Abdullah A. Al-Badr

Chapter 4 – Flurbiprofen

Publisher Summary Racemic flurbiprofen is one of the well-known forms of nonsteroidal anti-inflammatory drug (NSAID) substances. The enantiopure (S)-enantiomer exhibits a stronger anti-inflammatory activity (30-fold higher as compared to rac-flurbiprofen); however, flurbiprofen is still currently produced in large quantities as a racemic mixture. rac-Flurbiprofen is a NSAID used in the treatment of pain or inflammation in humans. Flurbiprofen is indicated for the management of vernal keratoconjunctivitis, postoperative ocular inflammation, herpetic stromal keratitis, excimer laser photorefractive keratectomy, and ocular gingivitis. Recent reports suggest potential topical and systemic use of flurbiprofen in radioprotection, the inhibition of colon tumor, the protection of postirradiation myelosuppression, pain management after foot surgery, and peridontal surgery. It is recognized that the enantiomers of biologically active compounds usually display different physiological activities. There has also been very rapid progress in asymmetric synthetic methods in recent years. As a result, increasing attention is being paid to the synthesis of nonracemic chiral drugs. One of the major groups of anti-inflammatory agents is the arylpropanoic acid, such as flurbiprofen, where the activity resides in the (S) isomers.

Primaquine Diphosphate: Comprehensive Profile

Publisher Summary This chapter deals with primaquine diphosphate, which is an orange‐red or orange crystalline powder, odorless and has bitter taste, solution is acid to litmus. Primaquine is an 8‐ aminoquinoline antimalarial agent, which is effective as tissue schizontocide against intrahepatic forms of all types of malaria parasite and is used to produce radical cure of vivax and ovale malarias. Primaquine is also used in the treatment of Pneumocystis carinii pneumonia in AIDS patients in combinations with clindamycin. Primaquine should be administered cautiously to ill patients with any serious systemic disease characterized by a tendency to granulocytopenia, such as rheumatoid arthritis or lupus erythematosus. The X‐ray powder diffraction pattern of primaquine diphosphate is performed using a Simons XRD‐5000 diffractometer. The binding of primaquine and three other aminoquinoline antimalarial agents to native and denatured calf thymus DNA, by equilibrated dialysis and direct spectrophotometry is studied. The binding of these drugs to DNA is (1) accompanied by a decrease in absorbance of the ligand, (2) decreased by an increase in ionic strength, (3) decreased by addition of magnesium ion to a greater extent than would be expected from ionic strength effects alone, and (4) decreased under some conditions by the presence of four molar urea. Pharmacokinetics, thermal methods of analysis, and spectroscopy methods are also described in the chapter.

3,5-disubstituted thiadiazine-2-thiones: new cell-cycle inhibitors.

Two series, a and b, of 3-cyclopentyl or (3-cyclohexyl)-5-substituted-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTT) 2a–9a and 3b, 4b, 6b–9b, were synthesized to develop new cell cycle inhibitors. Variable and promising in vitro antiproliferative activities were shown with the synthesized THTT derivatives. Compound 5a with a 5-cyclopentyl group on position-3 and a glutamine residue on position-5 of the THTT moiety showed maximum activity (IC50 = 8.98 μM). Compound 5a possessed notable cell cycle disrupting and apoptotic activities with enhanced selectivity against cancer cells, suggesting the potential for the development of new selective cell cycle inhibitors. There is no evident relationship between the cytotoxic activity of the tested compounds and their lipophilicity. In addition, a pharmacophore based study was performed to explain the biological activity on structural bases. A successful model was generated with a good correlation with the observed activity.

Analytical Profile of 5-Fluorouracil

Publisher Summary This chapter discusses the analytical profile of 5-fluorouracil. 5-Fluorouracil has been used in the treatment of cancer €or more than two decades. It is a fluorinated antimetabolite of the pyrimidine uracil. It slows tumor cell growth by inhibiting thymidine formation, thereby inhibit protein synthesis by incorporating into RNA. Its trade names are adrucil, armuel, efudex, and fluril. Its molecular weight is 130.08. It is white to practically white, odorless, crystalline powder, crystals from water or methanol. Its melting point lies between 282 to 283°C with decomposition. The following thermodynamic and physicochemical parameters were predicted values based on the available heat of fusion, melting point, solubility parameters and molar volume of 5-Fluorouracil (5-FU).

Synthesis and antimicrobial activity of new furan derivatives

Abstract5-Nitrofuran derivatives were synthesized and their antibacterial activity was investigated using standard bacterial strains and clinical isolates. The compounds showed inhibitory effects on both Gram-positive and Gram-negative organisms.

Chapter 6 – Lornoxicam

A comprehensive profile on lornoxicam, the oxicam nonsteroidal anti-inflammatory agent which is used in the muscular skeletal and joint disorders such as osteoarthritis and rheumatoid arthritis, is prepared. This profile contains the following sections: description, uses and applications, methods of preparation, physical characteristics, methods of analysis, mechanism of action, pharmacokinetics, reviews, and stability. The physical characteristics section includes ionization constant, solubility, partition coefficient, thermal methods of analysis. X-ray powder diffraction pattern, crystal structure, ultraviolet spectroscopy, vibrational spectroscopy, proton and carbon-13 nuclear magnetic resonance spectrometry, and mass spectrometry. Methods of analysis section includes spectrophotometry, polarography, and chromatography (TLC, HPLC, HPLC-MS).

Chapter 2 cytarabine.

Publisher Summary This chapter describes cytarabine, its nomenclature, formulae, preparation methods, physical characteristics, analytical methods, biological analysis, pharmacokinetics, metabolism, stability, and pharmacology. Cytarabine, a pyrimidine nucleoside analog, is an antimetabolite, antineo-plastic, which inhibits the synthesis of deoxyribonucleic acid. Its actions are specific for the S-shape of the cell cycle. It also has antiviral and immunosuppressant properties. Cytarabine is mainly used in the treatment of acute leukemia, especially acute nonlymphoblastic leukemia when it is often given in association with thioguanine and an anthracycline such as doxorubicin or daunorubicin. It is also given in the blast crisis of chronic myeloid leukemia and in the treatment of lymphoma, and is tried in the management of myelodesplasia. The chapter discusses various methods of analysis such as compendial methods (British pharmacopoeia methods, and United States Pharmacopoeia methods), and reported methods of analysis (titrimetric method, ultraviolet spectrometric methods, chemiluminescence method, polarographic methods, voltammetric method, and chromatographic methods). A radioimmunoassay method for cytarabine and other arabino nucleoside in blood plasma is described in which radiolabeled arabino-nucleoside and anti-arabino-nucleoside antibody are mixed with a sample, and radioactivity of free or antibody-bound arabino-nucleoside is counted. Cytarabine is not effective by mouth due to rapid deamination in the gastrointestinal tract; less than 20% of an oral dose is absorbed.

Proton NMR Spectrometric Analysis of Glibenclamide and Tolazamide and Some of Their Pharmaceutical Preparations

Abstract An analytical method is described for the assay of two important oral hypoglycemic agents, namely, glibenclamide (glyburide); and tolazamide; using PMR technique. The method is rapid, accurate, specific and precise. The principle of the method involves comparing the integral of a chosen signal in the PMR spectrum of the drug under investigation with that of the methylene group signal of the internal standard, benzyl benzoate.

Acetylcholine Chloride: Physical Profile

Publisher Summary This chapter presents the physical profile of acetylcholine chloride. The empirical formula of the acetylcholine chloride is C 7 H 16 ClNO 2 . Acetylcholine chloride is obtained as white or off-white hygroscopic crystals, or as a crystalline powder. The physical properties includes pH, solubility characteristics, crystallographic properties, thermal methods of analysis, spectroscopy and mass spectrometry are discussed. Acetylcholine chloride is freely soluble in water, alcohol, propylene glycol, and chloroform, and is practically insoluble in ether. Acetylcholine chloride is very hygroscopic and extremely soluble, giving a solution of high viscosity. For this reason, it is difficult to prepare crystals appropriate for X-ray analysis. Aqueous solutions of acetylcholine chloride are found to be unstable. Such solutions are decomposed by heat, and are incompatible with alkalis and acids. The mass spectrum of acetylcholine chloride is obtained utilizing a Shimadzu PQ-5000 mass spectrometer, with the parent ion being collided with helium carrier gas and the mass spectrum and the mass fragmentation pattern is shown in the chapter.

Acetylcholine Chloride: Analytical Profile

Publisher Summary This chapter presents several methods employed for the analysis of acetylcholine chloride. These includes titrimetric methods of analysis, electrochemical methods of analysis, spectrophotometric methods of analysis, chromatographic methods of analysis, and other methods of analysis are also discussed in the chapter. Titrimetric methods of analysis include acidimetric methods and potentiometric methods. The transfer of acetylcholine ions across the interface between the gel electrode and water is studied by cyclic voltammetry, potential-step chronoamperometry, and potentiometry. Electrochemical method of analysis includes conductimetric methods, polarographic methods, voltammetric methods, coulometric flow titration methods, flow injection method, and amperometric methods are discussed. Spectrophotometric methods of analysis include infrared spectrophotometric method, photometric methods, mass spectrometric method, colorimetric methods, fluorimetric methods, and chemiluminescence methods. Chromatographic methods of analysis include thin layer chromatography (TLC), gas chromatography (GC), and several other methods are also presented in the chapter. Various other methods, such as ion-selective method, microwave methods, and microdialysis are also discussed in the chapter for the analysis of acetylcholine chloride.