Mohammad Arjmand

Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands

This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM).

Nuclear magnetic resonance-based screening of thalassemia and quantification of some hematological parameters using chemometric methods.

High-resolution (1)H NMR spectroscopy of biofluids is a good representation of metabolic pattern and offers a high potential noninvasive technique for pathological diagnosis. Diagnosis of thalassemia and quantification of some blood parameters can be performed by using (1)H NMR spectra of human blood serum in parallel with chemometric techniques. Spectra of 28 samples were collected from 15 adult male and female thalassemia patients as experimental set and 13 healthy volunteers as control set. Principal component analysis (PCA) as a dimension reduction tool was used for transforming spectra to abstract factors. The abstract factors were introduced to linear discriminant analysis (LDA), which is a common technique for classification, in order to establish adequate model for discrimination of healthy and unhealthy samples. In addition, these abstract factors were used for calibration of some blood parameters using radial basis function neural network (RBFNN) as an artificial intelligence modeling method. Different test sets (left out samples in training algorithm) were used for evaluating the quality and robustness of the built models. PCA abstract factors were employed as input for LDA model and successfully classified all the members of the test sets except one member of third test set. RBFNN also has a good capability for modeling the most of blood parameters according to proposed network parameters optimization procedure. We conclude that (1)H NMR spectroscopy, LDA and RBFNN assisted by PCA provide a powerful method for thalassemia diagnosis and prediction of some blood variants.

A Metabolic Study on Colon Cancer Using 1H Nuclear Magnetic Resonance Spectroscopy

Background. Colorectal carcinoma is the third cause of cancer deaths in the world. For diagnosis, invasive methods like colonoscopy and sigmoidoscopy are used, and noninvasive screening tests are not very accurate. We decided to study the potential of 1HNMR spectroscopy with metabolomics and chemometrics as a preliminary noninvasive test. We obtained a distinguishing pattern of metabolites and metabolic pathways between colon cancer patient and normal. Methods. Sera were obtained from confirmed colon cancer patients and the same number of healthy controls. Samples were sent for 1HNMR spectroscopy and analysis was carried out Chenomex and MATLAB software. Metabolites were identified using Human Metabolic Data Base (HDMB) and the main metabolic cycles were identified using Metaboanalyst software. Results. 15 metabolites were identified such as pyridoxine, orotidine, and taurocholic acid. Main metabolic cycles involved were the bile acid biosynthesis, vitamin B6 metabolism, methane metabolism, and glutathione metabolism. Discussion. The main detected metabolic cycles were also reported earlier in different cancers. Our observations corroborated earlier studies that suggest the importance of lowering serum LCA/DCA and increasing vitamin B6 intake to help prevent colon cancer. This work can be looked upon as a preliminary step in using 1HNMR analysis as a screening test before invasive procedures.

A metabolomic study on the effect of intravascular laser blood irradiation on type 2 diabetic patients.

Intravenous laser blood irradiation (ILBI) is widely applied in the treatment of different pathologies including diabetes mellitus. The aim of this study is to evaluate the effects of ILBI on the metabolites of blood in diabetic type 2 patients using metabolomics. We compared blood samples of nine diabetic type 2 patients, using metabolomics, before and after ILBI with blue light laser. The results showed significant decrease in glucose, glucose 6 phosphate, dehydroascorbic acid, R-3-hydroxybutyric acid, l-histidine, and l-alanine and significant increase in l-arginine level in blood and blood sugar in the patients have reduced significantly (p < 0.05). This study clearly demonstrated a significant positive effect of ILBI on metabolites of blood in diabetic type 2 patients. These findings support the therapeutic potential of ILBI in diabetic patients.

NMR-based metabonomics survey in rats envenomed by Hemiscorpius lepturus venom.

About 1% of scorpion stings in Iran have been reported in cities and more than 5% in rural areas. The genus Hemiscorpous lepturus belongs to the family Hemiscorpiidae that is endemic in the south-western province of Khoozestan and other parts of western Iran. Although this species is responsible for only 10% of the reported stings, it is also responsible for 95% of mortalities. The heavy cytotoxic and neurotoxic venomous effects of scorpion sting may cause serious disorders such as erythema, purpuric changes, bulla, necrosis and ulcer, either alone or in combination. The toxic effects of H. lepturus venom cause vast changes in both primary and secondary metabolites of the victim, which finally lead to death if not treated early enough. Metabolomics is the systematic study of chemical fingerprints resulting from cytotoxic and pathogenic reactions of cells. We studied the toxic mechanism of H. lepturus venom on metabolome profiling of the victims along with biochemical pathways, organs and physiological detectable effects of this venom by the help of (1)H NMR. Our results showed that pyrimidine, histidine and tyrosine metabolisms, and steroid hormone biosynthesis were the most affected pathways. The major action of the crude venom is on the pancreas, and also on the nerve cells, spleen and mitochondria, causing acute seizures, which resemble the early markers of myocardial injury and seizure disorders.

The Effect of Aqueous Extract of Cinnamon on the Metabolome of Plasmodium falciparum Using 1 HNMR Spectroscopy

Malaria is responsible for estimated 584,000 deaths in 2013. Researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. Cinnamon is the bark of a tree with reported antiparasitic effects. Metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. It was decided to determine the mechanism of the effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum in vitro using 1HNMR spectroscopy. Prepared aqueous extract of cinnamon was added to a culture of Plasmodium falciparum 3D7 and its 50% inhibitory concentration determined, and, after collection, their metabolites were extracted and 1HNMR spectroscopy by NOESY method was done. The spectra were analyzed by chemometric methods. The differentiating metabolites were identified using Human Metabolome Database and the metabolic cycles identified by Metaboanalyst. 50% inhibitory concentration of cinnamon on Plasmodium falciparum was 1.25 mg/mL with p < 0.001. The metabolites were identified as succinic acid, glutathione, L-aspartic acid, beta-alanine, and 2-methylbutyryl glycine. The main metabolic cycles detected were alanine and aspartame and glutamate pathway and pantothenate and coenzyme A biosynthesis and lysine biosynthesis and glutathione metabolism, which are all important as drug targets.

Metabolomic profiling of cancer cells to Aloe vera extract by 1HNMR spectroscopy

Abstract Background: The modern life style despite its comforts has made cancer a leading public health problem. As chemotherapeutics has many side effects including resistance, recent attention has focused on plants

A new anti-malarial drug against murine malaria

Eosin B, a common laboratory dye has been earlier reported to have good anti protozoan properties in vitro. We studied this drug for its effect on a murine malaria strain, Plasmodium berghei (Pb) in vivo using different tests. Full suppressive 4 days Peter’s Test was used in infected outbred and inbred mice, using both ip and oral routes. Secondary biological assessment was carried out using dose ranging, ED50 and ED90 values obtained. Eosin B anti malarial activity at 400 Ug/ml given in both the routes was similar to that of artemisine and mice survival rate was double that of control and 3 days more than artemisine. PbGST activity was monitored and it was seen that eosin B lowered this enzyme activity. Eosin B seems to be a promising drug, exhibiting good anti malarial effects in the murine model of disease.

Serum Metabolomic Profiling of Sulphur Mustard-Exposed Individuals Using 1HNuclear Magnetic Resonance Spectroscopy

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard‐exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard‐exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using 1H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard‐exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down‐regulation), bile acid (up‐regulation) and tryptophan (down‐regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard‐induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches.

Corrigendum to “The Effect of Aqueous Extract of Cinnamon on the Metabolome of Plasmodium falciparum Using 1HNMR Spectroscopy”

[This corrects the article DOI: 10.1155/2016/3174841.].