Pharmaceutical Chemistry Journal (v.41, #10)

Pharmacokinetics of curcuminoids contained in the phytopreparation arthroflex by M. V. Karlina; O. N. Pozharitskaya; S. A. Ivanova (513-515).
Curcuminoids are the main active components in the extract of curcuma roots (Curcuma longa), which is widely used as an anti-inflammatory agent. We have studied the bioavailability and determined the pharmacokinetic parameters of curcuminoids contained in the complex phytopreparation Arthroflex studied experimentally in vitro and in vivo. The release of curcuminoids from Arthroflex into a nonconventional biphase system modeling conditions in the gastrointestinal tract was investigated in vitro and the dissolution rate constants were calculated. The pharmacokinetics of curcuminoids was investigated in vivo. It was established that curcumin in the initial form was missing from the blood plasma, and only two metabolites of curcuminoids were found by thin layer chromatography. The pharmacokinetic parameters of the major metabolite were determined.

Test systems for in vivo and in vitro estimation of the risk and development of delayed neurotoxicity caused by organophosphorus compounds by O. A. Khodakovskaya; N. A. Vodolazskaya; L. D. Glukhova; S. I. Timofeeva; S. I. Dvoretskaya; E. I. Malochkina; S. V. Sadovnikov (516-518).
We have elaborated new test systems for rapid in vitro and in vivo estimation of the risk and prediction of the development of delayed neurotoxicity (DNT) caused by organophosphorus (OP) compounds. The test is based on rapid estimation of the DNT potential of an OP compound with respect to its ability to inhibit the activity of neurotoxic esterase in blood lymphocytes. The proposed system can be used for the early diagnostics of DNT in humans upon acute poisoning with OP compounds.

Synthesis and biological characterization of new N-acyl-thiazolidine-4-carboxylic acid derivatives by E. S. Krichevskii; L. M. Alekseeva; V. A. Parshin; M. A. Kalinkina; V. V. Chernyshov; V. G. Granik (519-522).
2-Amino-1-[[(4-methoxycarbonylthiazolidin-3-yl)carbonyl]methyl]pyridinium chloride, 3-amino-1-[[(4-methoxycarbonylthiazolidin-3-yl)carbonyl]methyl]pyridinium chloride, 6-(3-aminopyridinium-1-yl)-5-oxo-5,7a-dihydro-1H-pyrrolo[1,2-c]thiazol-7-olate, and 6-(4-aminopyridinium-1-yl)-5-oxo-5,7a-dihydro-1H-pyrrolo[1,2-c]thiazol-7-olate were synthesized via the interaction of 3-chloroacetylthiazolidine-4-carboxylic acid methyl ester with 2-, 3-, and 4-aminopyridines. The synthesized compounds show significant influence on the learning and memorizing processes in experimental animals. An analysis of this activity in the tests involving cholinergic compounds showed that these N-acyl-thiazolidine-4-carboxylic acid derivatives are capable of influencing the central cholinergic system.

Antitumor steroids: 2. Synthesis and biological activity of 11α-hydroxyestra-1,3,5,(10)-triene derivatives with bis-(2-chloroethyl)amino-containing substituents by V. M. Rzheznikov; L. E. Golubovskaya; O. N. Minailova; B. I. Keda; T. I. Ivanenko; V. P. Fedotov; L. P. Sushinina; T. A. Titova; V. N. Tolkachev; I. P. Osetrova; Z. S. Smirnova (523-526).
Antitumor steroids with a cytotoxic substituent attached to the steroid nucleus without participation of natural functional groups have been obtained by esterification of 3-acetates of 11α-hydroxy derivatives of estradiol and 17α-ethinylestradiol with para-[bis(2-chloroethyl)amino]phenylacetic acid using the carbodiimide method. Some substances of this series combine antitumor activity and antiestrogen properties.

Aseries of new spirocondensed indole derivatives has been synthesized and studied for the structure — activity relationship. Dihydrochlorides of indoline-(5′-bromoindoline)-3′-spiro-1-(1,2,3,4-tetrahydro)-β-carboline and-3-methyl-β-carboline were obtained via reduction of the previously synthesized 2′-oxy-indoline-(5′-bromoindoline)-3′-spiro-1-(1,2,3,4-tetrahydro)-β-carboline and-3-methyl-β-carboline hydrochlorides, followed by the treatment with an ether solution of hydrogen chloride.

Synthesis and blood coagulation properties of drotaverine derivatives by A. G. Mikhailovskii; E. V. Vikhareva; N. G. Ismailova; B. Ya. Syropyatov; M. I. Vakhrin (529-531).
Quaternary ammonium salts have been obtained via the reaction of drotaverine base and its tetrahydroisoquinoline derivative with alkyl iodides. Boiling of drotaverine with HBr leads to the cleavage of ethoxy groups with the formation of hydroxy groups. It is established that all the synthesized compounds increase blood coagulation. For the most active compounds, the effect reaches 26%.

Antioxidant activity and flavonoid composition of the new nootropic preparation polynoophyt by I. G. Nikolaeva; L. D. Dymsheeva; S. M. Nikolaev; G. G. Nikolaeva (532-535).
The antioxidant activity of the new nootropic preparation polynoophyt has been experimentally studied on a model of hypobaric hypoxia in animals. The flavonoid composition of polynoophyt has been determined, which includes apigenin, hesperidin, luteolin, naringenin, baicalin, quercetin, myricetin, kaempferol, and gallic acid.

A preclinical study of two complex phytopreparations based on Saint-Mary thistle (Silybum marianum) extract — sibektan (possessing hepatoprotective properties) and kamadol (producing antiinflammatory action) — has been carried out on various laboratory animals (male and female rats, mice, guinea pigs, rabbits, and dogs). The parent substances of both preparations have proved to be low-toxicity compounds for a single intragastric or intraperitoneal administration in mice, rats, and guinea pigs. The intragastric administration of sibektan parent substance in rats for 1 month in doses of 50, 500, and 1000 mg-kg also showed no significant toxicity. The intragastric administration of sibektan 0.1-g tablets in dogs for 4 months in doses of 20 and 200 mg-kg did not produce functional changes in the heart, liver, kidneys, blood, and nervous system of test animals. The intragastric administration of kamadol in rats in a dose of 10 ml-kg, in dogs in a dose of 3 ml-kg for 3 months, as well as the external application of kamadol oil in rabbits in a dose of 1 ml-kg for 3 months, did not produce general toxic and local irritant effects in animals. Kamadol did not cause specific long-term consequences (mutagen effect, allergic and immunotoxic reactions).

Flowers of marigold (Tagetes) species as a source of xanthophylls by V. I. Deineka; V. N. Sorokopudov; L. A. Deineka; M. Yu. Tret’yakov (540-542).
The accumulation of xanthophylls in flowers of marigold (Tagetes) species cultivated under conditions of the Belgorod region has been studied. Five cultivars representing three marigold species were investigated, including T. erecta (Rhodes and Orange Snow cultivars), T. patula (Bolero and Harmony) and T. tenuifolia (Red Gem). The overall xanthophyll content in the petals of flowers has been determined spectrophotometrically, while the composition of lutein diesters in each Tagetes species as well as the composition of anthocyanins in the flowers with claret spots have been studied by reverse phase HPLC. It is established that the total content of xanthophylls and their composition are close to the published data for analogous species growing in other regions of the world. It is shown that more than 90% of xanthophylls in flowers are retained upon drying and the content of lutein diesters in the dry material can exceed 15 mg/g.

Functional derivatives of tetramic acid: New approaches to the synthesis of heterotricyclic compounds by I. K. Sorokina; L. M. Alekseeva; V. A. Parshin; V. G. Granik (543-548).
A large group of 3-methylidene, 5-methylidene, and 3,5-dimethylidene derivatives, as well as pyrrolo-[3,4-b]indole and pyrrolo[3,4-b]quinoline derivatives, has been synthesized on the basis of pyrrolidine-2,4-dione (tetramic acid). Some of the synthesized 3,5-disubstituted pyrrolidine-2,4-diones exhibit anticonvulsant activity.

Synthesis of N-substituted aminomethylene-benzofuran-2-ones by E. K. Panisheva; L. M. Alekseeva; M. I. Evstratova; S. S. Kiselev; V. G. Granik (549-553).
A series of substituted 3-R-aminomethylenebenzofuranones has been synthesized via the reactions of 3-[(dimethylamino)methylene-and 3-ethoxymethylene]benzofuran-2-(3H)-one with various amino derivatives. The synthesized compounds offer a promising basis in the search for biologically active substances.

Features of acetylsalicylic acid hydration in tablets by V. V. Turov; V. N. Barvinchenko; A. S. Shalamai; V. A. Pokrovskii; V. K. Pogorelyi; A. V. Turov (554-557).
It is demonstrated that NMR in combination with a liquid-phase freezing technique can be successfully used for the investigation of hydration processes in tablets, depending on the production technology.

Quantitative analysis of the new biologically active natural substance shunlite by O. Yu. Vasil’eva; M. S. Goizman; G. B. Tikhomirova; A. S. Berlyand; A. S. Alikhanyan; A. V. Shevyakov (558-562).
Methods for the quantitative determination of chemical elements contained in shunlite — a new biologically active natural substance — have been developed. The proposed methods are characterized by high accuracy and reproducibility.

The elemental composition of klimont — a new native biologically active substance — has been determined by laser mass-spectrometry. It is established that klimont is characterized by a very low content of toxic elements such as As, Cd, and virtually complete absence of Pb and Hg.

The International Symposium on Medicinal Chemistry (ISMC), which is organized in Europe every two years, summarizes the advances and outlines the prospects in this field. In 2004, the 18th ISMC was held in Copenhagen and Malmö, two neighboring cities of Denmark and Sweden, respectively, which are separated by Öresund and connected by a 15-km bridge over this strait.