the compounds are important parameters for their antifungal activity. These preliminary results suggest that further modification of these molecules to enhance their hydrophobicity and the electron attracting property may result in more active compounds with improved antifungal activity.

Spectroscopic studies of some new azino compounds

The electronic absorption spectra of some new azino compounds derived from hydrazine and different aldehyde and ketones are investigated in organic solvents of varying polarities. The important bands in the IR spectra and the main 1H NMR signals are assigned and discussed in relation to molecular structure. Although work on the absorption spectra of azino compounds has been reported in the literature [1-3], a series of new azino compounds derived from hydrazine and different aldehyde and ketones was prepared and in order to throw more light on their structures, these compounds were subjected to elemental analysis, spectroscopic studies and Uv-visible spectral behavior in organic solvents of varied polarity. The study included also the assignment of IR bands and 1H NMR signals by considering the effect of molecular structure on the spectral behavior

Reductive debromination of erythro-2,3-dibromo-1-cyclopropyl-3- [p-substituted phenyl] -1-propanones

Reductive debromination of erythro-2,3-dibromo-1-cyclopropyl-3-[p- substituted phenyl]-1-propanones was carried out with sodium thiophenoxide in 1: 2 molar ratio in absolute ethanol. All dibromides gave the same product; namely, trans-1-cyclopropyl-3-[p- substituted phenyl]-2-propanones. The configuration of the obtained products was assigned by PMR spectra. The possible reaction mechanism was presented

Cyanoethylation and mannich reactions with 4-aroyl-6-phenylpyridazin-3 [2H] -ones

As a part of our recent studies on pyridazinyl ketones[1-3], 4-aroyl-6-phenylpyridazin -3[2H]- ones were recently prepared in this laboratory by a new general and convenient method [1]. We would like to report, in this part, some reactions of these aroyl pyridazinones. When 4- aroyl -6-phenylpyridazin-3[2H]-ones [la-c] were allowed to react with acrylonitrile in ethanol containing catalytic amounts of aqueous sodium hydroxide, they underwent a Michael- type addition to the activated double bond yielding 4-aroyl-2[2'-cyanoethyl]-6-phenylpyridazin-3[2H]-ones[2a-c], respectively

Kinetics of the reactions of methyl-2,3-dibromo-3- [4-substituted phenyl] propanoates with piperidine IV

The rates of elimination of a series of erythromethyl- 2,3-dibromo-3-[4-substituted phenyl] propanoates [1 alpha-d] have been determined conductimetrically in methanol using piperidine as a base. The elimination reactions gave exclusively Z-methyl-2-bromo-3- [4-substituted phenyl] propanoates [2 alpha-d]. The specific rate constants of the reactions gave a good Hammett correlation with p values of 0.39-1.31 which suggest a carbonionic transition state. The results suggested that the reaction proceeds by initial isomerization of the erythro-dibromo-compound to the threo-isomer, which spontaneously eliminates HBr to give [2 alpha-d]

Nucleophilic ring opening of some epoxy ketones

The reaction rates of some trans P-substituted epoxybenzalacetopheaones 1[a-h] with thiophenolate and p-nitrothiophenolate have been measured at different temperatures. The reaction is unidirectional and gives W - thioaryloxy-p-substituted acetophenones and p-substituted benzaldehyde. Effect of the substituents has been analysed in terms of Hammett linear free energy relationship. The values of P and activation parameters delta Hz number sign and delta S number sign are in accordance with the proposed bimolecular S[N][2]mechanism

Dissociation of azo-B-diketone in dioxane/water mixtures

The effect of varying the percentage of dioxane and temperature on the pK values of some azo-beta-diketones was studied portestiometrically. The results azo-beta-revealed that the degree of solvation preceeded in accordance with the following order I, II, III, IV. The delta H°, delta G° and delta S° values were evaluted. Evaluation of the isoquilibrium tempratures revealed that for compound I, the dissociation process is entropy and enthalpy controlled while for the other compounds, the process is mainly enthalpy controlled