Evaluation of long-heating kinetic process of edible oils using ATR-FTIR and chemometrics tools.

Long thermal oxidative kinetic and stability of four different edible oils (colza, corn, frying, sunflower) from various brands were surveyed with the use of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) combined with multivariate curve resolution-alternative least square (MCR-ALS). Sampling from the heated oils (at 170 °C) was performed each 3 h during a 36-h period. Changes in the ATR-FTIR spectra of the oil samples in the range of 4000-550 cm-1 were followed as a function of heating time. MCR-ALS was utilized to resolve the concentration and spectral profiles of three detected kinetic components. Three variations in resolved concentration profiles were related to the thermal-deduction of triacylglycerol of unsaturated acid, appearance of hydroperoxides form of triacylglycerols and generation of secondary oxidation products. The kinetic profiles of these species were dependent on the type of oil. The proposed method can define a new way to monitor the oils' quality.

A validated dispersive liquid-liquid microextraction method for extraction of ochratoxin A from raisin samples.

A method based on dispersive liquid-liquid microextraction (DLLME) was developed for the quantitative extraction of Ochratoxin A (OTA) from raisin samples. The influence of various parameters on the recovery of OTA such as type and volume of DLLME extractant, centrifuging and sonication time, also volume of deionized water was investigated. Recovery values under the optimum conditions were between 68.6 and 85.2 %, the inner and intra-day precision expressed as relative standard deviation (RSD%, n = 3), were less than 15 % at spiking levels of 2.5-30 µg kg(-1). Linearity was studied from 0.5 to 30 µg L(-1), and the limits of detection (LOD) and quantification (LOQ) were 0.7 and 2.0 µg kg(-1), respectively. Real samples were analyzed by DLLME method and compared with confirmative immunoaffinity Column Chromatography (IAC) clean-up. Low cost, simplicity of operation, speed and minimum consumption of organic solvent were the main advantages of proposed method. The mean contamination of samples was 0.88 µg kg(-1) that was lower than European Legal Limit.

Design and synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridines as small molecule BACE-1 inhibitors.

Alzheimer disease (AD) is a neuronal dementia for which no treatment has been consolidated yet. Major pathologic hallmark of AD is the aggregated extracellular amyloid-ß plaques in the brains of disease sufferers. Aß-peptide is a major component of amyloid plaques and is produced from amyloid precursor protein (APP) via the proteolysis action. An aspartyl protease known as ß-site amyloid precursor protein cleaving enzyme (BACE-1) is responsible for this proteolytic action. Distinctive role of BACE-1 in AD pathogenesis has made it a validated target to develop anti-Alzheimer agents. Our structure-based virtual screening method led to the synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine BACE-1 inhibitors (6a-6p; in vitro hits). Molecular docking and DFT-based ab initio studies using B3LYP functional in association with triple-ζ basis set (TZV) proposed binding mode and binding energies of ligands in the active site of the receptor. In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer (FRET) assay. Most of the synthesized dihydropyridine scaffolds were active against BACE-1 while 6d, 6k, 6n and 6a were found to be the most potent molecules with IC50 values of 4.21, 4.27, 4.66 and 6.78 µM, respectively. Superior BACE-1 inhibitory activities were observed for dihydropyridine derivatives containing fused/nonfused thiazole containing groups, possibly attributing to the additional interactions with S2-S3 subpocket residues. Relatively reliable correlation between calculated binding energies and experimental BACE-1 inhibitory activities was achieved (R(2)=0.51). Moreover, compounds 6d, 6k, 6n and 6a exhibited relatively no calcium channel blocking activity with regard to nifedipine suggesting them as appropriate candidates for further modification(s) to BACE-1 inhibitory scaffolds.

Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-ß and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: a randomized, double-blind and placebo-controlled study.

OBJECTIVE: End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-ß (TGF-ß) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-ß. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-ß, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy. MATERIAL AND METHODS: A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months. RESULTS: Serum levels of TGF-ß and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial. CONCLUSION: Short-term turmeric supplementation can attenuate proteinuria, TGF-ß and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.

The effect of the methanol extract of Galium mite on the cellular immunity and antibody synthesis.

In the present study, the immunomodulatory effects of Galium mite, a native herb used for the treatment of inflammation in Iranian traditional medicine, was investigated. The methanolic extract of the plant was prepared and examined for in vivo cell-mediated and humoral immunity against antigen in mice. Galium mite stimulated delayed type hypersensitivity at lower concentrations and inhibited the reaction at higher ones (p < 0.05). A dose-related decrease in primary and secondary antibody titer was observed in mice treated with the extract (p < 0.006). The extract at higher concentrations significantly reduced the proliferation of human-activated lymphocytes (p < 0.001). Cell cycle analysis on human lymphocytes treated with the extract showed an increase in the number of cells in sub-G1 region, indicating the ability of the extract to induce apoptosis in these cells. Induction of apoptosis was confirmed by DNA laddering on gel electrophoresis. In conclusion, G. mite has the ability to modulate cellular and humoral immune responses to the antigenic challenge and affect the rate of cell proliferation due to induction of apoptosis in the lymphocytes.

Effects of Anethum graveolens L. on fertility in male rats.

OBJECTIVES: The effects of Anethum graveolens seed extract on fertility of male rats were investigated. METHODS: Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured. RESULTS: No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups. CONCLUSION: Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition.

A comparative study of the antibacterial, antifungal and antioxidant activity and total content of phenolic compounds of cell cultures and wild plants of three endemic species of Ephedra.

Investigations were carried out to determine antimicrobial and antioxidant properties and total phenol content of three wild species of Ephedra compared with their respective callus cultures. Callus induction was performed in a standard Murashige and Skoog (MS) medium with the following hormonal ranges (mg/L) for every species NAA:1.5, Kin:1 for Ephedra strobiliacea, NAA:2, Kin:1 for Ephedra procera and NAA:2, Kin:0.5 for Ephedra pachyclada. These ranges of PGPR (Plant Growth Promote Regulators) were chosen based on callus induction rates, RGR (Relative Growth Rate) and their fresh weights. An antimicrobial test against five gram negative and two gram positive bacteria and two fungi was performed using the disc diffusion method. All methanolic extracts showed antimicrobial activity, but the antimicrobial activity of the callus cultures was lower than those of the wild plants. E. strobilacea showed the highest antimicrobial activity, and all methanolic extracts of the wild plants and callus cultures unexpectedly showed the highest antimicrobial activity against Pseudomonas aeruginosa. A FRAP (Ferric Reducing Antioxidant Power) test was conducted to evaluate extracts for antioxidant activity. E. strobilacea with 1.61 +/- 0.08 mmol eq quercetin/g extract and 0.278 +/- 0.02 mmol eq quercetin/g extract for the wild plant and callus, respectively, showed the highest results.The total phenol content of extracts was measured by a Folin Ciocalteau test. All the chosen species displayed phenol contents but E. strobilacea had the highest amount (504.9 +/- 41.51 micromol eq catechin/g extracts and 114.61 +/- 15.13 micromol eq catechin/g extracts for the wild plants and callus, respectively).

Immunomodulatory activities of various medicinal plant extracts: effects on human lymphocytes apoptosis.

Plant extracts have been widely evaluated for biological properties. In the present study extracts of several native plants in Iran was investigated for their possible immunomodulatory effects. Peripheral blood lymphocytes separated from healthy individuals were stimulated with phytohemagglutinin (PHA) and cultured with different concentrations of the extracts. Comparison of the cell proliferation in treated cultures showed the highest inhibitory effect due to exposure with Linum persicum. This extract caused a strong dose-dependent decrease in lymphocyte proliferation (p < 0.001). Lymphocytes treated with Cirsium bracteosum were inhibited in a dose dependent manner (SI range 0.9-0.2). Similarly, Echinophora cinerea-treated lymphocytes showed a significant reduction in proliferation compared to that in non-treated cells. Among the extracts, Dionysia termeana, Salvia macrociphon and Ferulago angulata had a mild stimulatory effect on the lymphocytes at concentrations less than 1 microg/ml (p < 0.05). At higher doses all these extracts showed significant inhibitory effects on the proliferation of PHA-treated cells (SI range 0.81 to 0.04). In cell cycle analysis performed by flow cytometry, the strongest appearance of apoptotic cells at sub-G1 phase in various extract-treated cultures was found for D. termeana (14.6 +/- 0.5%). The Percentage of cells undergoing apoptosis in cultures treated with L. persicum was more than 11 compared to that of the control (1.7 +/- 0.08). In DNA analysis, D. termeana and L. persicum showed typical DNA laddering, indicating that these extracts induced apoptosis of lymphocytes. In conclusion, all the extracts studied showed lymphocyte inhibitory effects at high concentrations. These inhibitory effects for some of the plants seem to be due to induction of apoptosis.

Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents.

Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R=3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC=1 micromol/ml) with reference compound isoniazide (INH) (MIC=1 micromol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.

Cytotoxic activity and cell cycle analysis of quinoline alkaloids isolated from Haplophyllum canaliculatum Boiss.

Bioassay-guided fractionation of Haplophyllum canaliculatum Boiss. (Rutaceae) extract resulted in isolation of five quinoline alkaloids: 7-isopentenyloxy-gamma-fagarine, atanine, skimmianine, flindersine and perfamine. This is the first isolation of these compounds from this endemic species. The antitumor activity of these five isolates was evaluated against RAJI, Jurkat, KG-1a, HEP-2, MCF-7, HL-60 and HL-60/MX1 tumor cell lines. The highest cytotoxic effect was observed on acute lymphoblastic leukemia cell lines. 7-Isopentenyloxy-gamma-fagarine, atanine, skimmianine and flindersine exhibited very high cytotoxicity against the RAJI cell line with IC(50) values of 1.5, 14.5, 15.6 and 14.9 microg/mL, respectively and 7-isopentenyloxy-gamma-fagarine, atanine and skimmianine exhibited very high cytotoxicity against the Jurkat cell line with IC(50) values of 3.6, 9.3 and 11.5 microg/mL, respectively. 7-Isopentenyloxy-gamma-fagarine was also highly cytotoxic against the MCF-7 cell line (IC(50) = 15.5 microg/mL), while atanine, skimmianine, flindersine and perfamine showed moderate to low activity against these cells. All alkaloids had moderate to low cytotoxicity against KG-1a and HEP-2. Investigation of the toxic potential of the alkaloids on HL-60 and HL-60/MX1 showed a significantly higher effect against HL-60/MX1, a multidrug-resistant cell line, compared with the control etoposide (p < 0.05). In all cytotoxicity experiments, peripheral blood mononuclear cells (PBMC) were used as a control for normal hematopoietic cells. Flow cytometry analysis of the compounds resulted in the arrest of cell cycle progression at the sub-G1 phase of the RAJI and Jurkat cell lines in a dose-dependent manner. According to computational analyses, the similar cytotoxic trend in the cell lines could be indicative of the fact that these compounds may act through parallel mechanisms.

Spectrophotometric monitoring of nimesulide photodegradation by a combined hard-soft multivariate curve resolution-alternative least square method.

Nimesulide, a Cox-2 inhibitor anti-inflammatory drug, is a light sensitive compound and its biological activity is decreased upon photodegradation. The photodegradation kinetic of nimesulide was investigated spectrophotometrically using multivariate curve resolution analysis to overcome spectral overlapping of reactant and degradation products. The absorbance spectra of the nimesulide methanolic solution, exposed to daily sunlight, were recorded at different times. Three absorbing chemical species, coexisted in the reaction system, were detected by application of factor analysis to the absorbance data matrix. The soft-modeling multivariate curve resolution-alternative least square (MCR-ALS) analysis of the evolutionary absorbance data revealed that nimesulide undergoes photodegradation through a two-step consecutive manner, where both steps obey first-order kinetic. By application of the kinetic hard model constraint to the MCR-ALS analysis, an excellent agreement was obtained between the fitted concentration profiles and those obtained by soft method. The first-order rate constants of the first and second degradation products were calculated as 0.052 (+/-0.007) and 0.009 (+/-0.001)h(-1), respectively. Finally, the pure spectra of the resolved chemical species were calculated, where that of nimesulide was the same as that obtained experimentally.

Application of a self-modeling curve resolution method for studying the photodegradation kinetics of nitrendipine and felodipine.

Dihydropyridine (DHP) derivatives, as calcium channel blockers with cardiovascular activity, are highly photosensitive and converted in the presence of light to compounds that are inactive. In this work, a self-modeling curve resolution method was applied to study the photodegradation kinetics of nitrendipine and felodipine by spectrophotometric method. The methanolic solutions of drugs were separately exposed to UV and daylight, respectively. A fully soft-modeling multivariate curve resolution method based on the combination of iterative target transformation and Kubista methods were used to analyze the recorded absorbance data, extracting the concentration profiles and pure spectra of the drugs and their photodegradation products. By fitting the concentration profiles of the studied DHP drugs to different kinetic equations, it was found that at the beginning of lighting, the reaction is zero-order and in the case of nitrendipine it changes to a first-order kinetic when the concentration of products exceeded than that of the initial compounds.

Design and synthesis of new symmetrical derivatives of dihydropyridine containing a pyridyl group on the 3, 5-positions and evaluation of their cytotoxic and multidrug resistance reversal activity.

Today, chemotherapy is an important part in the treatment of several kinds of cancer; however, the development of drug resistance remains one of the major obstacles in successful chemotherapy. Several types of agents have been recognized as multidrug resistance (MDR) inhibitors, among which the 1,4-dihydropyridines (DHPs) have been investigated the most. P-glycoprotein inhibition has been reported as the main MDR reversal mechanism of DHPs, whilst other mechanisms such as inhibition of topoisomerase II have received less attention. Therefore, in this study new derivatives of DHP have been synthesized. Their cytotoxic activity and their effects in reversing atypical MDR have been evaluated. The results confirmed the appropriate effect of these compounds on atypical MDR. Although it was observed that these compounds had a moderate cytotoxic effect, the cytotoxicity of one compound on the K562 cell line (IC50 = 6.61 microM) was comparable with that of doxorubicin (IC50 = 4.17 microM). Finally, the Ca(2+)-channel antagonistic activity, an undesired effect for these compounds, was evaluated.

Calycopterin, an immunoinhibitory compound from the extract of Dracocephalum kotschyi.

Medicinal plants have been widely investigated for their various effects. Dracocephalum kotschyi Boiss (Labiatae) is used in Iranian traditional medicine for the treatment of rheumatoid diseases. The inhibitory effect of D. kotschyi on the lectin-induced cellular immune response has been demonstrated previously. In this study, mitogen-treated lymphocytes were exposed to the extract of D. kotschyi and analysed for the induction of apoptosis using flow cytometry and gel electrophoresis. The data obtained indicated a dose-dependent increase of cells in the sub-G1 phase of cell cycle. Study of internucleosomal DNA fragmentation showed a typical DNA laddering in agarose gels. A bioactivity-guided fractionation assay to find the active components responsible for the inhibitory effect of D. kotschyi on mitogen-induced lymphocyte proliferation led to the isolation of calycopterin from the ethyl acetate extract of D. kotschyi. Its structure was identified by spectroscopic methods including( 1)H-NMR, (13)C-NMR, MS and UV spectra. Calycopterin inhibited lymphocyte proliferation in a dose-dependent manner with an IC(50) value of 1.7 microg/mL. In conclusion, the results of this study suggest that D. kotschyi extract has the capacity to induce apoptosis in the lymphocytes and that isolated calycopterin is responsible for the inhibitory effect of D. kotschyi on lymphocyte proliferation.

Antitumor activity and apoptosis induction in human cancer cell lines by Dionysia termeana.

Studies have demonstrated that plant extracts possess various biological effects including antitumor activity. In the present study, the antitumor activity of Dionysia termeana, a plant native to Iran, was investigated. Cytotoxic activity of the extract on tumor cell lines using MTT colorimetric assay was determined. Cell cycle analysis by flow cytometry and DNA fragmentation analysis on sensitive cell lines was then carried out. Results obtained indicated that the highest activity of D. termeana was against K562 leukemia cell line with IC50 less than 20 microg/mL. Fifty-five percent inhibition of Jurkat cells due to exposure to D. termeana was found at 200 microg/mL of the extract. A549, a lung carcinoma cell, and Fen bladder carcinoma cell line were less affected. In flow cytometry analysis, D. termeana induced apoptosis in the K562 and Jurkat cells. In DNA fragmentation analysis the extract produced ladder formation in both cells. In conclusion, these results indicated that the extract used in this study have antitumor activity through induction of apoptosis particularly in the leukemia cell lines.

Induction of apoptosis in leukemia cell lines by Linum persicum and Euphorbia cheiradenia.

PURPOSE: In the present study two medicinal herbs Linum persicum and Euphorbia cheiradenia that are native to Iran were tested for their possible anticancer effect and induction of apoptosis on human tumor cell lines including leukemia cell lines. METHODS: The effect of methanolic extracts of the herbs on the inhibition of cell proliferation was assessed by MTT colorimetric assay. K562 and Jurkat cell lines treated with the extracts were analyzed for the induction of apoptosis by flow cytometry using propidium iodide staining. DNA fragmentation analysis was performed. RESULTS: Various concentrations of L. persicum and E. cheiradenia showed inhibitory effects on different cell lines. Two leukemic lines including K562 and Jurkat were the most sensitive cells for L. persicum with IC50 of 0.1 and 10 mug/ml, respectively. In the cultures of tumor cell lines treated with E. cheiradenia, the main inhibitory effects was for Jurkat cells with IC50 of 12.5 microg/ml. Results indicated a dose-dependent accumulation of cells in the sub-G1 phase. Study of internucleosomal DNA fragmentation showed a typical DNA laddering in agarose gels for both extracts. CONCLUSION: The present study showed cytotoxic activity of both herbs on tumor cell lines and suggests that this effect may in part be due to the induction of apoptosis in leukemic cells.

HPLC method for analysis of a new 1,4-dihydropyridine: application to pharmacokinetic study in rabbit.

A high sensitive HPLC assay for plasma analysis of a new 1,4-dihydropyridine (nitrimidodipine) was developed to support the subsequent preclinical development of the compound. To 1 ml of rabbit plasma was added internal standard (3-(4-nitrooxy butyl)-5-ethyl-1,4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl)-3,5-pyridine dicarboxylate) and 0.5 ml of 1M HCl. The plasma was extracted using 5 ml ethyl acetate which evaporated under gentle stream of nitrogen. The residue was reconstituted in 200 microl mobile phase and 100 microl of aliquots were injected to HPLC system. Chromatographic separation was accomplished on octadecyl column (250 mm x 4.6mm) using a mobile phase consisting of acetonitrile-water (45:55, v/v). The method was sensitive to 2.5 ng/ml in plasma (LOD), acceptable within- and between day reproducibility and a linearity (r2>0.9957) over a concentration range from 5 to 400 ng/ml. The mean extraction efficacy was 90.6% and no interfering peaks of the blank plasma chromatograms were observed. By using the above procedure, a simple, sensitive and convenient HPLC assay for determination, stability evaluation and pharmacokinetic study of nitrimidodipine was developed.

Simultaneous Chloramphenicol and Florfenicol Determination by A Validated DLLME-HPLC-UV Method in Pasteurized Milk.

The antibiotic residues in milk are a well-known serious problem and pose several health hazards to consumers. We have described a simple, rapid, and inexpensive DLLME-HPLC/UV technique for the extraction of chloramphenicol and florfenicol residues in milk samples. Under the optimum conditions, linearity of the method was observed over the range 0.02-0.85 µg/L with correlation coefficients > 0.999. The proposed method has been found to have a good limit of detection (signal to noise ratio = 3) for chloramphenicol (12.5 µg/Kg) and florfenicol (12.2 µg/Kg), and precision with relative standard deviation values under 15% (RSD, n = 3). Good recoveries (69.1-79.4%) were obtained for the extraction of the target analytes in milk samples. This simple and economic method has been applied for analyses of 15 real milk samples. Among all samples only one of them was contaminated to florfenicol; 62.4 µg/Kg and contamination to chloramphenicol was not detected.

Biotransformation of acetoin to 2,3-butanediol: Assessment of plant and microbial biocatalysts.

2,3-Butanediol (2,3-BD) is a valuable bulk chemical owing to its extensive application in chemical and pharmaceutical industry with diverse applications in drug, cosmetics and food products. In the present study, the biotransformation of acetoin to 2,3-BD by five plant species (Brassica oleracea, Brassica rapa, Daucuscarota, Pastinaca sativa, and Raphnussativus) and five microorganisms (Aspergillusfoetidus, Penicillumcitrinum, Saccharomyces carlbergensis, Pichiafermentans, and Rhodotrulaglutinis) was investigated as a method for the production of 2,3-BD, which can serve as an alternative to the common pentoses and hexoses fermentation by microorganisms. The produced 2,3-BD stereoisomers were characterized and their total conversion yields were determined. The results showed that the examined plants can be used as a green factory for the production of all 2,3-BD stereoisomers, except B. rapa. In microorganisms, P. fermentans and S. carlbergensis produced (-)-2R,3R and mesobutanediol, while P. citrinum produced (+)-2S,3S and mesobutanediol. R. glutinis and A. foetidus produced all three isomers. In conclusion, efficient whole-cell biocatalysts from plants and microorganisms were determined in the bioconversion of acetoin to 2,3-BD. The profile of produced stereoisomers demonstrated that microorganisms produce more specific stereoisomers.

Inhibitors of Alzheimer's BACE-1 with 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structure.

ß-site amyloid precursor protein cleaving enzyme (BACE-1) is a validated target for Alzheimer therapy due to its distinctive role in pathogenesis of AD. In the present contribution, a series of new 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine structures were synthesized as BACE-1 inhibitors (6a-6n). In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer assay. Synthesized dihydropyridine (DHP) analogues exhibited weak to good inhibitory activities while 6i, 6n and 6a were found to be the most potent molecules with 83.76, 79.45 and 72.47 % BACE-1 inhibition at 10 µM, respectively. Structure binding/activity relationship elucidations revealed that superior BACE-1 inhibitory activities were observed for DHP derivatives bearing fused/non-fused thiazole groups and particularly 3,5-bis-N-(6-ethoxy-2-benzothiazolyl) moiety. Binding maps showed that enhanced activity may be attributed to the additional H-bond and hydrophobic interactions with S2-S3 subpockets of BACE-1.