The in vitro antitumor assay of 5-(Z)-arylidene-4-imidazolidinones in screens of AIDS-related leukemia and lymphomas.

Thirty-one different 5-(Z)-arylidene-4-imidazolidinones were tested on six AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma cell lines: RL, KD-488, AS283, PA682 and SU-DHL-7. The investigated compounds showed remarkable activity against ARL, compounds 3d and 5c proved to inhibit AS283 and SU-DHL-7 cell lines, respectively, both at a GI50 value of 0.03 microM. The 2-(2-carboxyphenylamino) series proved to be the most active members in this investigation. Compounds 6b and 6d showed GI50 (MGMID) values of 6.1 and 8.7 microM, respectively, against the studied six ARL.

Synthesis and biological evaluation of certain alpha,beta-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents.

A new series of 3,5-bis(arylidene)-4-piperidones, as chalcone analogues carrying variety of aryl and heteroaryl groups, pyrazolo[4,3-c]pyridines, pyridolo[4,3-c]pyrimidines, and pyrido[4,3-c]-pyridines, carrying an arylidene moiety, and a series of pyrano[3,2-c]pyridines, as flavone and coumarin isosteres, were synthesized and screened for their in vitro antiviral and antitumor activities at the National Cancer Institute (NCI). Compounds 9 and 18 proved to be active against herpes simplex virus-1 (HSV-1), while compound 13 showed moderate activity against human immunodeficiency virus-1 (HIV-1). Compounds 14, 26, 28, 33, and 35 exhibited a broad spectrum antitumor activity. In addition, compounds 26, 33, and 35 proved to be of moderate selectivity toward leukemia cell lines. The pyrano[3,2-c]pyridines heterocyclic system proved to be the most active antitumors among the investigated heterocycles.

The voltammetric study and determination of ramipril in dosage forms and biological fluids.

The voltammetric behavior of ramipril was studied using cyclic voltammetry, direct current polarography (DCt), differential pulse polarography (DPP) and alternating current polarography (ACt). Ramipril developed well-defined cathodic waves in Britton-Robinson buffers over the pH range 6-12. The waves were characterized as being diffusion-controlled, irreversible and partially affected by adsorption phenomenon. The diffusion-current constant (Id) was 1.24 +/- 0.02. The current-concentration plots were rectilinear over the range 10-50, 4-40 and 0.16-12 micrograms/ml in the DCt, DPP and ACt modes, respectively, with a minimum detectability (S/N = 2) of 0.02 microgram/ml (4.8 x 10(-8) M) using the latter mode. The proposed method was successfully applied to the determination of ramipril in commercial tablets. Hydrochlorothiazide, which is frequently co-formulated with ramipril, did not interfere with the assay. Furthermore, the proposed method was applied to the determination of ramipril in urine and plasma adopting the ACt technique. The percentage recoveries were 97.12 +/- 0.56 and 94.97 +/- 0.62%, respectively. A pathway for the electrode reaction was proposed.

Methods of analysis of 4-quinolone antibacterials.

A comprehensive review with 270 references for the analysis of the members of an important class of drugs, 4-quinolone antibacterials, is presented. The review covers most of the methods described for the analysis of these drugs either per se, in dosage forms or in biological fluids.

The voltammetric behavior of nizatidine and its determination in biological fluids.

The voltammetric behavior of nizatidine (a newly introduced antiulcer drug) was studied using direct current (DCt), alternating current and differential pulse polarography (DPP). Well-defined cathodic waves were obtained over the whole pH range in Britton-Robinson buffers, in addition to 0.1 and 1 M HCl media. The main reduction wave was characterized as being irreversible and diffusion-controlled, although adsorption phenomena played a limited role in the electrode process. The current-concentration relationship was found to be rectilinear over the range 1x10(-5)-6x10(-4) and 2x10-6) -2x10(-4) M using DCt and DPP modes respectively, with a minimum detectability (S/N = 2) of 2x10(-7) M using the latter technique. The number of electrons involved in the reduction process was established, and the mechanism of electrode reaction was verified. The proposed method was successfully applied to determination of nizatidine in spiked human plasma and urine and the percentage recoveries were 96.12+/-0.40 and 97.12+/-0.17, respectively.

Determination of (S)(-)-cathinone by spectrophotometric detection.

Previous studies on the Khat plant (Catha edulis, Celastraceae) illustrated the importance of using freshly harvested young shoots and leaves such that cathinone, the principle active component and Schedule I controlled drug contained within the plant, could be suitably isolated and identified. The purpose of this work was to develop a quantitative analytical technique for the determination of cathinone. The proposed method is based on treating the reductant cathinone with copper(II)-neocuproine reagent in sodium acetate-buffered medium followed by measuring the absorbance of the copper(I)-neocuproine complex at 455 nm. The calibration plot is linear in the range 0.08-25 micrograms ml-1 with a detection limit of 0.08 microgram ml-1. The precision of the method, expressed as the relative standard deviation, is 1.35% for 10 micrograms ml-1 cathinone. Good recoveries have been obtained in applying the method to the analysis of cathinone in Khat leaves.

Synthesis and biological evaluation of new cyclopenteno[b]thiophene derivatives as local anesthetic and antiarrhythmic agents.

A series of ethyl 2-substituted amino-cyclopenteno[b]thiophen-3-carboxylates was synthesized as a carticaine analogues and evaluated for their local anesthetic and antiarrhythmic activity. Compounds ethyl 2-[1-oxo-2-(ethylamino)ethylamino]-(4a), ethyl 2-[1-oxo-2-(n-propylamino)-ethylamino]-(4c), ethyl 2-[1-oxo-2-(4-methylpiperazino)ethylamino]-(4e), ethyl 2-[1-oxo-2-(ethylamino)propylamino]-(5a) and ethyl 2-[1-oxo-2-(n-propylamino)propylamino]cyclopenteno[b]thiophen++ +-3-carboxylate (5c) proved to possess local anesthetic and antiarrhythmic activity comparable to carticaine and lidocaine. The active compounds exert their antiarrhythmic potency via blocking Na+ channels as in case of 5c or blocking Ca+2 channels as in case of 4a, 4c and 5c. Compound 4e exhibited a dual mechanism by blocking both Na+ and Ca+2 channels.

Spectrophotometric determination of methoxamine using cerium(IV) in presence of sodium lauryl sulphate and rhodamine-B.

A sensitive spectrophotometric assay has been developed for the determination of methoxamine in pure dosage form and in its pharmaceutical preparations. The method is based on the acidic oxidation of methoxamine with cerium(IV) in the micellar medium of sodium lauryl sulphate at 96 degrees C. The reaction yields a water-soluble purple product which can be quantified spectrophotometrically at 505 nm. The calibration curve was linear between 1.0 and 20 micrograms ml-1 with a limit of detection 0.5 microgram ml-1. The molar absorptivity at 505 nm is 8.3 X 10(3) iota mol-1 cm-1. The method is simple and rapid since the product is measured directly in solution without extraction.

5-substituted-2-thiohydantoin analogs as a novel class of antitumor agents.

Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5-bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethylene and 2-methylene-4H-thieno[2,3-b][1]benzothiopyran-4-one, were evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3-morpholinomethyl-2-(2,3,4,6 -tetra-O-acetyl -beta-D-glucopyranosylthio)hydantoin proved to possess a broad spectrum antitumor activity against a wide range of different human cell lines of nine tumor subpanels causing both cytostatic and cytotoxic effects, resulting in full panel median growth inhibition (GI50) and total growth inhibition (TGI), with a median lethal concentration (LC50) at 15.1, 41.7 and 83.2 microM, respectively. On the other hand, compound 5-(5-bromo-2-thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3-phenyl-2- (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obtained tentative structure-activity relationships, may lead to more potent agents.

Colorimetric determination of astemizole in bulk and in its pharmaceutical dosage forms using flow injection.

A continuous flow spectrophotometric method for determining 0.5-100 micrograms ml-1 of astemizole in pure and in dosage forms is suggested. It depends on forming a pinkish orange product which can be quantified spectrophotometrically at 495 nm. The coloured product was due to the action of N-bromosuccinimide on astemizole in alkaline medium and in the presence of a cetyltrimethylammonium bromide micellar medium. The procedure is automated and solutions can be analysed at a rate of 167 h-1 with a relative error of about 1.25%. The limit of detection is 0.5 microgram ml-1 (approximately 1.09 x 10(-6) M). The method is evaluated by a recovery study and by the analysis of commercial formulations.

Differential pulse polarographic assay of tolmetin sodium capsules.

Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of tolmetin sodium in a capsule formulation (Tolectin--200 mg as the sodium dihydrate salt). Classical direct-current (DC) polarography has been employed to investigate the nature of the reduction occurring at the surface of the dropping mercury electrode (DME) using acetate buffer of pH 5.0 as the supporting electrolyte. The mean value of the results obtained by DPP expressed as a percentage of the stated amount, and the standard deviation, were found to be 99.87 +/- 0.43. The standard addition procedure used to assess the accuracy of the proposed method gave a mean percentage recovery of the total drug of 100.15 +/- 0.75%.

Coupling of TLC and UV-measurement for quantification of naproxen and its main metabolite in urine.

A simple sensitive method of high specificity and selectivity for quantitative determination of the non-steroidal anti-inflammatory drug naproxen and its main metabolite, 6-demethylated derivative, in biological specimens is described. Like naproxen, its metabolite absorbs maximally at 232 nm; this makes their simultaneous quantification, via direct UV-measurements at lambda max, in biological fluids quite impossible. Simple TLC-separation on silica gel F254 using chloroform + methanol (85:15, v/v) achieved the best fractionation of the unchanged drug and its metabolite from the matrix-contents of urine. UV-quantification of fractionated components could reach concentration levels of 0.2-3.0 micrograms ml-1 (ppm) in worked up urine samples. Varying levels of unchanged antiinflammatory drug and the phenolic metabolite could be accurately traced in urine samples following a 2.9 mg/kg oral dose after different time-intervals. Synthetic preparation of the metabolite by demethylation of naproxen is briefly mentioned.