Pharmaceutical Chemistry Journal (v.46, #6)

Synthesis and pharmacological activity of 10-alkylaminoethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazoles by V. A. Anisimova; I. E. Tolpygin; A. A. Spasov; D. S. Yakovlev; N. A. Kolobrodova; N. A. Gurova; O. A. Salaznikova; L. V. Naumenko; V. A. Kosolapov; L. V. El’tsova; T. M. Mitina; M. P. Voronkova; K. V. Lenskaya (325-330).
The synthesis of 10-chloroethyl-2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazole was described. The nucleophilic substitution of the chlorine atom by various amines was studied. As a result, 10-alkylaminoethyl-substituted derivatives of this tricycle containing alkylamines and 4-substituted piperazines were obtained. These compounds exhibited 5-HT2 antagonist activity; platelet antiaggregant properties; and moderate P2Y1-antagonist, antiarrhythmic, and hypoglycemic action.
Keywords: synthesis; 2,3,4-10-tetrahydropyrimido[1,2-a]benzimidazole; antiaggregant activity; antiarrhythmic action; 5-HT2 antagonist activity; hypoglycemic properties; P2Y1-antagonist action

Synthesis and biological properties of new derivatives of 2-arylpyrrolidinecarbonitriles and pyrrolidinecarboxamides by S. P. Gasparyan; M. V. Alexanyan; G. K. Arutyunyan; V. E. Oganesyan; V. V. Martirosyan; R. V. Paronikyan; G. M. Stepanyan; A. O. Martirosyan (331-333).
A series of new analogs of 2-arylpyrrolidinecarbonitriles were synthesized under phase-transfer catalysis conditions. New analogs of pyrrolidinecarboxamides were synthesized based on these carbonitriles. Biological evaluation showed that the synthesized derivatives of pyrrolidinecarbonitriles and pyrrolidinecarboxamides possessed moderate anticancer activity.
Keywords: cyclic amino acids; proline; phase-transfer catalysis; intramolecular cyclization; acylation; pyrrolidine

Interaction of 2-mercaptobenzimidazole derivatives with sigma-1 receptors by E. V. Ryaskina; M. V. Voronin; S. B. Seredenin (334-336).
The interaction of afobazole and its main metabolite M-11 {2-[2-(3-oxomorpholin-4-yl)ethylthio]-5-ethoxybenzimidazole hydrochloride} with sigma-1 (σ1) receptors was studied in vitro in radioligand binding experiments on human T-cell lymphoblast-like cell line. Afobazole exhibited ligand properties towards σ1 receptors with IC50 = 7.1 × 10–6 M. For M-11, the corresponding value was IC50 = 9.6×10–4 M. Experiments in vitro on CD-1 mouse brain homogenate established that afobazole interacted with σ1 receptors (IC50 = 1.37×10–5 M) whereas M-11 did not show affinity towards σ1 receptors (IC50 > 5×10–4 M). Radioligand analysis results on mongrel CD-1 mice confirmed the results obtained on human T-cell lymphoblast-like cell line and led to the conclusion that σ1 receptors did not contribute to the pharmacological effects of M-11.
Keywords: afobazole; afobazole metabolite; σ1 receptor; radioligand binding

3-(Arylsulfonyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidines containing substituents with an amine in the 6-position were synthesized. Their structure—activity (antagonist) relationship was studied with respect to serotonin 5-HT6 receptors. It was shown that 2-(methylthio)-3-(phenylsulfonyl)- and 2-(methylthio)-3-(3-chlorophenylsulfonyl)pyrazolo[1,5-a]pyrimidin-6-amines, the activity of which was comparable with 3-(arylsulfonyl)-2-(methylamino)pyrazolo[1,5-a]pyrimidin-6-amines and 3-(arylsulfonyl)-2-(methylamino)-and 3-(arylsulfonyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidin-7-amines that were reported earlier, were the most active picomolar ligands.
Keywords: pyrazolopyrimidines; substituents; serotonin 5-HT6 receptors; antagonists; structure—activity; pharmacophore model

Synthesis and antimicrobial activity of quaternized heterocyclic systems based on α-pyridoin and 2,2′-pyridyl by N. V. El’chishcheva; Yu. V. Shklyaev; Zh. A. Vnutskikh; Yu. S. Chekryshkin; T. F. Odegova (346-350).
A series of uni- and biquaternized derivatives of α-pyridoin and 2,2′-pyridyl were synthesized. Their antimicrobial activity (AMA) was studied with respect to Gram-negative (E. coli) and Gram-positive (S. aureus) bacterial strains. It was established that the AMA depended on the nature of the radical and the presence of an oxygen between the pyridyl rings. The maximum activity was observed for 2,3-bis-(N-dodecylpyridinium-2′-yl)quinoxaline dibromide.
Keywords: quaternization; antimicrobial activity; α-pyridoin; 2,2′-pyridyl; quinoxaline

Synthesis, antibacterial, and antioxidant activity of [3-(4-chlorophenyl)-3-(4-fluorophenyl)propyl]- substituted ammonium oxalates by N. S. Arutyunyan; L. A. Akopyan; N. Z. Akopyan; G. A. Gevorgyan; G. M. Stepanyan; R. V. Paronikyan; M. H. Malakyan; R. L. Agdzhoyan; S. A. Badzhinyan; A. A. Shakhatuni (351-355).
Reduction of 3-(4-chlorophenyl)-3-(4-fluorophenyl)propionitrile produced 3-(4-chlorophenyl)-3-(4-fluorophenyl)propylamine, the reaction of which with aromatic and heterocyclic aldehydes and subsequent reduction with NaBH4 yielded [3-(4-chlorophenyl)-3-(4-fluorophenyl)propyl]-substituted amines. Hydrolysis of the corresponding nitrile afforded 3-(4-chlorophenyl)-3-(4-fluorophenyl)propionic acid, acylation of the chloride of which with various amines led to amides that were reduced to amines. The corresponding ammonium oxalates were prepared from the amines. The antibacterial and antioxidant properties of the ammonium oxalates were studied. It was established that some of the compounds exhibited high antibacterial activity but in most cases did not neutralize superoxide radicals.
Keywords: reduction; 3-(4-chlorophenyl)-3-(4-fluorophenyl)propylamine; antibacterial and antioxidant activity; photochemiluminescent method

An alternative efficient road for the synthesis of 16α,17α-epoxy-pregn-4,9(11)-dien-21-ol-3,20-dione from 9α-hydroxy-androst-4-ene-3,17-dione via its Δ9-analog has been studied.
Keywords: Synthesis; 16α,17α-epoxy-pregn-4,9(11)-diene-21-ol-3,20-dione

Micellar electrokinetic chromatography was used to determine the content of indole-3-carbinol in aerial parts of some plants from the family Brassicaceae. It was established that the herb of Brassica napus L. and the leaves of Brassica rapa L. had high contents of indole-3-carbinol (from 1.4 to 1.9%). In view of the potential use of Brassica napus as a source of anticancer compounds, reversed-phase HPLC was performed and revealed a significant content of flavonoids with the major aglycons quercetin, kaempferol, and isorhamnetin.
Keywords: micellar electrokinetic chromatography; indole-3-carbinol; flavonoids; Brassicaceae

Isolation, identification, and nootropic activity of compounds in Alfredia cernua chloroform extract by I. V. Shilova; A. A. Semenov; N. V. Kuvacheva; N. I. Suslov; R. N. Mustafin (363-368).
The chemical composition of the CHCl3 fraction of the total extract (95% EtOH) of Alfredia cernua (L.) Cass aerial part included triterpene alcohols (α-amyrin, β-amyrin, moretenol, lupeol) and butyrolignan (arctiin) in addition to various simple phenols and organic acids and their esters. It was established that the triterpene alcohols and arctiin demonstrated marked nootropic activity that was comparable with that of the whole CHCl3 fraction.
Keywords: triterpene alcohols; arctiin; nootropic activity; Alfredia cernua (L.) Cass

A relationship between the composition of essential oils and their ability to inhibit the model reaction of cumene radical oxidation was established. It was shown that azulene-containing essential oils of chamomile, yarrow, and wormwood were capable of inhibiting the model reaction of initiated cumene oxidation, which was indicative of antioxidant activity. It was shown that the greater the content of chamazulene was, the higher the antioxidant activity of the essential oil was. Essential oil of yarrow had a high chamazulene content (26%) and the maximum antiradical activity of the studied samples.
Keywords: essential oils; radical oxidation; natural antioxidants; chamazulene

Chemical composition and pharmacological activity of Ruscus colchicus leaves by E. P. Kemertelidze; T. S. Muzashvili; M. M. Benidze; A. V. Tsaruk; Z. A. Khushbaktova; V. N. Syrov (372-375).
Phylloclades of Ruscus colchicus P. F. Yeo turned out to be a rich source of steroidal glycosides with the biosynthesis of up to 40 steroids. A total of 22 pure compounds were isolated and identified including 1 cholestanol, 17 furostanol, and 4 spirostanol glycosides, among which 16 appeared to be novel organic compounds. Attention was drawn to the high number of sulfated compounds including six furostanols, two spirostanols, and one cholestanol. A pharmacological investigation showed that an aqueous EtOH extract of R. colchicus leaves exhibited pronounced lactogenic action.
Keywords: steroidal glycosides; Ruscus colchicus ; lactogenic action

Regioselective N-acylation of arginine in oleum by N. A. Kravchenya; K. N. Sokolov; T. N. Sokolova; N. K. Sokolov (376-377).
Regioselective synthesis of N G-monoacyl and N G, N IG-diacyl derivatives of L-arginine including reaction of L-arginine with monocarboxylic acids (C7-C17) in oleum at 60 – 65°C was carried out. The yields of the target products were 80 – 97%. The proposed synthetic method was highly effective (process time ~30 min). The synthesized compounds can be used in medicine and veterinary medicine as controlled-release NO sources.
Keywords: L-arginine; oleum; regioselective synthesis

Piroxicam ex vivo release kinetics from zein/pectin delivery systems by D. T. Bobokalonov; Z. K. Mukhidinov; I. F. Rakhimov; F. M. Khodzhaeva; G. F. Kasymova; L. S. Liu (378-380).
Piroxicam ex vivo release kinetics from zein/pectin drug delivery systems were studied using rat cecum. The piroxicam release kinetic parameters were calculated using a first-order equation and the Peppas equation. The results indicated that diffusion of the therapeutic agent was the rate-limiting step in piroxicam release from the hydrogel microspheres. The created therapeutic drug forms based on biodegradable polymers were an alternative to the peroral administration of most drugs with limited bioavailability.
Keywords: pectin; zein; hydrogel; drug delivery system; ex vivo ; piroxicam

3-O-benzyl-1,2-O-isopropylidene-xylopentadialdose has emerged as structurally new antibacterial and anti-inflammatory agent. Therefore, various substituted bis-indolyl-(3-O-benzyl-1,2-O-isopropylidene-xylopentadialdose glucofuranose) derivatives were synthesized by addition of substituted xylopentadialdose with various substituted indoles. The structures of the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectroscopy techniques. All the synthesised compounds showed maximum zone of inhibition againt both Gram-positive and Gram-negative organisms. In the anti-inflammatory activity test, three compounds (1, 3 and 5) produced significant activity in a dose-dependent manner.
Keywords: 3-O-benzyl-1,2-O-isopropylidene-xylopentadialdose; antibacterial activity; anti-inflammatory activity

Quantitative determination of thiosens in a new liposomal drug form by E. V. Sanarova; A. P. Polozkova; I. G. Meerovich; A. V. Lantsova; I. V. Yartseva; O. L. Orlova; N. A. Oborotova (386-388).
A procedure for the spectrophotometric quantification of thiosens in a new lyophilized liposomal drug form containing lecithin, cholesterol, and PEG-2000-DSPE at a molar ratio of 1:0.22:0.002 in addition to sucrose solution (cryoprotector) at a lecithin:cryoprotectant mass ratio of 1:2 was developed. The influence of excipients on the analytical results and the observance of the Bouguer–Lambert–Beer law was evaluated.
Keywords: thiosens; liposomes; spectrophotometry; Bouguer–Lambert–Beer law