Development of a Sensitive and Rapid Method for Determination of Acrylamide in Bread by LC-MS/MS and Analysis of Real Samples in Iran IR.

A new sample preparation procedure and a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method were developed for the quantitative analysis of acrylamide in bread. The method is based on sample extraction in methanol, purification with Carrez solutions and clean- up with Primary Secondary Amine (PSA).The developed method offers an efficient, inexpensive, easy sample preparation and very sensitive procedure for determination of acrylamide in bread. The use of spiked calibration curves for constructing the calibration curve substantially reduced adverse matrix-related effects. Recoveries were between 96 and 105.3%. Good results were obtained with respect to repeatability (RSDs <11%). The limit of detection and quantification of the method was 0.3 and 1 ng/g, respectively, which shows the method is very sensitive. The developed method was used for the determination of acrylamide in 26 traditional bread samples (Sangak) collected from Shiraz. The results showed that about 96% of Sangak bread samples were contaminated with acrylamide that 64.3 and 33.3 of semi-industrial and traditional Sangak bread were higher than benchmark levels (50 µg/kg), respectively. There are a few reports concerning contamination of Sangak bread samples with acrylamide in Iran. Therefore, this method could be used for a comprehensive survey of acrylamide in Sangak bread samples in the country.

Health risk assessment of acrylamide in bread in Iran using LC-MS/MS.

Acrylamide is a chemical, often present in bread, legally classified as carcinogen, mutagen and reproductive toxicant. Since bread is consumed both world-wide and in Iran, determination of acrylamide in different types of breads is of high interest. In the present study, acrylamide was monitored in 56 Sangak and 30 industrial bread samples collected from Tehran and Shiraz, using LC-MS/MS (LOQ = 1 ng/g). In addition, the noncarcinogenic risk (target hazard quotient-THQ) and carcinogenic risk (incremental lifetime cancer risk-ILCR) due to ingestion of acrylamide through bread consumption in children and adults were assessed. Acrylamide was detected in more than 90% of the samples tested. The average daily intake of acrylamide in Iran based on exclusive consumption of Sangak bread, was estimated at 145 ng/kg bw/day. Based on the THQ for bread acrylamide in adults and children, the decreasing risk order was: Shiraz semi-industrial Sangak, Shiraz traditional Sangak, Tehran traditional Sangak, Tehran industrial bread. The ILCR of bread acrylamide calculated for adults and children was higher than the permissible lifetime carcinogenic risk value established by USEPA (1.00E-5). Results show that bread is a major source of acrylamide intake by people in Iran and all consumers regardless of age could be at elevated carcinogenic risk.

Rational Design and Synthesis of 1-(Arylideneamino)-4-aryl-1H-imidazole-2-amine Derivatives as Antiplatelet Agents.

Based on previous studies indicating the pharmacophoric role of a hydrazone group and azole rings for antiplatelet aggregation activity, a few series of compounds with both hydrazone and an azole (imidazole) ring in their structures were synthesized, and their platelet aggregation inhibitory effects were evaluated. Two of these 1-(arylideneamino)-4-aryl-1H-imidazole-2-amine derivatives, compounds 4 a [(E)-1-(benzylideneamino)-4-phenyl-1H-imidazol-2-amine] and 4 p [(E)-4-phenyl-1-((thiophen-2-ylmethylene)amino)-1H-imidazol-2-amine], exhibited IC50 values similar to that of acetylsalicylic acid against collagen as a platelet aggregation inducer. Structural comparison of the synthesized compounds revealed that those with a para-substituted phenyl ring on the imidazole were among the most active compounds against platelet aggregation induced by arachidonic acid (AA), and the presence of a thiophene ring in these compounds maximized their antiplatelet activity.

N-substituted indole carbohydrazide derivatives: synthesis and evaluation of their antiplatelet aggregation activity.

BACKGROUND: Platelet aggregation is one of the most important factors in the development of thrombotic disorders which plays a central role in thrombosis (clot formation). Prophylaxis and treatment of arterial thrombosis are achieved using anti-platelet drugs. In this study, a series of novel substituted indole carbohydrazide was synthesized and evaluated for anti-platelet aggregation activity induced by adenosine diphosphate (ADP), arachidonic acid (AA) and collagen. METHODS: Our synthetic route started from methyl 1H-indole-3-carboxylate (1) and ethyl 1H-indole-2-carboxylate (4) which were reacted with hydrazine monohydrate 99%. The aldol condensation of the later compound with aromatic aldehydes led to the formation of the title compounds. Sixteen indole acylhydrazone derivatives, 3d-m and 6d-i were tested for anti-platelet aggregation activity induced by adenosine diphosphate (ADP), arachidonic acid (AA) and collagen. RESULTS: Among the synthesized compounds, 6g and 6h with 100% inhibition, proved to be the most potent derivatives of the 2-substituted indole on platelet aggregation induced by AA and collagen, respectively. In 3-substituted indole 3m with 100% inhibition and 3f and 3i caused 97% inhibition on platelet aggregation induced by collagen and AA, respectively. CONCLUSION: In this study, compounds 6g, 6h, 3m, 3f and 3i showed better inhibition on platelet aggregation induced by AA and collagen among the title compounds. Quantitative structure-activity relationship (QSAR) analysis between the structural parameters of the investigated derivatives and their antiplatelet aggregation activity was performed with various molecular descriptors but, analysis of the physicochemical parameters doesn't show a significant correlation between the observed activities and general molecular parameters of the synthesized derivatives. Although, due to the existence of several receptors on the platelets surface which are responsible for controlling the platelet aggregation, the investigated compounds in the present study may exert their activities through binding to more than one of these receptors and therefore no straight forward SAR could be obtained for them.

Synthesis and Molecular-cellular Mechanistic Study of Pyridine Derivative of Dacarbazine.

Dacarbazine is an antitumor prodrug which is used for the treatment of malignant metastatic melanoma and Hodgkin's disease. It requires initial activation in liver through an N-demethylationreaction. The active metabolite prevents the progress of disease via alkylation of guanine bases in DNA strands. In order to investigate the importance of imidazole ring and its dynamictautomerization in anticancer activity of dacarbazine, a pyridine analog of this drug was synthesized and the cytotoxic activity and cellular-molecular mechanisms of action for this compound were compared with those of dacarbazine. EC50 values for dacarbazine and the pyridine analog were found to be 56 µM and 33 µM respectively. Both dacarbazine and the pyridine analog resulted in formation of reactive oxygen species (ROS) upon their addition to the isolated rat hepatocytes. They also decreased the mitochondrial membrane potential and causedlysosomal membrane rupture. Cytotoxicity was prevented by ROS scavengers and antioxidants. Cytotoxicity wasalso prevented by CYP450 inhibitors, lysosomalinactivators and MPT (Mitochondrial Permeability Transition Pore) blockers.

Electrochemical synthesis of novel 1,3-indandione derivatives and evaluation of their antiplatelet aggregation activities.

Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway.

Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents.

BACKGROUND: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest. METHODS: This study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides. RESULTS: All the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity. CONCLUSIONS: Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.

A simple electrochemical method for the rapid estimation of antioxidant potentials of some selected medicinal plants.

Clinical and Epidemiological studies have shown that a diet rich in fruits and vegetables is associated with a decreased risk of cardiovascular diseases, cancers and other related disorders. These beneficial health effects have been attributed in part to the presence of antioxidants in dietary plants. Therefore screening for antioxidant properties of plant extracts has been one of the interests of scientists in this field. Different screening methods have been reported for the evaluation of antioxidant properties of plant extracts in the literature. In the present research a rapid screening method has been introduced based on cyclic voltammetry for antioxidant screening of some selected medicinal plant extracts. CYCLIC VOLTAMMETRY OF METHANOLIC EXTRACTS OF SEVEN MEDICINAL PLANTS: Buxus hyrcana, Rumex crispus, Achillea millefolium, Zataria multiflora, Ginkgo biloba, Lippia citriodora and Heptaptera anisoptera was carried out at different scan rates. Based on the interpretation of voltammograms, Rumex crispus, Achillea millefolium and Ginkgo biloba showed higher antioxidant capability than the others while Lippia citriodora contained the highest amount of antioxidants. Cyclic voltammetry is expected to be a simple method for screening antioxidants and estimating the antioxidant activity of foods and medicinal plants.