Design, synthesis and anti platelet aggregation studies of new α -phenyl cinnamonitrile derivatives

Introduction:Cardiovascular and thromboembolic diseases are one of the most common causes of death in the world. Platelets play an important role in the pathogenesis of cardiovascular diseases. The use of antiplatelet drugs is one of the most important ways of prevention and treatment cardiovascular disorders. Looking at the various complications of the anti platelet drugs of the old generation, researchers are always looking for new drugs in the field of anti platelet therapy. There are some reports indicating that α-phenyl cinnamonitrile can be useful for treatment of cardiovascular diseases.  Therefore this study is designed to explore the anti platelet activity of a selected group of α-phenyl cinnamonitriles. Methods and Results:Benzyl cyanide and various benzaldehyde derivatives were reacted in 90% ethanol to obtain the title compounds. A solution of sodium methoxide in methanol was added to this mixture dropwise, with stirring.. The product, thus obtained, was filtered off and crystallized from proper solvent. In the next step using hydrolysis of the synthesized derivatives in the presence of TFA, acetic acid and98% sulfuric acid, amide derivatives of the nitrile compounds were synthesized. The structure of the synthesized compounds was confirmed by using NMR, IR, and MS spectrometry methods. Invitro anti platelet activity of α-phenyl cinnamonitriles  and  their amide congeners were evaluated by using arachidonic acid (AA) and adenosine diphosphate (ADP) as inducer according to born method on human platelet rich plasma (PRP). For all compounds IC50s were calculated and compared. The result showed that α-phenyl cinnamonitrile, 4- methoxy-α-phenyl cinnamonitrile, were the most potent anti platelet aggregation agents with IC50 values of 17.79 and 38.2 µM respectively. R=2-Cl; 2-Br; 2-OH; 3-F;3-Cl;3-Br;3-OH; 4-H; 4-OMe;4-F; 4-Cl; 4-CN; 4-Br; 3,4-diOMe ;3, 4, 5-triOMe. Conclusions:A group of α-β unsaturated nitrile derivative is introduced as new anti platelet aggregation agents proving the eligibility of this scaffold for anti platelet activity

Anti-platelet aggregation assay and chemical composition of essential oil from Allium atroviolaceum Boiss growing in Iran.

Plants belonging to genera Allium have widely been acquired as food and medicine. Their wide use was mainly due to the medicinal properties attributed to these plants over the centuries, lately supported by epidemiological and research studies. In this study, essential oil constituents of Allium atroviolaceum growing in Shahr-e-kord, Iran, were investigated through gas chromatography/mass spectrometry (GC-MS) technique. In this essential oil two major constituents were trisulfide, di-2-propenyl (26.85%) and diallyl disulphide (10.98%) while trans-2-(2- pentenyl) furan (0.02%) and Limonene (0.06%) have been identified in lower amounts. The in-vitro antiplatelet activity of essential oil was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results showed that essential oil of Allium atroviolaceum with IC50; 0.25 mg/ml and 0.47 mg/ml inhibited in-vitro platelet aggregation induced by AA and ADP respectively

Synthesis and Preformulation Studies of KTTKS and PAL-KTTKS as Anti-Wrinkle Peptides

Introduction: Skin aging is a complicated process which is one of the major issues in the field of dermatology and cosmetic products. Peptides are one of the novel ingredients included in the anti-aging formulations. KTTKS (Lys-Thr-Thr-Lys-Ser) and its derivative, PAL-KTTKS (Palmitic acid-KTTKS), have attracted a lot of attention in arresting or delaying skin aging, but unfortunately, there are almost no preformulation studies available about them. Methods and Results:Both peptides were synthesized by solid phase peptide synthesis and identified by Mass spectroscopy technique. UV absorption ability, percentage of crystallinity, melting point, decomposition temperature and thermal behavior of both peptides were analyzed by UV spectroscopy, XRD, TGA and DSC techniques respectively. Partition coefficient was also determined by ACD/chemsketch software. In addition stability studies for the aqueous solution of KTTKS were performed at 32 and 37 ℃.  The results of UV spectroscopy showsthe wavelength of maximum absorbance of both peptides is in the vacuum UV range. Based on the results of melting point and TGA apparatuses, KTTKS and PAL- KTTKS decompose at about 154 ℃ and 112 ℃ respectively and there is no melting point for them before decomposition. The results of DSC thermogramsindicate an endothermic peak at the temperature below 60 ℃ for both peptides which is probably due to intrinsic structural rearrangement or evaporation of volatile solvents. Crystallinity percentage for KTTKS and PAL-KTTKS are 62% and 32% respectively. cLogp of KTTKS is -3.27 and cLogp of PAL-KTTKS is 3.32. Conclusions: The results of this investigation can be employed for the formulation of these peptides for TTD

Protein Enrichment of Olive Cake Substrate by Solid State Fermentation of Lentinus edodes

Solid-state fermentation technique can be used for protein enrichment of the olive cake substrate (OCS). Among microorganisms, mushrooms, in particular, white-rot fungi belonging to the genus Lentinus is known for its ability to digest the lignin and also the most effective producers of lignocellulosic enzymes. Hence, the objective of this work is to evaluate the effect of Lentinus edodes on protein content of agro by-product namely, olive cake substrate. To do so, solid state fermentation was performed at 25ºC in different conditions including various nitrogen sources, inoculum size, fermentation time, and moisture content using glass bottle as bioreactor. Protein extraction was carried out at 4ºC. The results obtained show significantly increasing protein content of OCS. HIGHLIGHTS•Solid-state fermentation technique can be used for protein enrichment of the olive cake substrate (OCS).•The nutritional value of olive cake substrate (OCS) was improved upon fungal treatment.•Lentinus edodes fungi enhanced the protein content in experimental OCS

Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods

In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs) with phospholipid-polyethylene glycols (Pl-PEGs) was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations) was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution

Evaluation of Anti-Platelet Aggregation Effect of Some Allium Species

Epidemiologic studies show that the cardiovascular diseases are associated with multiple factors such as raised serum total cholesterol, increased LDL, increased platelet aggregation, hypertension and smoking. In-vitro studies have confirmed the ability of some plants of Allium species to reduce these parameters. Therefore, we evaluated anti-platelet aggregation effect of some Allium species (Allium ampeloprasum, A. hirtifolium, A. haemanthoides, A. vavillovi, A. atroviolaceum, A. jesdianum, A. shelkovnikovii) using arachidonic acid (AA) and adenosine diphosphate (ADP) as platelet aggregation inducers. The screening results for methanolic extract of Allium species showed that the maximum effect of anti-platelet aggregation was related to A. atroviolaceum. This extract inhibited the in-vitro platelet aggregation induced by AA and ADP with IC50 values of 0.4881 (0.4826-0.4937) mg/ml and 0.4945 (0.4137-0.5911) mg/ml respectively. These results support the hypothesis that the dietary intake of Allium could be beneficial for prevention of cardiovascular diseases

Magnetite Nanoparticles Fe3O4for Preconcentration and Determination of Trace Amount of Tamsulosine hydrochloride in Human Plasma

Abstract In the present study, magnetite nanoparticles Fe3O4modified with Cetyltrimethylammonium bromide (CTAB) was successfully prepared and their application as a sorbent in the magnetic-dispersive solid phase extraction(M-dSPE)mode to preconcentration and determination of Tamsulosinhydrochloride (TMS) in human plasma was investigated by coupling with high performance liquid chromatography-ultraviolet detection (HPLC-UV).The influence of sorbent amount, pH of sample solution, extraction and desorption conditions were studied. The maximum adsorption capacity, and qmax, was obtained from Langmuir’s model.The structure, morphology and magnetic properties of adsorbent were characterized using scanning electron microscopy (SEM). Introduction: TMSbelongs to a class of drug called alpha-1(α1) adrenergic receptor antagonists. Since TMS is widely used as an effective α1 blocker, the development and validation of analytical methods for its determination in biological fluids are essential. Many of these methods are however, expensive,toxic, requiring a derivatization step and specific solvent extraction. Based on magnetite nano Fe3O4, a simple, fast and inexpensive, nontoxic M-dSPE method was established. Methods and Results:First the Fe3O4 nanoparticles were synthesized via co-precipitation.Then Fe3O4(3mg) and CTAB 0.02- 4 mL of 0.1 %(w/v) were dispersed into phosphate buffer(pH=7.0) and added to the sample solution.The suspension was vigorously shaken to reach adsorption equilibrium, and the sorbent was subsequently isolated with a strong magnet. After that, the sorbent was eluted with buffer solution of pH 10.0 (100 µL) as the eluent solvent .Finally, the eluate was isolated from the sorbent by a strong magnet, and the supernatant was filtered and 20 μL of filtrate was injected into the HPLC-UV system for analysis in triplicate for each concentration. Conclusions:In this work a magnetite nanoFe3O4- based M-dSPE clean up combined with HPLC-UV developed as a new approach for the efficient determination of trace amount of TMS in plasma samples.This method provided effectively clean extracts and removed interfering peaks from the plasma. Furthermore this method was very fast,convenient,cost effective, nontoxic and with a very low consumption of solvent.Key words: Magnetite Nano Fe3O4, TMS, Human Plasma,M-dSPE. &nbsp

Validation of an analytical method for determination of 13 priority polycyclic aromatic hydrocarbons in mineral water using dispersive liquid-liquid microextraction and GC-MS

Dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography–mass spectrometry (GC–MS) was used for the extraction and determination of 13 polycyclic aromatic hydrocarbons (PAHs) in mineral water samples. In this procedure, the suitable combination of extraction solvent (500 μL chloroform) and disperser solvent (1000 μL acetone) were quickly injected into the water sample (10.00 mL) by Hamilton syringe. After centrifugation, 500 μL of the lower organic phase was dried under a gentle stream of nitrogen, re-dissolved in chloroform and injected into GC-MS. Chloroform and acetone were found to be the best extraction and disperser solvent, respectively. Validation of the method was performed using spiked calibration curves. The enrichment factor ranged from 93 to 129 and the recovery ranged from 71 to 90%. The linear ranges for all the PAHs were 0.10-2.80 ngmL-1. The relative standard deviations (RSDs) of PAHs in water by using anthracene-d10 as internal standard, were in the range of 4-11% for most of the analytes (n = 3). Limit of detection (LOD) for different PAHs were between 0.03 and 0.1 ngmL-1. The method was successfully applied for the analysis of PAHs in mineral water samples collected from Tehran. © 2016 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services

Simultaneous determination of 13 priority polycyclic aromatic hydrocarbons in Tehran’s tap water and water for injection samples using dispersive liquid-liquid micro extraction method and gas chromatography-mass spectrometry

Polycyclic aromatic hydrocarbons (PAHs) are classified as persistent and carcinogenic organic pollutants. PAHs contamination has been reported in water. Many of relevant regulatory bodies such as EU and EPA have regulated the limit levels for PAHs in drinking water. In this study, 13 priority polycyclic aromatic hydrocarbons (PAHs) were determined in tap water samples of Tehran and water for injection. Dispersive liquid-liquid microextraction procedure combined with gas chromatography-mass spectrometry was used for the extraction and determination of PAHs in the samples. Under the optimized conditions, the range of extraction recoveries and relative standard deviations (RSDs) of PAHs in water using internal standard (anthracene-d10) were in the range of 71-90% and 4-16%, respectively. Limit of detection for different PAHs were between 0.03 and 0.1 ngmL-1. The concentration of PAHs in all tap water as well as water for injection samples were lower than the limit of quantification of PAHs. This is the first study addressing the occurrence of PAHs in water for injection samples in Iran using dispersive liquid-liquid micro extraction procedure combined with gas chromatography-mass spectrometry. © 2016 by School of Pharmacy

Simultaneous measurement of lead and cadmium in the milk distributed in Tehran’s schools by differential-pulse anodic stripping voltammetry

Milk is one of the most important foods in the dietary regimen of children which can be contaminated with toxic elements such as lead (Pb) and cadmium (Cd). In this study, the concentrations of Cd and Pb were determined in the milk distributed among school-aged children in Tehran. Differential-pulse anodic stripping voltammetry (DPASV) method using hanging mercury drop electrode (HMDE) was performed.The obtained limit of detection (LOD) and limit of quantification (LOQ) were 0.31 ppb and 1.03 ppb for Pb and 0.09 ppb and 0.32 ppb for Cd, respectively. The concentration of Pb and Cd in the examined milk was 3.34 ± 0.63, and 0.42 ± 0.47 ppb, with recovery range between 85-109% and 91-112%, respectively.The results demonstrated that the levels of Pb and Cd were considerably less than the maximum residue limit (MRL), mentioned by the regulatory organizations