Design,Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease

Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC₅₀ values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC₅₀ value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC₅₀=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.     

Genetics of barley tiller and leaf development

In cereals, tillering and leaf development are key factors in the concept of crop ideotype, introduced in the 1960 s to enhance crop yield, via manipulation of plant architecture. In the present review, we discuss advances in genetic analysis of barley shoot architecture,focusing on tillering, leaf size and angle. We also discuss novel phenotyping techniques, such as 2 D and 3 D imaging, that have been introduced in the era of phenomics, facilitating reliable trait measurement. We discuss the identification of genes and pathways that are involved in barley tillering and leaf development,highlighting key hormones involved in the control of plant architecture in barley and rice. Knowledge on genetic control of traits related to plant architecture provides useful resources for designing ideotypes for enhanced barley yield and performance.     

Linum persicum: Lignans and placement in Linaceae†

Aryltetralin lignans (podophyllotoxin type) are the main lignan constituents of species belonging to Linum section Syllinum (Linaceae). Linum persicum, a perennial plant native to Iran closely related to L. album, has not yet been studied. To evaluate the lignan profile, fresh plants of L. persicumwere collected and divided into different parts and analyzed by HPLC. The main aryltetralin lignans found inL. persicumplant parts, callus and cell cultures were podophyllotoxin (PTOX), 6-methoxypodophyllotoxin (MPTOX) and - and -peltatin. Furthermore, the systematic relationship between L. persicum and other Linum species are discussed in the light of morphological and phytochemical aspects. Abbreviations: MPTOX – 6-methoxypodophyllotoxin; PTOX – podophyllotoxin; DOP – deoxypodophyllotoxin.     

Simultaneous determination of lipoic acid (LA) and dihydrolipoic acid (DHLA) in human plasma using high-performance liquid chromatography coupled with electrochemical detection

A fast, simple, and a reliable high-performance liquid chromatography linked with electrochemical detector (HPLC-ECD) method for the assessment of lipoic acid (LA) and dihydrolipoic acid (DHLA) in plasma was developed using naproxen sodium as an internal standard (IS) and validated according to standard guidelines. Extraction of both analytes and IS from plasma (250 μl) was carried out with a single step liquid-liquid extraction applying dichloromethane. The separated organic layer was dried under stream of nitrogen at 40°C and the residue was reconstituted with the mobile phase. Complete separation of both compounds and IS at 30°C on Discovery HS C18 RP column (250 mm × 4.6 mm, 5 μm) was achieved in 9 min using acetonitrile: 0.05 M phosphate buffer (pH 2.4 adjusted with phosphoric acid) (52:48, v/v) as a mobile phase pumped at flow rate of 1.5 ml min(-1) using electrochemical detector in DC mode at the detector potential of 1.0 V. The limit of detection and limit of quantification for lipoic acid were 500 pg/ml and 3 ng/ml, and for dihydrolipoic acid were 3 ng/ml and 10 ng/ml, respectively. The absolute recoveries of lipoic acid and dihydrolipoic acid determined on three nominal concentrations were in the range of 93.40-97.06, and 93.00-97.10, respectively. Similarly coefficient of variations (% CV) for both intra-day and inter-day were between 0.829 and 3.097% for lipoic acid and between 1.620 and 5.681% for dihydrolipoic acid, respectively. This validated method was applied for the analysis of lipoic acid/dihydrolipoic acid in the plasma of human volunteers and will be used for the quantification of these compounds in patients with oxidative stress induced pathologies.     

Identification,occurrence, incidence and transmission of phytoplasma associated with Petunia violacea witches’ broom in Iran

A petunia witches’ broom (PvWB) disease, characterized by phyllody, virescence, witches’ broom, little leaf and yellowing, was observed in municipal lands and parks in Bandar Abbas, Hormozgan province, Iran. The disease was present with an average incidence of 20%. PCR and sequencing analysis carried out on selected samples from symptomatic plants showed the presence of a phytoplasma associated with the disease. The molecular comparison of the 16S ribosomal gene indicated 99% sequence identity with the one of “Candidatus Phytoplasma australasia”. This phytoplasma was transmitted to healthy petunia plants under experimental conditions by the leafhopper Orosius albicinctus that was then demonstrated to be a vector of this phytoplasma.     

Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity

A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO₂CH₃ at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone ( 16 ) showed significant COX-2 inhibition (IC₅₀=0.05±0.01 μM), and antiproliferative activity (IC₅₀=5.46±4.71 μM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme.     

Accuracy evaluation of distance inverse square law in determining virtual electron source location in Siemens Primus linac

Aim

The aim of this study is to evaluate the accuracy of the inverse square law (ISL) method for determining location of virtual electron source (S_Vir) in Siemens Primus linac.

Association of mitochondrial dysfunction and lipid metabolism with type 2 diabetes mellitus: A review of literature

Background

Diabetes mellitus (DM) is one of the most prevalent chronic diseases, and its prevalence continues to increase globally. The impact of mitochondrial dysfunction and lipid metabolism on diabetes mellitus and insulin resistance (IR) has been implicated in several previous reports; however, the results of studies are confusing despite four decades of study.

Methods/Results

This review has evaluated updated understanding of the role of mitochondrial dysfunction and lipid metabolism on type 2 diabetes, and found that mitochondrial dysfunction and lipid metabolism disorder induce the dysregulation of liver and pancreatic beta cells, insulin resistance, and type 2 diabetes.

Conclusion

Mitochondrial dysfunction and lipid metabolism induce metabolic dysregulation and finally increasing the possibility of diabetes.