Pharmaceutical Chemistry Journal (v.44, #12)

The cytotoxicities of capecitabine (Lab Tutour, Argentina) and xeloda (Roche) have been compared with respect to MCF-7 (human breast cancer cell line), HT-12 (colon cancer), and rat thymocytes by the MTT test. The cytotoxic activities of both drugs were the same and were highly selective with respect to the tumor cells. The sensitivity of the cells to the cytostatics increased in the order thymocytes < HT-12 < MCF-7.
Keywords: capecitabine; cytotoxic activity; MCF-7; HT-q12; thymocytes

The main trends in the development of the chemistry of α-, γ-, and δ-carbolines are generalized. Syntheses of carbolines based on pyridine derivatives (including the Fischer synthesis, Graebe—Ullmann reaction, thermal decomposition of azides, photochemical cyclization of anilinopyridines, arylation of substituted pyridines and piperidones, etc.) and based on indole derivatives are described. Published data about the biological activity of compounds belonging to these series are summarized.
Keywords: pyridoindoles (carbolines); Fischer synthesis; Graebe—Ullmann reaction; azides; pyridines; indoles; Diels—Alder intramolecular heterocyclization

Synthesis and anti-influenza activity of synthetic ribonucleases by L. S. Koroleva; N. S. Svishcheva; E. A. Burakova; N. V. Gribkova; N. P. Schmeleva; L. M. Rustamova; V. M. Sabynin; V. N. Sil’nikov (679-682).
The acute toxicity and antiviral activity of synthetic ribonucleases with various structures have been studied. It is established that synthetic ribonucleases exhibit low toxicity with respect to MDCK cell cultures and inhibit to different extents the reproduction of influenza A and B type viruses.
Keywords: synthetic ribonucleases; antiviral activity

The compositions of biologically active substances in Euphrasia brevipila Burn. et Gremli (Scrophulariaceae) extracts obtained using solvents with different polarities have been investigated. It was established that the composition of isolated substances varied depending on the extractant polarity. Only phenolcarboxylic acids were found in ether, chloroform, and ethylacetate extracts. Aqueous, ethanol, and DMSO extracts contained also flavonoids and iridoids. The difference in the compositions of biologically active substances was confirmed by UV spectral characteristics of extract solutions with added complexants. The maximum antibacterial activity with respect to Staphylococcus aureus and Escherichia coli was observed for extracts obtained using the nonpolar solvents petroleum ether and chloroform (in 1:320 dilution). The bacteriostatic activity of the extracts decreases with increasing solvent polarity in the order n-butanol—ethanol—water—DMSO.
Keywords: Euphrasia brevipila herb; extracts; UV spectral characteristics; antibacterial activity

Reactions of quinazoline and its 4-oxo- and 4-chloro-substituted derivatives with nucleophiles by Yu. A. Azev; B. V. Golomolzin; S. V. Shorshnev (687-690).
Reaction of quinazoline (I) with 2-methylindole, pyrogallol, and 1-phenyl-3-methylpyrazol-5-one in the presence of acid led to the formation of C-4 adducts II, III, and V. Adduct IV was obtained by heating I with 1,3-dimethylbarbituric acid without acid catalysis. 1-Phenyl-3-methylpyrazol-5-one reacts with I without acid catalysis with the formation of dipyrazolylmethane VI. 4-Chloroquinazoline VIII reacts with 1-phenyl-3-methylpyrazol-5-one to yield 4-(1-phenyl-3-methyl-5-oxopyrazol-4-yl)quinazoline IX and dipyrazolylmethane VI. Heating VIII with 2-methylindole leads to formation of 4-(2-methylindol-3-yl)quinazoline X and tris(2-methylindol-3-yl)methane XI. The proposed structures were confirmed by NMR spectral data.
Keywords: Quinazoline; chlorine-containing derivatives; reactions with nucleophiles; 2D-NOESY spectra

Drugs in immediate-release dosage forms that appear in the Essential Drug List and List of Additional Medical Maintenance of Preferential Categories of Citizens were classified. The results suggest that a satisfactory bioequivalence test for them may be based on an in vitro dissolution test according to WHO recommendations.
Keywords: Biopharmaceutics classification system; bioequivalence; in vitro method; classes of drugs; essential drug list

Synthesis, characterization, antibacterial and antifungal activity of thienopyrimidines and triazolothienopyrimidines by S. I. Panchamukhi; A. K. Mohammed Iqbal; A. Y. Khan; M. B. Kalashetti; I. M. Khazi (694-696).
Aseries of novel triazole fused tetracyclic thienopyrimidines (III – X) were synthesized from the corresponding precursor 5-amino-4-cyano-3-methylthiophene-2-carboxylic acid ethyl ester I. The precursor were in turn prepared via the Gewald reaction. Structures of all the newly synthesized compounds were characterized by spectral and analytical data. All the tested compounds displayed promising antibacterial and antifungal activities.
Keywords: Triazolothienopyrimidines; Gewald reaction; antibacterial activity; antifungal activity

Structure of chemical compounds, methods of analysis and process control by N. A. Alekseev; A. M. Drobyshevsky; D. A. Rozhdestvensky (697-701).
A procedure for the rapid determination of nimesulide (N) and its active metabolite (M1) [4′-nitro-2′-(4-hydroxyphenyloxyphenyl)methanesulfonamide] in human serum that includes solid-phase extraction with octylsilyl-silica gel followed by gradient reverse-phase HPLC with diode-array detection has been developed and validated. The ranges of linearity for the determination of M1 and N were 20.0 – 4,000.0 and 50.0 – 10,000.0 ng/mL, respectively; the limits of detection (3σ), 13 and 10 ng/mL, respectively. Long-term stability of the analytes in biosamples and the stability of samples after the preparation procedure were 1 month and 48 h, respectively. The procedure was used for bioequivalence studies of drugs containing N.
Keywords: chromatography; solid-phase extraction; nimesulide; human blood serum

Development of a chromatographic method for quantitative analysis of phenibut in biological samples by I. N. Tyurenkov; V. N. Perfilova; L. A. Smirnova; A. F. Ryabukha; E. A. Suchkov; S. A. Lebedeva (702-704).
An ion-pair chromatography method is developed using a reversed-phase C18 column with UV detection for the quantitative analysis of phenibut. The proposed method possesses sufficient selectivity and high sensitivity that enable its effective use during pharmacokinetic studies of phenibut in addition to other GABA derivatives in biological samples.
Keywords: phenibut; quantitative analysis; HPLC

The electrochemical behavior of antibiotic drugs, clindamycin hydrochloride (I) and its phosphate salt (II), on carbon paste electrode (CPE) is thoroughly investigated. Chemical and electrical parameters affecting the adsorption stripping voltammetry (ASV) measurements are optimized. Two different modes of sweep, viz., differential pulse (DP) and square wave (SW), are compared over a potential range of +400 to +1100 mV in the presence of 0.04 M Britton – Robinson buffer (pH 10) with an accumulation time of 30 s, scan rate of 100 mV/s, and pulse amplitude of 30 mV. The responses are linear over a concentration range of 86 – 430 and 90 – 813 ng/ml for I and 86 – 516 and 172 – 1030 ng/ml for II in the DP and SW sweep modes, respectively. The limits of detection (with correlation coefficients given in brackets) are as follow (ng/ml): 32.60 (0.998) and 90.73 (0.994) for I and 43.51 (0.997) and 83.02 (0.996) for II in the DP and SW sweep modes, respectively. The DP method has been applied successfully to determining the active ingredients in pharmaceutical preparations and in spiked urine with mean percentage recoveries of 99.24 ± 2.14 and 98.66 ± 2.38, respectively.
Keywords: Clindamycin; adsorption stripping voltammetry; carbon paste electrode