Pharmaceutical Chemistry Journal (v.51, #3)

Organic Hydrogen Sulfide Donor Compounds with Cardioprotective Properties (Review) by N. I. Tkacheva; S. V. Morozov; B. B. Lomivorotov; I. A. Grigor’ev (165-174).
This review summarizes published data on organic hydrogen sulfide donor compounds, including hybrid compounds, and their roles in cardioprotection.
Keywords: hydrogen sulfide; organic H2S donors; hybrid compounds; cardiovascular system; cardioprotection

The Main Structural Types of Inhibitors of Matrix Metalloproteinases by L. E. Kapranov; A. N. Reznikov; Yu. N. Klimochkin (175-181).
This review addresses the main structural types of matrix metalloproteinase (MMP) inhibitors - hydroxamic acid derivatives, sulfonamides, bisphosphonates, compounds combining phosphoryl and hydroxamate groups, and functional derivatives of phosphonic and phosphinic acids. The selectivity of the inhibitory actions of these substances in relation to different types of MMP and the potential for the practical application of these substances in cancer treatment are discussed.
Keywords: matrix metalloproteinases; inhibitors; antimetastatic activity; carbamoylphosphonates; sulfones; hydroxamic acids

The Search for Pharmacologically Active Compounds Among the 2-Dialkylaminobenzimidazoles by O. N. Zhukovskaya; V. A. Anisimova; A. A. Spasov; D. S. Yakovlev; N. A. Gurova; A. F. Kucheryavenko; O. A. Salaznikova; V. A. Kuznetsova; D. V. Mal’tsev; A. A. Brigadirova; Ya. V. Morkovina; O. A. Solov’eva; V. V. Gurova; E. V. Reznikov (182-186).
Heating of substituted benzimidazole-2-sulfonic acids in the presence of excess quantities of secondary amines was used to synthesize dialkylaminobenzimidazoles. Experimental studies of potential antiarrhythmic, antiaggregation, hemorheological, AT1 angiotensin- and NHE-1-inhibiting, and antiserotonin activity identified active compounds. 1[-2-(5-Methyl)benzimidazole]pyrrolidine had greater NHE-inhibiting activity than zoniporide. 1-{[2-(5-Methoxy)benzimidazole]-4-N-methyl}piperazine dihydrochloride had greater antiaggregatory activity than acetylsalicylic acid, while 1-[2-(5-methyl)benzimidazole]piperidine was as active as cyproheptadine in terms of 5-HT2A antagonistic activity. 1-(2-Benzimidazole)pyrrolidine and 1-[2-(5-chloro) benzimadazole pyrrolidine dihydrochlorides had 5-HT3 antagonist activity equal to that of tropisetron..
Keywords: dialkylaminobenzimidazoles; synthesis; antiarrhythmic; antiaggregatory; hemorheological; NHE-inhibiting activity; 5-HT2A receptor blockers; 5-HT3 receptor blockers; angiotensin 1 receptor blockers

Synthesis and Analgesic and Antibacterial Activity of 5-aryl-4-aroyl-1-(4-acetylaminosulfonylphenyl)-3-hydroxy-3-pyrrolin-2-ones by V. L. Gein; O. V. Bobrovskaya; G. V. Seliverstov; R. R. Makhmudov; V. V. Novikova (187-190).
A three-component reaction of aroylpyruvic acid methyl ester with a mixture of an aromatic aldehyde and 4-aminobenzenesulfonylacetamide (sulfacetamide) was used to synthesize 5-aryl-4-aroyl-1-(4-acetylaminosulfonylphenyl)-3-hydroxy-3-pyrrolin-2-ones. The structures of these compounds were established by IR, NMR, and 1H spectroscopy, along with mass spectrometry. The analgesic and antibacterial activities of these compounds were studied.
Keywords: 5-aryl-4-aroyl-1-(4-acetylaminosulfonylphenyl)-3-hydroxy-3-pyrrolin-2-ones; synthesis; analgesic and antibacterial activity

Antinociceptive And Antimicrobial Activity of 1-Substituted 4,4,4-Trichlorobutane-1,3-Diones by N. Yu. Lisovenko; D. G. Chemadurov; S. Yu. Balandina; R. R. Makhmudov (191-192).
The analgesic and antimicrobial activity of 1-substituted 4,4,4-trichlorobutane-1,3-diones were studied.
Keywords: 1-Substituted 4,4,4-trichlorobutane-1,3-diones; antinociceptive activity; analgesic activity

Synthesis of N-Substituted (2,3-Dihydro-1,4-Benzodioxin-6-YL)Benzenesulfonamide Derivatives as Potent Antibacterial Agents and Moderate Enzyme Inhibitors by M. A. Abbasi; S. K. Farani; Aziz-ur-Rehman; S. Z. Siddiqui; I. Ahmad; R. Malik; M. Ashraf; Qurat-ul-Ain (193-199).
The present research work involved the reaction of 2,3-dihydro-1,4-benzodioxin-6-amine (1) and benzenesulfonyl chloride (2) under dynamic pH control at 10 using aqueous Na2CO3. This reaction yielded 2,3-dihydro-1,4-benzodioxin-6-yl)benzenesulfonamide (3), which was further substituted at N-position with various alkyl/aryl halides (4a – 4m) in N,N-dimethylformamide and catalytic amount of lithium hydride to obtain N-substituted (2,3-dihydro-1,4-benzodioxin-6-yl)benzenesulfonamides (5a – 5m). The projected structures of the synthesized derivatives were confirmed using various spectral techniques (IR, 1H NMR and EIMS). The synthesized derivatives were screened for antibacterial potential and inhibitory activity against lipoxygenase enzyme.
Keywords: 2,3-dihydro-1,4-benzodioxin-6-amine; sulfonamide; antibacterial activity, cholinesterase; lipoxygenase

Assessment of the Antioxidant Activity of Extracts of Allium schoenoprasum L. with an Experimentally Elevated Selenium Content by K. V. Bezmaternykh; T. I. Shirshova; I. V. Beshlei; N. V. Matistov; G. V. Smirnova; O. N. Oktyabr’skii; V. V. Volodin (200-204).
The effects of using selenium dressings on A. schoenoprasum on the antioxidant activity of extracts were studied. Treatment of seeds with sodium selenate led to minor increases in polyphenol levels in extracts and the expression of the antioxidant gene katG, but had no effect on the radical-binding (RBA) or chelating (CA) activity of extracts, not increasing their antioxidant activity in a microbial test system. Selenate added artificially to extracts produced statistically significant reductions in indicators such as the concentrations of polyphenols, RBA, CA, and, to a small extent, antioxidant activity in the microbial test system, but had no effect on the ability of extracts to stimulate expression of the katG gene.
Keywords: selenium; polyphenols; antioxidant activity

Abies pindrow Royle (Himalayan silver fir, family Pinaceae) has a long tradition of use as anxiolytic but not investigated scientifically. Previously, antianxiety activity of chloroform extract (CE) and ethyl acetate fraction (EAF) of methanol extract of the plant have been reported at the dose of 400 and 50 mg/kg, respectively. CE and EAF were subjected to bioactivity-guided-fractionation using column chromatography with a view to isolate anxiolytic constituents. The antianxiety activity of test samples was assessed by comparing with control as well as standard drug, diazepam (2 mg/kg, p.o.) using the elevated plus maze model. Among six fractions (F1 – F6) of CE obtained after column chromatography, F2 and F3 exhibited significant antianxiety activity at doses of 45 and 40 mg/kg, respectively. Further column chromatography of F2 and F3 led to the isolation of maltol and dipalmitin. Column chromatography of EAF yielded five fractions (F1 – F5). F1 Exhibited antianxiety activity at the dose of 15 mg/kg. Column chromatography of F1 led to the isolation of gallic acid, maltol, p-coumaric acid, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, shikimic acid, pinitol, hesperitin, and apigenin. Among these compounds, maltol, gallic acid, p-coumaric acid, hesperitin, and apigenin exhibited antianxiety activity at doses of 100, 10, 30, 50 and 2 mg/kg, p.o., respectively.
Keywords: Abies pindrow ; anxiety; flavonoids; phenols; pinaceae

Tianma is the dried tubers of Gastrodia elata Bl. plant (Orchidaceae). Its active ingredient mainly consists of tianma glycosides, phenols, and phenolic glycosides and also contains sterols and their glycosides, polysaccharides, and some other compounds. In recent years, the pharmacological effects of tianma received increasing attention and the study achieved some results. Tianma based crude drugs produce sedative, analgesic, anticonvulsant, and other effects, and also influence the cardiovascular and immune systems. Tianma has always been a hot issue of Chinese medicine research, its main areas covering clinical applications, pharmacology, chemistry, and biology. This article reviews progress of G. elata studies in various aspects.
Keywords: Gastrodia elata ; chemical composition; pharmacological effects; clinical applications; market; analysis

Studies using 224 blood samples as examples showed that the use of solid-phase extraction and gas chromatography with mass spectrometric detection for screening blood provides reliable identification of a wide range of narcotic and pharmaceutical substances of forensic medical interest, including “designer” synthetic narcotics – methylenedioxypyrovalerone (MDPV), pyrrolidinovalerophenone (PVP), and their metabolites; cannabimimetic metabolites N-(1-carbamoyl-2-methylpropyl)-1-pentyl-1H-indazole-3-carboxamide (ABPINACA) and/or N-[(1-pentyl-1H-indazol-3-yl)carbonyl]valine methyl ester (AMB). The distribution of substances in different elusion fractions is given and dissociation constants (pKa) and coefficients of distribution in an octanol-water system (log P) are calculated.
Keywords: methylenedioxypyrovalerone; pyrrolidinovalerophenone; narcotic screening; cannabimimetics; blood; solid-phase extraction

Validation of a Method for Assay of Sulfur Hexafluoride in a New Contrast Agent by Gas Chromatography by S. V. Krivoshchekov; M. S. Lar’kina; S. S. Vlasov; L. A. Drygunova; A. M. Gur’ev; M. V. Belousov; M. S. Yusubov (222-225).
Amethod for assaying sulfur hexafluoride in a new contrast agent by gas chromatography is described. Detection was with an electron capture detector (ECD). Sulfur hexafluoride was extracted from samples using heptane as the solvent. The method was validated in terms of the following parameters: specificity, linearity, correctness, stability, and inter- and intralaboratory precision.
Keywords: sulfur hexafluoride; assay; gas chromatography

Development of a Method for Determining the Amino Acid Composition of the Pharmaceutical Substance “Glatiramer Acetate” by NMR Spectroscopy by N. E. Kuz’mina; S. V. Moiseev; V. I. Krylov; A. A. Kutin; V. A. Yashkir; V. A. Merkulov (226-229).
The acid hydrolysis procedure for glatiramer acetate was modified and the characteristic signals in the 1H and 13C spectra were identified, allowing its amino acid composition to be determined. The relative molar contents of amino acids in glatiramer acetate measured by HPLC-MS and by 13C and 1H NMR had close values. 13C NMR was found to be a more precise method for assaying the amino acid composition of glatiramer acetate than 1H NMR.
Keywords: glatiramer acetate; amino acid composition; acid hydrolysis; NMR spectroscopy

An iodometric method for determining the antiradical activity (ARA) of dihydroxybenzenes in the reaction with 2,2′-azobis-(2-amidinopropane) (AAP) peroxyl radicals (rOO ) in conditions close to those obtaining in biological systems was developed. A means of calculating relative rate constants of reactions of phenols with rOO from the kinetics of consumption of an inhibitor added at low concentration was proposed. The greatest levels of ARA were seen with resorcinol, orcinol, and hydroquinone, which are able to dissociate to form highly reactive mono-and bianionic forms of phenolate ions. A method of calculating relative rate constants of these reactions was proposed, based on the AAP - AAP peroxyl radical - phenol kinetic model.
Keywords: dihydroxybenzenes; antioxidants; peroxyl radicals of 2,2′-azobis-(2-amidinopropane) hydrochlorides; relative reaction rate constants

A Chromatographic Method for Assay of Sodium Caprylate in the Formulation “Albumin, Solution for Infusions” by E. V. Khlybova; E. S. Kormshchikova; A. V. Drobkova; I. V. Paramonov (235-238).
A method for assaying sodium caprylate content using gel filtration HPLC and recording of the refractometric detector signal is described. Validation studies demonstrated the suitability of the method. Inclusion of a spectrophotometer in the chromatography system provided for monitoring two parameters (“Sodium caprylate” and “Polymers and aggregates”) in a single test.
Keywords: human albumin; plasma; sodium caprylate; gel filtration HPLC

The stability and quality of pharmaceutical substances are assured by systematic evaluation using various analytical techniques. Biologically active compounds retain and exhibit maximum potency during their shelf life. Once the drug expiry period is crossed, deterioration, decrease of therapeutic activity, and increased toxicity can occur. The purpose of the present study was to develop a simple, rapid and reproducible analytical method for the determination of N-isonicotynoyl-N′-(2-fluorobenzal)hydrazone – a synthesized by us halogenated isoniazid derivative with high tuberculostatic activity – in aqueous phase, on the basis of RP-HPLC-PDA and UV/VIS spectrophotometry investigations. The proposed RP-HPLC-PDA procedure is characterized by short retention time (3.1 min), high precision (RSD < 3.52%), and good linearity (R 2 > 0.9941). HPLC patterns display well-resolved peaks without interference. Despite high linearity (R 2 = 0.9978) of the UV/VIS spectrophotometry, greater LOQ and LOD values indicated unsuitability of this method for the detection and quantification of N-isonicotynoyl-N′-(2-fluorobenzal)hydrazone at low concentrations (< 10 μg/mL).
Keywords: N-isonicotynoyl-N′-(2-fluorobenzal)hydrazone; RP-HPLC-PDA; UV/VIS; aqueous phase