Phytochemical investigation on Euphorbia macrostegia [Persian wood spurge]

Euphorbia macrostegia or Persian wood spurge is one of the seventeen endemic plants of this genus in Iran. Three triterpenoids, 24-methylenecycloartan-3 beta -ol [1], butyrospermol [2] and cycloartenol [3] and three diglycerides, 1,2-di-O- alpha -linolenoyl-sn-glycerol [4], 1-O-linoleoyl-3- O-palmitoyl-sn-glycerol [5] and 1-O- alpha -linolenoyl-2-O-palmitoyl-sn-glycerol [6] were isolated from the hexane soluble part of methanol-dichloromethane extracts of the aerial parts of Euphorbia macrostegia Boiss. The structures of all compounds were elucidated using different spectroscopy methods including, [1]H NMR, [13]C NMR, HSQC, HMBC, EI-MS and IR. The triterpenes and the unsaturated fatty acids moieties of the diglycerides isolated from the plant were reported previously to have analgesic, anticancer, bactericidal and antifungal activity. Here, we show that E. macrostegia is a new source for the above mentioned biologically active compounds

Ab-initio and conformational analysis of a potent vegfr-2 inhibitor: a case study on motesanib

Vascular endothelial growth factor receptor-2 [VEGFR-2]; a cell surface receptor for vascular endothelial growth factors, is a key pharmacological target involved in the cell proliferation/angiogenesis. It has been revealed that VEGFR-2 induces proliferation through activation of the extracellular signal-regulated kinases pathway. In this regard, targeting the VEGFR-2 has been considered as an efficient route to develop anti-tumor agents. Motesanib is a small-molecule antagonist of VEGFR-1, 2, and 3 [IC50s; 2 nM, 3 nM, 6 nM, respectively]. It is an experimental drug candidate undergoing clinical trials against some types of cancer. In the present study, Motesanib [AMG 706] was evaluated in terms of its binding energies with individual amino acids of VEGFR-2 active site [amino acid decomposition analysis]. For this purpose, functional B3LYP associated with split valence basis set using polarization functions [Def2-SVP] was used. Comparative Conformational analysis of the ligand in optimized and crystallographic states revealed that Motesanib does not necessarily bind to the VEGFR-2 active site in its minimum energy conformer

Oxidative aromatization, cytotoxic activity evaluation and conformational study of novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8[9H, 12H]-dione derivatives

In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8[9H, 12H]-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12-tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized compounds was assessed on three different human cancer cell lines [K562, LS180, and MCF-7]. Synthesized compounds showed moderate cytotoxic activities. The most active one apeared to be 2e, containing a methoxy group on the meta position of phenyl ring [IC50 range in different cell lines: 11.1-55.7 Micro M]. Furthermore; comparison of the cytotoxic activity of these novel oxidized derivatives with non-oxidized counterparts revealed that oxidation of dihydropyridine ring to pyridine, improves the activity especially in LS180 cell line. Conformational analysis revealed that some conformational aspects of oxidized derivatives such as orientation of C7-aryl substitute were clearly different from non-oxidized ones

Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in rat models

Wounds and wound healing have always been one of the most important subjects that experimental researches were dedicated to. Simvastatin has been used for long as a common lipid lowering agent which was reported to have some pleiotropic effects such as antioxidation, anti-inflammation and immunomodulation. In this study we aimed to determine the effect of simvastatin on wound healing process in laboratory rats by means of stereological and histopathological analyses. 36 male Sprague-Dawley rats [220 +/- 20 g] with a 1 cm[2] circular full-thickness wound on their back were divided into three groups: SS group that received a gel with 2% concentration of simvastatin; UW group that received no treatment but daily irrigation with normal saline; Base group that was treated with the gel base. Duration of the study was 12 days and at the end, wound closure rate, grade of inflammation, granulation-tissue formation, ulceration, epithelization, fibroblast proliferation, collagen-bundles synthesis, and vascularization were determined. Outcome of this study revealed that Simvastatin improves the wound healing by its anti-inflammatory and epithelization induction effect as well as statistically significant induction of fibroblast proliferation and collagen bundle synthesis which were reported by our stereological and histopathological investigations. Results of the present study demonstrated that topical Simvastatin enhances the wound healing process through affecting different aspects of tissue regeneration; however, further researches are needed to find the exact mechanism, advantages and disadvantages of this chemical agent

Cytotoxic, antioxidant and antimicrobial activities and phenolic contents of eleven salvia species from Iran

The plants of the genus Salvia synthesize several types of secondary metabolites with antimicrobial, cytotoxic, and radical scavenging activities and are used in the folk medicine of different countries. Eleven Salvia species including S. aegyptiaca, S. aethiopis, S. atropatana, S. eremophila, S. hypoleuca, S. limbata, S. nemorosa, S. santolinifolia, S. sclarea, S. syriaca, and S. xanthocheila were collected from different localities in Iran and screened for their cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] colorimetric assay. The antioxidant potential and total phenol contents of the plant extracts were assessed by 2,2-diphenyl-l-picrylhydrazyl [DPPH] radical scavenging assay and Folin-Ciocalteu reagent respectively and finally antimicrobial activity of the above extracts were determined by using agar disc diffusion [ADD] and nutrient broth micro-dilution [NBMD] bioassays. Cytotoxic activity of methanol, 80% methanol and dichloromethane extracts of these plants were assessed on 3 human cancer cell lines. All of the extracts of S. eremophila and S. santolinifolia were active at IC[50] values of 10.5-75.2 microg extract/mL, while the methanol and dichloromethane extracts of S. limbata, S. hypoleuca and S. aethiopis showed considerable cytotoxic activity against the tested cell lines. Among the tested plants for their antioxidant activity, S. nemorosa, S. atropatana, S. santolinifolia, and S. eremophila were the most active radical scavengers with higher total phenol contents while, S. limbata, S. xanthocheila and S. aegyptiaca were the weakest ones. The methanol extracts of S. santolinifolia, S. eremophila, S. sclarea and S. limbata inhibited the growth of all tested bacterial strains

In vitro and in vivo potential of RH strain of toxoplasma gondii [type I] in tissue cyst forming

Based on recent studies, there are controversial reports on the capacity of tissue cyst forming of Toxoplasma gondii RH strain. In this study, the capacity was evaluated by in vivo and in vitro experiments. RH strain was subcutaneously inoculated to ten Wistar rats. After one month, their blood, brain, tongue and diaphragm were collected and evaluated by MAT, PCR, pathological and bioassay methods. The parasite was cultivated in the cell monolayer. To change to bradyzoite, the media pH was altered to 6.8. Biological aspect of the bradyzoites was evaluated by incubation in acidic pepsin and it's inoculation in ten BALB/c mice. All rats showed antibodies to Toxoplasma at titers >/= 1:320 but no DNA and tissue cyst were detected in the tissues. Following intraperitoneal inoculation of rats' brain homogenate into BALB/c mice, no infection was established in none of the animals. During presence of cell culture, in acid media for a 3-5 days period, cyst-like structures were noticed when they were stained with PAS. The visible bradyzoites in the cysts that were incubated in acid pepsin medium were not able to kill any mice. This study confirmed that Iranian RH strain has lost the potential of tissue cyst forming in rats and bradyzoites cultivated in cell culture lost their resistance to acidic condition, so this strain can be a candidate for future vaccine researches

Biological activity and chemical constituents of red and brown algae from the Persian Gulf

Different solvent extracts of a red algae, Hypnea flagelliformis,and two brown algae, Cystoseira myrica and Sargassum boveanum, collected from the Persian Gulf coast were subjected to different bioassays including: 1,1-diphenyl-2-picrylhydrazyl [DPPH] free radical scavenging assay, antibacterial and antifungal activity by thin layer chromatography [TLC]-bioautography, agar disc diffusion [ADD] and nutrient-broth micro-dilution [NBMD] bioassays. The water extracts were found to have the most antioxidant activity.The antibacterial minimum inhibitory concentrations [MIC] of the active extracts were determined for the susceptible organisms, Staphylococcus aurous and Bacillus subtilis, using NBMD bioassays.The active substances were identified as free fatty acids [FFA] using gas chromatography-mass spectrometry [GC-MS] and after derivatization to their methyl esters, their concentrations were measured using GC- flame ionization detection [GC-FID]. In addition to the fatty acids, fucosterol, cholesterol and 22-dehydroxychlosterol were detected as the major sterols in S. boveanum extract using GC-MS analyses

Fragment-based binding efficiency indices in bioactive molecular design: a computational approach to BACE-1 inhibitors

One of the most important targets in Alzheimer disease is Beta site amyloid precursor protein cleaving enzyme-1 [BACE-1]. It is a membrane associated protein and is one of the main enzymes responsible for amyloid beta [A beta] production. Up to now, a considerable number of peptidic and non-peptidic inhibitors of BACE-1 have been developed. Recently, small molecule BACE-1 inhibitors have attracted the attention of scientists, because peptidic inhibitors have many pharmacokinetic problems. In the present study, several small molecule BACE-1 inhibitors were extracted from Brookhaven Protein Databank [PDB] and subjected to dissection analysis to achieve constructing fragments. Atom type, hybridization, and bond order were considered for generated constitutional fragments [simplified structures]. AutoDock version 4.2 was applied to dock various chemical fragments into BACE-1 active site. The benefits of such studies have been well revealed in previous reports. On the basis of obtained binding affinities, fragment-based ligand efficiency [LE] indices were estimated. These theoretical binding efficiencies were applied to further elucidate the key structural features of BACE-1 inhibitors. Typical results of the study were elucidated and we suggested the ways these findings might be beneficial to guide rational bioactive molecular developments. Our study confirmed that the evaluation of ligand-receptor interactions in terms of ligand efficiency indices [binding energy per atom and pK[i] per MW] could be a helpful strategy in structure-based drug discovery [SBDD] strategies

Smell Identification Function in Children with Attention Deficit Hyperactivity Disorder

OBJECTIVE: Deficits in olfactory function are common features in neurodegenerative and neuropsychiatric disorders. Olfactory processing is related to dopamine metabolism and orbitofrontal cortex functioning, both known to be involved in the neurobiology of ADHD. Some investigations suggested alterations in olfactory processing (identification and detection threshold) in patients with ADHD. Despite increasing knowledge, controversy about this topic still exists regarding children with ADHD. This study was conducted to help elucidate some of this controversy. METHODS: 50 participants (8-15 years, mean=10.70+/-1.77) with ADHD were compared to 50 controls. The two groups were well matched for age, gender and Mean School Scores (MSS). We assessed odor identification and threshold through a smell test composed of two tests of identification and detection threshold. Odor detection threshold was assessed with the odorant phenyl ethyl alcohol solved in propylene glycol using a single staircase method. Odor identification was assessed with chemical essences of five common odorants. RESULTS: The mean Sensory Identification Score for children with ADHD and the control groups were 3.76 (1.06) and 4.46 (0.76), respectively (p<0.001). The mean for Sensory Threshold Score for ADHD and control group was 6.4 (3.35) and 9.75 (2.16), respectively (p<0.001). CONCLUSION: This study replicated altered olfactory performance in ADHD. Substantial olfactory deficits across the two domains of identification and detection threshold are observed in children with ADHD. These deficits do not seem to be a result of olfactory task difficulty and are not influenced by age, gender and MSS. Further studies are required to investigate whether olfactory function can be used as a biological marker for early diagnosis, treatment and prognosis of ADHD.

Composition of the volatile oil of achillea wilhelmsii C. Koch from Iran

Composition of the volatile oil of the aerial parts of Achillea wilhelmsii C. Koch [Compositae] was investigated by GLC and GC-MS. Fifty-seven components representing 98.5% composition of the essential oil were characterized. The main components of the oil were carvacrol [25.1%], linalool [11.0%], 1,8-cineol [10.3%], E-nerolidol [9.0%] and borneol [6.4%]

Synthesis and smooth muscle calcium channel antagonist effects of new derivatives of 1, 4 - dihydropyridine containing nitroimidazolyl substituent

A group of racemic 3-[[2-hydroxyethyl], [2-Methoxyethyl], [2-acetylethyl] or [2-cyanoethyl]], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-[1-methyl-5-nitro-2-imidazolyl]-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle [GPILSM] which was induced by carbacol [1.67

Synthesis and smooth muscle calcium channel antagonist effect of alkyl. aminoalkyl 1,4 - dihydro - 2,6 - dimethyl - 4 - nitro imidazole - 3,5 pyridine dicarboxylates.

The discovery that 1,4-dihydropyridine [DHP] class of calcium channel antagonist inhibits the Ca+° influx represented a major therapeutic advance in the treatment of cardiovascular diseases such as hypertension, angina pectoris and other spastic smooth muscle disorders. A novel class of calcium channel antagonist of flunarizine containing arylpiperazinyl moiety has recently been reported. It was therefore of interest to determine the effect that selected C-3 substituents contained amino alkyl and arylpiperazine, in conjunction with a C-4 1-methyl-5-nitro-2-imidazolyl substituents on calcium channel antagonist activity. The unsymmetrical analogues were prepared by a procedure reported by Meyer in which 1-methyl-5-nitro-imidazol-2-carboxaldehyde was reacted with acetoacetic esters and alkyl 3-aminocrotonate. In vitro calcium channel antagonist activities were determined by the use of high K+ contraction of guinea pig ileal longitudinal smooth muscle. All compounds exhibited comparable calcium channel antagonist activity [IC50=10[-9] to 10[-11] M] against reference drug nifedipine [IC50=2.75 +/- 0.36 x 10[-10] M]