Anticandidal, antibacterial, cytotoxic and antioxidant activities of Calendula arvensis flowers.

Calendula arvensis (CA) is one of the important plants used in traditional medicine in Morocco, due to its interesting chemical composition. The present study aimed to determine the anticandidal, antioxidant and antibacterial activities, and the effects of extracts of CA flowers on the growth of myeloid cancer cells. Also, to characterize the chemical composition of the plant. Flowers of CA were collected based on ethnopharmacological information from the villages around the region Rabat-Khemisset, Moroccco. The hexane and methanol extracts were obtained by soxhlet extraction, while aqueous extracts was obtained by maceration in cold water. CA extracts were assessed for antioxidant activity using four different methods (DPPH, FRAP, TEAC, ß-carotene bleaching test). Furthermore, the phenolic and flavonoid contents were measured, also the antimicrobial activity has been evaluated by the well diffusion method using several bacterial and fungal strains. Finally, extracts cytotoxicity was assessed using MTT test. Phytochemical quantification of the methanolic and aqueous extracts revealed that they were rich with flavonoid and phenolic content and were found to possess considerable antioxidant activities. MIC values of methanolic extracts were 12.5-25µg/mL. While MIC values of hexanolic extracts were between 6.25-12.5µg/mL and were bacteriostatic for all bacteria while methanolic and aqueous extracts were bactericidal. In addition, the extracts exhibited no activity on Candida species except the methanolic extract, which showed antifungal activity onCandida tropicalis 1 and Candida famata 1. The methanolic and aqueous extracts also exhibited antimyeloid cancer activity (IC50 of 31µg/mL). In our study, we conclude that the methanolic and aqueous extracts were a promising source of antioxidant, antimicrobial and cytotoxic agents.

Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties.

Comparative plasma disposition kinetics of albendazole and its new benzimidazol prodrug in dog.

The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug [1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl] (ABZBoc), following their oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0->∞), and analyzed using the Student's t-test, P<0.05. Thus,the pharmacokinetic analysis indicated four statistically significant changes in the pharmacokinetic parameters defined above of the albendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs.

[Anti-inflammatory activity of aqueous and ethanolic extracts of Zygophyllum gaetulum]. / Activité anti-inflammatoire des extraits aqueux et éthanolique de Zygophyllum gaetulum.

Zygophylle or Zygophyllum gaetulum Emberger and. Maire is a Moroccan medicinal plant which has been used as an anti-inflammatory, antidiabetic, antispasmodic and antidiarrheic. The present study was carried out to study and compare the anti-inflammatory effect of ethanolic extract with aqueous extract of Z. gaetulum. Organic extract of Z. gaetulum was obtained in soxhlet apparatus. Aqueous extract was obtained by infusion. The Wistar albinos rats of either sex weighing 200-300 g aged 2-3 months were used for this experiment. The rats were housed under standard environmental conditions. The anti-inflammatory activity was estimated by measuring the oedema induced by carragenin according to the method of Winter and al. Ethanolic extract of Z. gaetulum reduced the increase of the paw volume with a percentage of inhibition of 46% (p<0.01), this percentage was 47.48% (p<0.01) with aqueous extract. The inhibition decrease in time, it arrived to 39% (p<0.01) at the sixth hour while the activity of aqueous extract decrease a lot. In conclusion, Z. gaetulum is an interesting plant which the aqueous and éthanolic extracts could be used scientifically in the treatment of inflammation.

[Pharmaceutical analysis of antibiotic drug prescription in the burns and plastic surgery departiment of the Mohammed Military Teaching Hospital]. / Analyse Pharmaceutique de la prescription des antibiotiques au service des brules et chirurgie plastique de l'Hopital Militaire d'Instruction Mohammed V, Maroc.

Infection has long been the main cause of mortality in severely burned patients. The aim of this work is to assess the prescription of antibiotics in our Burns and Plastic Surgery Department in relation to the recommendations of the manufacturers. A summary is provided of the specific features of these products. Patients hospitalized in the Mohammed V Military Teaching Hospital, Rabat, Morocco, during the period January 2008/May 2009 and treated with antibiotics were considered. This retrospective study concerned 227 nominal medical prescriptions of antibiotics to 41 patients: 70% of the prescriptions were nondocumented. The commonest method of administration was by injection (89%). Various groups of therapeutic drugs were used: betalactamines (65%), glycopeptides (10.5%), aminosides (9%), quinolones (7%), and colistin (4.3%), plus 4.2% from other groups (metronidazole 500 mg, perfusion; fluconazol 100 mg/50 ml, injection; rifampicin 600 mg, perfusion; silver sulphadiazine, 2% fusidic acid cream). A total of 227 nominal medical prescriptions were analysed: the dosages and counter-indications were correctly respected. Three drug interactions were recorded (fluconazol-rifampicin, fluconazol-Saccharomyces boulardii, amikacin-vancomycin). This study shows the importance of the pharmaceutical analysis of prescriptions for antibiotics used in a burns unit, which are active but therefore very toxic.

[Synthesis, chemical and toxicological study of a new benzimidazol derivative]. / Synthèse, étude chimique et toxicologique d'un nouveau dérivé benzimidazole.

Hydatidosis is a cosmopolitan parasitic disease that remains a real public health problem in highly endemic countries. Surgery is the mainstay treatment, but with significant morbidity and mortality. In addition, contraindications for surgery emphasize the importance of developing effective medications. Currently, albendazole is the main anti-hydatid agent used worldwide. It has proven efficacy but limited bioavailability due to weak absorption. In order to improve the bioavailability of this molecule we synthesized an ester of albendazole, which exhibits a totally modified solubility compared with the princeps compound. This synthesis was achieved with an output of 75%. The structure of the synthetic product was established by IR spectrometry and by proton nuclear magnetic resonance. A careful toxicity study revealed that this product has little toxicity when administered intraperitoneally and orally in mice, with a lethal dose 50 of 2,500 mg/kg per os and 2,250 mg/kg intraperitoneally, values comparable to those of albendazole. This in vitro parasitological study demonstrated that the chemical changes introduced on the albendazole molecule had no effect on its antiparasitic activity.

Synthesis of new N-substituted pyrrolidin-2-ones as cyclic analog of gamma-aminobutyric acid.

Some new N-substituted pyrrolidin-2-ones, cyclic analogs of baclofen and of 3-(5-methylbenzo[b]furan-2-yl)-gamma-aminobutyric acid, have been prepared starting from corresponding pyrrolidinones and characterized.

Waste water bacterial isolates resistant to heavy metals and antibiotics.

Sewage water of Casablanca, an industrial city in Morocco, was studied for microorganisms resistant to heavy metals. Isolates were purified and collected on agar slants to be screened for resistance to heavy metals, including mercury in vitro. The strains that showed high resistance to heavy metals were also studied for their resistance to antibiotics and aromatic hydrocarbons. Results indicated that the strains most resistant to all tested products belonged to Ps. fluorescens, Ps. aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus sp. These strains exhibit high minimal inhibitory concentrations for heavy metals such as cadmium (2 mm) or mercury (1.2 mm). Growth of Ps. fluorescens and Klebsiella pneumoniae in the presence of heavy metals was also determined, and the growth curves indicated that mercury, copper, and zinc present a slight inhibitory action, while cadmium and silver could have a potent inhibitory action on growth compared with the controls. These studies also investigated growth in media containing aromatic compounds as the sole source of carbon. The results demonstrate that these strains could be good candidates for remediation of some heavy metals and aromatic compounds in heavily polluted sites.

[Use of iodized salt and the risk of iodine overload]. / Utilisation du sel iodé et risque de surcharge en iode.

Iodine-deficiency disorders are a major problem of public health in Morocco. To mitigate this deficiency, the iodination of all the salt intended for human consumption in a proportion of 80 +/- 10 mg/kg of salt has become obligatory since a decree published in 1995. We estimated that this rate of iodized salt issued risked inducing an iodine excess in the population. To check this hypothesis, we provided 7 families made up of 28 subjects, who at the start were consuming a non-iodized salt, with the decreed, iodized salt and we followed the evolution of their urinary iodine excretion over a period of 3 weeks. The mean values of urinary iodine excretion of the 28 subjects were 12.8 micrograms/dl before use of iodized salt and 26.8, 35.5 and 63.2 micrograms/dl, respectively, after 7, 14 and 21 days from the introduction of iodized salt into their diet. After 21 days of the use of iodized salt, 84.6 per cent of the subjects had an iodine excess. We conclude that prolonged use of this iodized salt exposes the population to the risk of thyroid disorders.

Isomers of substituted 3-benzo[b]furyl and 3-thienylaminobutyric acids as potent ligands of the GABA-B receptor: synthesis and preparative liquid chromatographic separation.

Baclofen (4-amino-3-(4-chlorophenyl)butyric acid) is the only selective agonist for GABA-B receptors. Its R-(-)-enantiomer is about 100 times more active than the S-(+)-enantiomer. In the search for new compounds that bind to GABA-B receptors, it is very important to clarify the structural requirements. The authors report the synthesis and separation of isomers of various 3-heteroaromatic (benzo[b]furan and thiophen) aminobutyric acids. The 4-amino-3-(7-methylbenzo[b]furan-2-yl)butanoic acid is a potent and specific ligand for GABA-B receptors, with an IC50 value of 5.4 microM for the displacement of [3H] GABA.

Chemical structure and hemodynamic effects of two new pyridazinone derivatives.

Two new pyridazinone derivatives were selected among two series and assayed for their hemodynamic effects. Their synthesis is described and their chemical structure confirmed by I.R. and N.M.R. data. The 5-arylhydroxymethyl-3-pyridazinone did not induce any significant hemodynamic changes. However, the 5-dichlorobenzylidene-3-pyridazinone, intravenously injected, was active in anesthetized dogs. Moderate doses induced modifications in the heart rate, left ventricular dP/dt max and femoral blood flow and resistance.