Ispitivanje antidepresivnog, sedativnog i analgetskog djelovanja novih fuzioniranih derivata tiofena

This study was aimed at the synthesis of fused benzothiophene derivatives containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea derivatives 2a,b. Cyclization of the latter products gave the annulated benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a series of heterocyclization reactions through the reaction with some chemical reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also, this work was extended to study the potential role of the novel synthesized thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg1 body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in the forced-swimming test. No compound showed sedative effect. Visceral pain evoked by i.p. injection of acetic acid in mice was significantly inhibited by all compounds at a high doses.U radu je opisana sinteza fuzioniranih derivata benzotiofena koji sadrže heterociklički ostatak bitan za farmakološko djelovanje. Tiourea derivati 2a,b dobiveni su reakcijom derivata tetrahidrobenzo[b]tiofena 1a,b s etoksikarbonilizotiocijanatom. Iz njih su dalje priređeni anulirani derivati benzo[b]tienopirimidina 3a,b. Spojevi 2a,b i 3a prevedeni su reakcijama heterociklizacije u benzo[b]tienopirimidine 5a,b-8a-c. Ispitivano je antidepresivno, sedativno i analgetsko djelovanje novosintetiziranih derivata tiouree 2a i benzo[b]tienopirimidina 3a, 5b, 6a i 8b u dvije doze (15 ili 30 mg kg1 tjelesne mase). Spojevi 2a, 3a i 5b pokazali su blago antidepresivno djelovanje u testu forsiranog plivanja, dok sedativni učinak nije pokazao niti jedan ispitivani spoj. Visceralna bol inducirana i.p. injekcijom octene kiseline u miševa značajno je inhibirana sa svim spojevima, ali u visokim dozama

Synthesis and Biological Evaluation of Some Pyridine Derivatives as Antimicrobial Agents

In this study, several pyridine derivatives were synthesized and evaluated for their in vitro antimicrobial activity against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Aspergillus niger and Candida albicans). The intermediate chalcone derivatives 2a,b were synthesized by condensation of pyrazole aldehydes 1a,b with acetophenone in alcoholic KOH. Cylization of 2a,b with ethyl cyanoacetate and ammonium acetate resulted in pyridine carbonitrile derivatives 3a,b. Furthermore, condensation of pyridine-4-carboxaldeyde, 4 with different amino-derivatives gave rise to pyridine derivatives 5a,b, 6a,b. The oxadiazole derivative 7a was prepared by cylization of 6a with acetic anhydride. Characterization of the synthesized compound was performed using IR, 1H NMR, 13C NMR spectra and elemental microanalyses. The antimicrobial test results revealed that compounds 5a, 6b and 7a (MIC = 50 μg/ml) exhibited half fold antibacterial activity compared to ampicillin (MIC = 25 μg/ml), against B. cereus. On the other hand, compound 3b (MIC = 25 μg/ml) showed an equivalent activity compared to miconazole (MIC = 25 μg/ml) against C. albicans and to clotrimazole (MIC = 100 μg/ml) against the clinical isolate C. albicans 6647. Moreover, this compound was further tested for its acute toxicity profile. The results showed that its oral and parentral LD50s are more than 300 mg/kg and 100 mg/kg, respectively. Therefore, compound 3b is a good candidate as antifungal agent with good acute toxicity profile, and deserves more investigation to find out its mechanism of action and bioavailability.Keywords: synthesis, pyridine derivatives, in vitro antibacterial, antifungal, acute toxicit

Short Communication: Comparative Quality Evaluation of Some Brands of Paracetamol Tablets, Suppositories and Syrups

The present study assesses the quality and the physicochemical properties of paracetamol dosage forms (tablet, suppository and syrup samples) from different drug outlets in Addis Ababa. Identity, weight uniformity, disintegration and dissolution times, assay for active ingredient content and pH test (for syrup) were performed. Hardness and drug release (t50% and t90%) of the different brands of paracetamol tablets were also evaluated and compared. The study showed that none of the tablet samples did meet the USP specification for assay of active ingredient content. One of the syrup samples (Efferalgan®) tested, contained less than the specified amount of the active principle. Keywords: quality evaluation, physicochemical properties, paracetamol dosage forms, drug outlets, Addis AbabaEthiopian Pharmaceutical Journal Vol. 26 (1) 2008: pp. 59-6

Development and Validation of an HPLC Method for the Simultaneous Analysis of Dextromethorphan HBr, Potassium Guaiacolsulfonate and Sodium Benzoate in Cough Mixture

A rapid, sensitive and selective reversed-phase high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of dextromethorphan hydrobromide (DXM), sodium benzoate (SB) and potassium guaiacolesulfonate (PGS) in cough mixture. The combined drug mixtures were separated through a Hichrom C8 (octyl), 25 cm x 4.6 mm ID, 5 μm column with a mobile phase composed of methanol and 10 mM phosphate buffer pH 3 (1:1), a flow rate 1ml/min, injection volume 10 μl and quantification by UV detection at λ max 219 nm. The method provided a short analysis time: PGS, tR = 3.07 min; SB, tR = 8.09 min and DXM, tR = 9.29 min. Validation was performed using raw materials and the pharmaceutical preparation which contains the compounds described above. The method was validated for linearity, precision and accuracy. Five factors were selected to be used in the robustness test (temperature of the column, volume of methanol in the mobile phase, pH of the aqueous phase in the mobile phase, flow rate and time of preparation) and the resolution between SB and DXM was measured for each factor. The statistical treatment (t-test with 4 degrees of freedom and at α = 0.01) did not show significant difference with regard to temperature of the column, pH of the aqueous phase in the mobile phase, flow rate and time of preparation showing that the method is robustic. With regard to percent organic modifier (methanol) a significant difference was observed indicating that care should be taken during the preparation of mobile phase proportions. Keywords: high pressure liquid chromatographic method, dextromethorphan HBr, sodium benzoate, potassium guaiacolsulfonate, cough mixtureEthiopian Pharmaceutical Journal Vol. 26 (1) 2008: pp. 39-4

Microwave Assisted Synthesis of Some New Fused 1,2,4-Triazines Bearing Thiophene Moieties With Expected Pharmacological Activity

Rapid and efficient solvent-free synthesis of 4-amino-3-mercapto-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-5(4H)-one 1 under microwave irradiation is described. Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b][1,3,4]thiadiazinones, 1,3,4-thiadiazolo[2,3-c][1,2,4]triazinone and pyrazolo[5,1-c]-[1,2,4]triazine-7-carbonitrile, have been synthesized by treatment of 1 with bifunctional oxygen and halogen compounds, CS2/KOH and malononitrile via heterocyclization reactions, in addition to some uncondensed triazines. Structures of the products have been deduced from their elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR). Select new synthesized compounds were screened as anticancer agents, with some showing activity as cytotoxic agents against different cancer cell lines