PHARMACEUTICAL SCIENCES
Year:2013 | Volume:19 | Issue:1|Papers Count:5

Background: Scrophularia oxysepala Boiss. is endemic to western and central regions of Iran, and belongs to the genus Scrophularia (family: Scrophulariaceae), which has long been used in traditional medicines. In the present work, chemical composition of the essential oil of the aerial parts of this species was analyzed.Methods: The air-dried ground aerial parts of S. oxysepala were subjected to hydro-distillation. The resulting oil was analyzed, for the first time, by the gas chromatography/mass spectrometry (GC-MS) and gas chromatography/flame ionization detection (GC-FID). Free-radical-scavenging activity of the essential oil was determined by the DPPH assay. Adults of Oryzeaphilus mercator were used for contact toxicity insecticidal assay.Results: A total yield of 0.1 ml of essential oil per 100 g of plant dry mass was obtained, and 15 compounds were identified, representing 91.2% of total oil. The essential oil was characterized by a high content of aromatic compounds and phytol. The main constituents were phytol (25.3%), methyl benzyl alcohol (9.3%), dehydrodieugenol (6.7%), methyl benzaldehyde (5.3%) and eugenol (1.3%). The low level of free-radical-scavenging activity of the essential oil was demonstrated by the RC50 value of 1.852mg/ml, and the insecticidal activity was also found to be low.Conclusion: The insecticidal activity of this essential oil was not remarkable, but was time and concentration-dependent. The low free-radical-scavenging activity was probably due to its low percentage of phenolic compounds.

Background: The renin angiotensin system which is stimulated by angiotensin II, leads to increase in blood pressure. An angiotensin II receptor antagonist can control effectively hypertension. Synthesis of new compounds that have the key structural elements present in angiotensin receptor antagonists is of interest. Herein, we report the synthesis of novel Alkyl 2-azido-3- [1- [[2' - (tetrazol-5-yl) biphenyl-4-yl] methyl] -2-alkylimidazolyl] acrylate (4 and 6).Methods: 2-Alkyl-4 (5) -hydroxymethylimidazoles were synthesized via Weidenhagen reaction using copper salt, an aldehyde, dihydroxyacetone and concentrated ammonium hydroxide.2-Alkyl-4 (5) -hydroxymethylimidazoles were oxidized by heating with MnO2 in CH2Cl2: dioxane to its carboxaldehyde derivatives. The carboxaldehyde derivatives were reacted with tritylated [4´- (bromomethyl) biphenyl-2-yl] tetrazole in presence of potassium carbonate to give two regioisomers 1 & 2 that separated by column chromatography. The regioisomers 1 & 2 were employed in the synthesis of 2-azidoacrylate derivatives 3 & 5 using sodium alkoxide and alkyl α-azidoacetate. Consequently, the protecting group of tetrazole was removed by stirring the compound 3 and 5 in 10% hydrochloric acid solution at room temperature.Results: The regioisomers 1 & 2 were separated chromatographically in 1: 3 proportions using 70: 30 toluene: ethyl acetate as eluent, respectively. The alkyl 3-substituted imidazol-2-azido acrylate derivatives were synthetized as oily form in 19-25% yield. The deprotection of tetrazole was afforded light yellow oily final compounds in 60-65% yield.Conclusion: Four new alkyl α-azidoacrylate derivatives bearing biphenyl tetrazole moiety were synthetized via Knoevenagel condensation. The protecting group was removed in acidic media to afford final compounds 4 and 6. The chemical structures of synthesized compounds were characterized by FT-IR and HNMR spectroscopies.

Background: It is well known that progesterone (i.p.) have a potent anticonvulsant effect in human and animal. This study was designed to evaluate the involvement of opioid receptors in this effect of progesterone in ovariectomized mice.Methods: All animal received intraperitoneal injection of drugs (progesterone and naloxone) two week s after surgery, for ovariectomy. Convulsion induced by subcutaneous injection of drugs. Onset, Number, death time and duration of convulsion were recorded for evaluation of the convulsion.Results: Progesterone (25, 50 mg/kg i.p.) decreased the convulsive symptoms. Anticonvulsant effect of high dose of progesterone was abolished by naloxone (5 mg/kg i.p.). Administration of the same doses of the naloxone, did not alone affect strychnine- induced convulsion.Conclusion: These results suggest that central opioids receptors may be play an important role in the anticonvulsant effect of progesterone.

Background: Angiogenesis is the process in which the new blood vessels are formed from pre-existing ones. The development of the vascular system is one of the earliest events in organogenesis. Since angiogenesis is a key process in the promotion of cancer and its metastasis (most common cause of cancer death in human), inhibition of angiogenesis is one of the promising approaches for treatment of tumor growth and metastasis. In this study, several derivatives of 4-aryl-4H-chromenes bearing methoxy substituent have been synthesized with boric acid as catalyst and investigated with potential anti-angiogenesis effects as well as anti-angiogenic mechanism.Methods: Anti-angiogenic and anti-proliferative effects of the prepared compounds checked on three-dimensional culture of human umbilical vein endothelial cells (HUVECs) in collagen matrix and HUVEC proliferation assay as well as matrix metalloproteinase (MMP) gelatinase assay in the endothelial cell-based experimental system. Finally, anti-angiogenic mechanism of the compounds was identified, using gel zymography method.Results: Among the synthesized compounds 4a and 4h were as the most active in these series. The compound 4a was caused angiogenesis inhibition with complete suppression at 3 mg/ml (8.537 mM) and 4h at 1.6 mg/ml (4.196 mM).Conclusion: At end, chromene derivatives can serve as the lead molecules for further development of a new class of anti-angiogenesis agents.

Background: Pseudomonas (P.) aeruginosa exotoxin A (PE) is one of the most potent bacterial toxins ever been identified. It catalyzes ADP-ribosylation of cellular elongation factor 2 and specifically arrests protein synthesis leads to cell death. Different derivatives of PE have been used for construction of immunotoxins against cancers. The aim of this study was to clone and express a DNA fragment of PE encoding a truncated exotoxin lacking the cell binding domain of native exotoxin.Methods: The genomic DNA extracted from P. aeruginosa PAO1 was used in a polymerase chain reaction (PCR) containing the primers for amplification of domains 2-3 of PE gene. The PCR product was then cloned into the pET-22b vector and transformed into E. coli BL21 cells for expression. The His-tagged recombinant PE38 was purified by Nickel affinity chromatography and characterized.Results: Sequencing of the cloned fragment confirmed the identity of gene as PE domains 2-3. Analyzing the recombinant protein expression by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed high level expression of recombinant protein. Results of western blotting with anti native-exotoxin A showed proper conformational structure of purified recombinant protein.Conclusion: The results of this study indicated that the presented expression system is an efficient system for the production of recombinant truncated exotoxin A. This recombinant protein can be used for the construction of toxin conjugates against different cancers.