Trends in Pharmaceutical Sciences
Volume:1 Issue: 3, Sep 2015

Coenzyme Q10 (CoQ10) is a vitamin-like substance, and a natural intermediate of electron transport chain (ETC) of mitochondria which can accepts and donates electrons from complex I to complex II. CoQ10 shares a biosynthetic pathway with cholesterol, therefore it can be a potential target of the widely available lipid-lowering agents. The lipid lowering drugs such as statins, are widely administered to individuals who have high cholesterol levels and potential risk for cardiovascular diseases. Statins do not cause serious adverse effects in human however its long-term administration can cause a variety of myopatic complaints.This article reviews the a) clinical benefits of CoQ10 b) association between administration of statin and CoQ10 deficiency and c) involvement of CoQ10 in statin-associated myopathy.

Nephrotoxicity is generally considered as the most clinically significant and dose-limiting adverse reaction of amphotericin B. Currently, only the clinical effectiveness of salt loading and administering lipid formulations of amphotericin B have been clearly demonstrated to prevent its nephrotoxicity. In this review, we collected the published data related to dopamine receptor agonists in preventing amphotericin B nephrotoxicity. A literature search was conducted by the relevant keywords like ‘‘amphotericin B”, “nephrotoxicity’’, and ‘‘dopamine’’ in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. Four relevant articles were considered. Results of all the 3 experimental studies demonstrated that co-administration of dopamine (0.5-10 μg/kg/min) as continuous intravenous infusion, SK&F R-105058 (10 mg/kg twice daily), a prodrug of fenoldopam, orally, or fenoldopam, a relatively selective dopamine receptor type 1 agonist, (0.5 or 1 μg/kg/min) as continuous intravenous infusion can at least significantly mitigate the decrease in creatinine clearance caused by amphotericin B. Furthermore, fenoldopam and SK&F R-105058 can also protect against or delay amphotericin B-induced tubular damages. In contrast, the only clinical trial published until now found that simultaneous continuous intravenous infusion of low dose dopamine (3 μg/kg/min) had no beneficial effects on the incidence, severity, as well as time onset of developing amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Considering the lack of beneficial effects in different settings such as acute kidney injury of any cause, negative results of the only clinical trial, and risk of significant adverse reactions, continuous intravenous infusion of low dose dopamine (1-3 μg/kg/min) or selective dopamine receptor type 1 agonists (e.g., fenoldopam) currently appears to have no real clinical role in preventing or attenuating amphotericin B nephrotoxicity.

Eremostachys laciniata, having rich flavonoids content, is expected to have a considerable antioxidant effects. We used ACMS (Accelerated cytotoxic or protective mechanism screening technique) to evaluate possible antioxidant effect of E. laciniata rhizome against oxidative cell damages induced by different types of oxidative stress such as iron-8-hydroxyquinolin (IQ) complex and copper in freshly isolated liver cells. The extracts were prepared with n-hexane, dichloromethane and methanol. Hepatocytes were isolated from male Sprague-Dawley rats by a two-step collagenase perfusion. Cell viability was measured by trypan blue exclusion method. DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay was used to evaluate the antioxidant activity. ROS formation was measured by using DCFDA (2, 7-dichlorofluorescin diacetate) probe, mitochondrial membrane potential (MMP) was assessed by rhodamine 123 fluorescence and lipid peroxidation was determined by thiobarbituric acid reactive substances (TBARS) assay. The MET extract was demonstrated to possess a significant radical scavenging activity (RC50%=0.212). Unlike MET extract, the n-hexane and dichloromethane extracts showed toxic effects in cell suspensions. The MET extract significantly decreased cell death and ROS formation induced by IQ complex and copper and demonstrated protective effects against copper-induced mitochondrial membrane potential collapse and lipid peroxidation. The protection induced by MET extract can be attributed to antioxidant characteristics of phenylethanoids content.

Giardiasis is a protozoal infection of small intestine caused by giardia lamblia. The disease is usually asymptomatic though it can present as acute or chronic diarrhea. Giardiasis is a major cause of intestinal infection and Iran is an endemic area of the disease. Despite reports about drug resistance, long course treatment and various side effects, metronidazole is the drug of choice for giardiasis.In this study we investigated in vivo effects of five new derivatives (a-e) of metronidazole (MTZ) on the giardia lamblia trophozoite in infected mice. Giardia intestinalis cysts were isolated from a patient and purified by sucrose gradient method. Fifty Purified cysts were inoculated to mice and after development of infection, the new metronidazole derivatives were given to the mice and results were compared to metronidazole as positive control.Compounds a and b showed desirable antigiardiasis activity and could destroy the cyst and trophozoite of giardia lamblia in mice after both two and four days, but the activity of the other compounds appeared only after 4 days.

Myrtus communis L. is a plant traditionally used as an antiseptic and disinfectant drug. In this research, the antioxidant activity of Myrtus communis was assayed by evaluating radical scavenging activity, reducing power, FRAP method and determination of phenolic compounds. The methanolic extract of leaves of Myrtus communis was fractionated by using petroleum ether, chloroform, ethyl acetate and buthanol. In reducing power, different concentrations of samples were mixed with phosphate buffer, ferrocyanate, TCA and ferric chloride. Different concentrations of samples were mixed with DPPH and after 30 min the absorbances were measured. For determination of phenolic content, 500 µl of sample was mixed with Folin-Ciocalteu and sodium carbonate. For determination of flavonoids, 500 µl of sample was mixed with 2 ml of distilled water, NaNO2 and NaOH. In reducing power method, chloroform fraction showed the highest reducing capacity. In the DPPH radical scavenging method, the highest antioxidant capacity was found in buthanol fraction (IC50=84.42±1.8 µg/ml). In FRAP method, the highest antioxidant capacity was found in crude extract (5.4±0.3 mg/ml) and buthanol fractions (5.51±0.4 mg/ml), respectively. The highest amount of phenolic compounds was detected in ethyl acetate fraction of Myrtus communis (17.5±0.001 µg/g). The highest amount of flavonoids was found in crude extract of Myrtus communis (171.9±7.3 µg/ml). Overall, we can suggest that the leaves of Myrtus communis can be used as antioxidant and as a food additives to avoid oxidative degradation of foods.

A simple and rapid chromatography method was developed for determination of lamotrigine in human plasma. The method was used to compare the pharmacokinetic (PK) parameters of 50 mg generic and the reference lamotrigine (Lamictal) tablets in healthy Iranian volunteers. High performance liquid chromatography - ultraviolet method was developed and validated to determine lamotrigine concentration in plasma samples. The method was linear over the range of 0.1 to 15 µg/ml. The accuracy and precision were within the acceptable range. Limits of detection and quantification were calculated 0.06 and 0.10 µg/mL, respectively. A randomized, single-dose, two-period, two-sequence crossover study was carried out in healthy subjects receiving either the test or the reference products in each period. Pharmacokinetic parameters were determined by non-compartmental PK model. Bioequivalency between the generic and the reference product was investigated according to the guidance for industry issued by US Food Drug Administration. AUC0-t, AUC0-∞ and Cmax were calculated for the generic product 12.50±2.76 µg.h/mL, 15.04±3.66 µg.h/mL and 0.38±0.08 µg/mL, respectively. The 90% confidence interval for the test/reference ratios were laid in the range of 0.80-1.25 for the log-transformed PK parameters. The generic product is bioequivalent and can be prescribed by practitioners while indicated, however the AUC and Cmax were lower in Iranian population if compared to the literature, which requires further investigations.

Klebsiella pneumoniae is a hospital-acquired pathogen that leads to various infections. Hence, efforts to develop an effective vaccine against that pathogen are well documented. Our interest is the production of the previously designed multi-epitope vaccine construct against the K. pneumoniae in a prokaryotic host. Therefore, a new construct containing the nucleotide sequence of the novel vaccine was successfully expressed in Escherichia coli and then purified by Ni-NTA spin column. The purified recombinant protein can be considered as potential vaccine candidate for wet-laboratory analysis aiming to fight K pneumoniae .

4-Anilinoquinazolines have been widely studied as anticancer agents. Despite the widespread utility of this class of compounds, the reported syntheses of 4-anilinoquinazolines require multistep and low-yielding pathways. A novel strategy to prepare 4-anilinoquinazoline derivatives based on the cyclization of anthranilic acid is described. By using of dichloro anthranilic acid we could etherified the quinazoline ring in order to mimic the erlotinib structure as a tyrosine kinase inhibitor. Our new compounds contain different substitutions at the meta-positions of the quinazoline ring instead of the ortho-positions of erlotinib. We synthesized ten new 4-anilinoquinazoline derivatives (17-26) in only 4 steps with desirable yields.