Pharmacological activities of some triazinopyrazolothieno pyrimidine derivatives

Triazinopyrazolothieno pyrimidine derivatives 1–5 were evaluated for their anti-inflammatory, analgesic and anticancer activities and acute toxicity. Anti-inflammatory activity of the compounds was studied using the carrageenan test. All tested compounds showed analgesic activity, 3-methoxycarbonyl-4,6-dimethyl-8-[(N-methylindolyl)methyl]pyrimido [5\u27,4\u27:4,5]thieno [3\u27,2\u27-3,4]pyrazolo [5,1-c]triazine (4) showed activity comparable to that of diclofenac. Compounds 1–5 were also screened for anticancer activity on a human lung cancer cell line (A549) and a human prostate cancer cell line (DU145) using the MTT micro-cultured tetrazolium assay method. Compound 4 showed also significant anticancer activity against both cancer cell lines, comparable to that of doxorubicin. The most active compounds were tested for their acute toxicity and median lethal doses were evaluated

ANTIMICROBIAL RESISTANCE PATTERNS OF PROTEUS ISOLATES FROM CLINICAL SPECIMENS

Total of 6840 clinical samples were collected from King Fahd Hospital at Medina, Kingdom of Saudi Arabia (KSA). Clinical samples were screened for Proteus spp. It is found that Proteus spp isolates representing about 3% of all positive samples isolated from different clinical sources. Males were found to be more vulnerable than females in acquiring Proteus infections. Results showed that the greatest number of Proteus spp. isolates from clinical specimens were isolated from wound and sputum swabs specimens representing about 88% of all clinical specimens.Thirteen different antibiotics representing different families of antibiotics were tested on Proteus spp. specimens for studying its antimicrobial sensitivity pattern. Results of antimicrobial sensitivity tests revealed that imipenem (IMP) antibiotic was the most effective antibiotic against Proteus spp. with 91% of antimicrobial sensitivity. Imipenem (Imp) was followed by amikacin (AK) with 61% of antimicrobial sensitivity.Results are recommending prescribing of imipenem (IMP) antibiotic in the treatment of Proteus spp infections. It is recommended also to prescribe amikacin (AK) in the case of sensitivity to imipenem (IMP). In acute cases, Proteus infections could require use of combined antimicrobial therapy (imipenem- amikacin). Results also demonstrated that percentage of Proteus spp. infections was highest during summer season representing about 40% of infections all year along. Summer season was followed by winter season with about 32% of infections

In vitro Anti-Leishmania Activity and Safety of Newly Synthesized Thiazolo Pyrimidine Derivatives Augmented with Interleukine-12 (IL-12) in BALB/c Mice Experimentally- Infected with Cutaneous Leishmaniasis

Purpose: To synthesize a series of novel thiazolo pyrimidine derivatives and evaluate them in vitro and in vivo for their safety and anti-leishmanial activity using BALB/c mice.Methods: Substituted pyrazolopyrimidine and pyrazolopyrazole were synthesized by reacting amino group of 2-amino-4-cyano-pyrazol]naphthalino[1,2-d]thiazole with a variety of formamide or hydrazine hydrate. The synthesized compounds were characterized by nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectroscopy (MS). The purity of the compounds was determined by elemental analysis. Safety and anti-leishmanial activity of the compounds were determined in vitro by i) viability assessment of leishmania-infected macrophages, relative abundance of IL-12p40 mRNA gene expression and levels of IL10 /IL-12 determination in supernatants of cultured macrophages treated with 2.5 and 10 μM of the compounds, using microscope cell counting, reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. ii) cytotoxicity of the compounds evaluated by determination the safety index as IC50 of the compound in macrophages/IC50 of the compound in amastigotes. iii) bioassay at 16 weeks post-infection of mice treated with the reference drug, the tested compound alone and both the compound with IL-12. Disease progression and footpad thickness were evaluated regularly during treatment.Results: Compound 4 emerged as the most active anti-protozoal compound of the series against Leishmania viability (activity 60 %) compared with the reference drug (activity 65 %). When it was combined with IL-12, the activity reached 90 %.Conclusion: Compound 4 can serve as a lead molecule for further development to a clinically useful novel class of agents.Keywords: Thiazolopyrimidine, Synthesis, Leishmaniasis, Mice, Immunotherap

Efecto de la germinación sobre la composición química y la actividad antioxidante de aceites de linaza (Linum usitatissimum L).

The present study was carried out to determine the changes in proximate composition and physicochemical characteristics of flaxseed during germination. Flaxseed was germinated for 4 days and observations were taken every day throughout the study. Changes in the seed reserve and antioxidant activity were determined during germination. The oil content of the cultivar decreased from 35.10 to 27.22%. During the germination period, the total protein content increased to 23.84%. Germinated flaxseed showed significantly higher unsaturated as compared to saturated fatty acid ratios and higher calculated oxidizability (Cox) values. The Saponification value ranged from 182 to 192 mg KOH·g–1 oil during germination. The highest peroxide value (2.4 mequiv O2·kg−1 oil) was observed at the end of germination. The unsaponifiable contents ranged from 1.62 to 1.18%. The oxidation value of the oil samples were statistically in the same range (4.1–6.4%). After 4 days of germination, oil stability was reduced to 1.0 h. The increase in ascorbic acid content was steady. Total phenolic acid contents differed significantly. The greatest concentration was detected in non germinated flaxseed oil. Germinated Flaxssed oil showed an important free radical scavenging activity towards 1-1-diphenyl-2-picrylhydrazyl (DPPH) free radicals.El presente estudio se llevó a cabo para determinar los cambios en la composición y características físico-químicas de aceites de linaza durante la germinación. La linaza se germinó durante 4 días y el estudio se realizó todos los días durante este proceso. Se determinaron los cambios en la reserva de las semilla y la actividad antioxidante. El contenido de aceite de los cultivos disminuyó de 35,10 a 27,22%. Durante este periodo, el contenido de proteína total aumentó a 23,84%. La linaza germinada mostró valores significativamente más altos de la relación de ácidos grasos insaturados frente a saturados y mayor facilidad de oxidación (Cox). El índice de saponificación varió desde 182 hasta 192 mg KOH·g−1 de aceite durante la germinación. El índice de peróxido más alto (2,4 mequiv O2·kg−1 de aceite) se observó al final de la germinación. El contenido de materia insaponificable varió desde 1,62 hasta 1,18%. La oxidación de las muestras de aceite fueron estadísticamente del mismo rango (4.1 a 6.4%). Después de 4 días de germinación, la estabilidad del aceite se redujo a 1,0 h. El aumento en contenido de ácido ascórbico fue estable. Los contenidos totales de ácidos fenólicos diferían significativamente. La mayor concentración se detectó en el aceite de linaza no germinado. El aceite de linaza germinado mostró una importante actividad de eliminación de radicales libres hacia 1-1-difenil-2-picrilhidrazil (DPPH)

Crocin mitigates carbon tetrachloride-induced liver toxicity in rats

AbstractObjectivesCarbon tetrachloride (CCl4) is one of the most dangerous hepatotoxic environmental pollutants thus this study aimed at investigating the potential preventive effect and mechanism of crocin against CCl4-induced hepatotoxicity.MethodsForty Male rats were allocated for two weeks treatment with; corn oil, CCl4 in corn oil, crocin (100mg/kg), or crocin plus CCl4. At time of euthanasia liver was removed, weighted and processed for histopathological evaluation and estimation of liver contents of active caspase3, lipid peroxidation (MDA) and reduced glutathione (GSH). We also evaluated antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)], phase I metabolizing enzyme [cytochrome P450 sub family 2E1 (CYP2E1)] an Phase II metabolizing enzyme, [glutathione-S-transferase (GST)] in liver tissue. Blood samples were used for evaluation of liver function tests and inflammatory cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)].ResultsCCl4 induced significant (p < 0.001), increase in: relative liver weight to body weight, liver MDA content, liver active caspase-3 and plasma levels of IL-6 and TNF-α. In addition, CCl4 disturbed liver histology, liver metabolizing enzymes (CYP2E1 and GST), and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase). CCl4 induced significant decrease in activities of SOD, CAT, GSH-Px and GSH content. Administration of crocin with CCl4 mitigated all CCl4-disturbed parameters and preserved liver histology close to normal.ConclusionCrocin ameliorated CCl4-induced liver injury via inhibition of inflammatory cytokines, caspase3 and oxidative stress along with modulation of liver metabolizing enzymes favoring elimination of CCl4 toxic metabolite

Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives

A series of substituted pyrazole, triazole and thiazole derivatives (2–13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported

Therapeutic Efficacy Evaluation of Metronidazole and Some Antifungal Agents with Meglumine Antimoniate on Visceral Leishmaniasis by Real-Time Light-Cycler (LC) PCR in BALB/c Mice

Purpose: To develop a highly accurate molecular assay for evaluating the efficacy of metronidazole and some antifungal agents with meglumine antimoniate against L. infantum visceral leishmaniasis in different mouse tissues. Methods: The assay was performed with the Light-Cycler system using SYBR Green I and primers amplifying ca. 120-bp fragment from minicircles of the kinetoplast DNA (kDNA).The mice were divided into two groups. Group I served to evaluate drug activity and parasite load while Group II was assigned to identify possible synergistic activity between meglumine (which is highly effective in the liver but less effective in the spleen) and drugs with significant activity against spleen infection. Results: The assay was able to detect as little as 100 fragments of L. major DNA per reaction, which is equivalent to 0.1 parasites. The standard curve designed for quantitation of parasites showed linearity over at least 6-log DNA concentration range, corresponding to 0.1 to 104 parasites per reaction with a correlation coefficient of 0.979. Metronidazole, ketoconazole, fluconazole, itraconazole and terbinafine were less effective than antimonial agents in reducing hepatic parasite load while ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection (L. infantum visceral leishmaniasis). Conclusion: The assay technique is accurate, sensitive, and rapid for the detection of kDNA and would be of great help to scientists who use animals to monitor the efficacy of anti-leishmanial drugs or vaccines