Pharmaceutical Chemistry Journal (v.49, #9)

Succinate Receptors (SUCNR1) as a Potential Target for Pharmacotherapy by S. V. Okovityi; S. V. Rad’ko; E. B. Shustov (573-577).
A considerable number of reports have been published in recent years on G protein-coupled receptors, their distribution in the body, mechanism of activation, and potential pathways for pharmacological actions. Intermediates in carbohydrate, fat, and protein metabolism and the tricarboxylic acid cycle, operating as endogenous ligands for a large group of ex-orphan receptors, have active roles in regulating metabolic processes, while their synthetic analogs, operating as both agonists and antagonists, may have potential for the development of new pharmaceuticals for a wide range of diseases (diabetes mellitus, obesity, metabolic syndrome, autoimmune disorders, hypertension, myocardial hypertrophy and ischemia, neurodegenerative processes, liver diseases, etc.). The present review addresses GPR91 (SUCNR1) receptors, which have been identified in fatty tissue, liver, kidneys, heart, brain, retinal neurons, dendritic cells, and platelets, and which are regarded as physiological regulators and cell sensors for stress-induced damage and hypoxia.
Keywords: GPR91 receptors; SUCNR1 receptors; succinate; reamberin

Effects of Thioctic Acid on the Oxidative Status Tissues in Rheumatoid Arthritis in Rats by E. D. Kryl’skii; T. N. Popova; E. M. Kirilova (578-581).
Biochemiluminescence, aconitate hydratase activity, and citrate contents were studied in rat serum and muscle in normal animals and in experimental rheumatoid arthritis; the actions of thioctic acid on the background of the development of this pathology were also studied. The development of rheumatoid arthritis in rats was accompanied by increases in marker values and measures of biochemiluminescence, as well as decreases in aconitate hydratase activity, evidently due to the extreme generation of reactive oxygen species associated with the induction of pathology. Suppression of the activity of this enzyme was linked with the accumulation of citrate in the tissues of the experimental rats. Administration of thioctic acid to rats with rheumatoid arthritis was accompanied by changes in values towards the normal, which was evidently linked with the antioxidant action of this compound.
Keywords: rheumatoid arthritis; free-radical oxidation; aconitate hydratase; citrate; thioctic acid

Docking of a series of methanepyrido[1,2-a][1,5]diazocin[(-)-cytisine derivatives to the active center of the nicotinic acetylcholine receptor was used to generate a set of potential substances for the treatment of cognitive dysfunction. The results from these studies led to the conclusion that six of the 21 structures were potential inhibitors of the nicotinic acetylcholine receptor. Experimental testing confirmed that the study compounds had nootropic actions and allowed the most active of these to be selected for further investigation.
Keywords: molecular docking; virtual screening; receptor; inhibitor; neurodegenerative diseases

Synthesis and Neurotropic Activity of New Pyrimido[4′,5′:4,5]Thieno[2,3-b]Quinoline Derivatives by V. V. Dabaeva; M. R. Bagdasaryan; A. S. Noravyan; I. A. Dzhagatspanyan; I. M. Nazaryan; A. G. Akopyan (587-591).
New methods for preparing pyrimido[4′,5′:4,5]thieno[2,3-b]quinoline derivatives based on 3-cyanohexahydro-2-quinoline were developed. The neurotropic activity of these compounds was studied.
Keywords: synthesis; pyrimido[4′,5′:4,5]thieno[2,3-b]quinoline; neurotropic activity

Synthesis and Analgesic Activity of 3-Arylamino-1,2-Dihydro-3H-1,4-Benzodiazepin-2-Ones by V. I. Pavlovskii; I. Yu. Ushakov; T. A. Kabanova; E. I. Khalimova; V. Kh. Kravtsov; S. A. Andronati (592-597).
Interaction of 3-chloro-5-aryl-1,2-dihydro-3H-1,4-benzodiazepines with aromatic amines was used to synthesize 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with analgesic activity in the acetate acid writing test (ED50 0.007 – 3.2 mg).
Keywords: benzodiazepinones; analgesic activity; synthesis

Synthesis and Antimicrobial Activity of Thietanylpyrimidin-2,4(1H,3H)-Dione Acetanilides and Acetylhydrazones by S. A. Meshcheryakova; V. A. Kataev; I. Ya. Fattakhova; K. V. Nikolaeva; A. K. Bulgakov (598-601).
Alkylation of 6-methyl-1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione with chloroacetanilides yielded N-acetanilide derivatives. Interaction of 2-(4-methyl-2,6-dioxo-3-thietan-3-yl-3,6-dihydropyrimidin-1(2H)acetohydrazide with carbonyl compounds was used to synthesize arylaldehyde and ketone N-acetylhydrazones. The antimicrobial and antifungal activities of the compounds synthesized here were studied.
Keywords: thietane; pyrimidin-2,4-(1H,3H)-dione; N-acetanilides; N-acetylhydrazones; E, Z isomerism; antimicrobial and antifungal activity

Synthesis and Antibacterial Activity of 1-[2-(4-Aminosulfonylphenyl)Ethyl]-5-Aryl-4-Aroyl-3-Hydroxy-3-Pyrrolin-2-Ones by V. L. Gein; O. V. Bobrovskaya; R. T. Valiev; T. F. Odegova; G. A. Gartman (602-604).
Reaction of the methyl esters of aroylpyruvic acids with mixtures of 4-(2-aminoethyl)benzenesulfonamide and an aromatic aldehyde was used to synthesize 1-[2-(4-aminosulfonylphenyl)ethyl]-5-aryl-4-aroyl-3-hydroxy- 3-pyrrolin-2-ones. The structures of these compounds were verified by IR and 1H NMR spectroscopy and mass spectrometry. Their antibacterial activity was studied.
Keywords: 1-[2-(4-aminosulfonylphenyl)ethyl]-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones; synthesis; antibacterial activity

Preparation of Inclusion Complex Between Nifedipine and Ethylenediamine-β-Cyclodextrin as Nanocarrier Agent by Abolfazl Heydari; Mahsa Iranmanesh; Farideh Doostan; Hassan Sheibani (605-612).
Nifedipine (NIF) is a poorly water-soluble and a high photosensitive drug, which is among most efficient drugs for treating diseases such as hypertension and angina pectoris. The main purpose of this work was the preparation and study of the inclusion complex between NIF and ethylenediamine-β-cyclodextrin (NIF/EDA-CD). The NIF/EDA-CD complex has been prepared using the co-precipitation method and characterized by UV-Vis spectroscopy, dynamic light scattering (DLS), differential scanning calorimetry (DSC), thermogravimetric (TGA), and Fourier-transform infrared (FT-IR) spectroscopy in both solution and solid state. The 1 : 1 molar stoichiometry is confirmed by the continuous-variation Job’s plot and phase solubility diagram. The phase solubility diagram showed a complexation constant of 1019.62 M-1. In addition, supplementary data from solubility tests have demonstrated that the solubility of NIF in water greatly increased through complexation with EDA-CD, which is a result of the water-soluble EDA-CD host.
Keywords: ethylenediamine–cyclodextrin; nifedipine; nanocarrier; solubility; drug delivery

Phencyclidine (PCP, I) and many of its analogs have showed many pharmacological effects through several neurotransmitter systems. In addition to binding to the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, it also interferes with other brain functions. In this study, new derivatives (V – VII) were synthesized by changing aromatic moiety (phenyl, thienyl, and benzothiophene) and modifying cyclohexyl and piperidine rings (4-methylcyclohexyl and 3-piperidinol, respectively) of PCP. The acute and chronic pain activities of these new drugs were studied by using the tail immersion and formalin tests on mice and compared to control, PCP, and ketamine treated groups. The obtained results indicated that all new synthesized drugs showed better activity in decreasing acute thermal and chemical pains in tail immersion and formalin tests compared to PCP and ketamine. Also, compound VII (benzothiophene analog) produced more pronounced analgesic effects on acute thermal pain in tail immersion test, as well as compound V (thiophene analog)on acute chemical and chronic pains in formalin test as compared to other drugs.
Keywords: phencyclidine; ketamine; NMDA receptors; dopamine receptors; pain activity; tail immersion test; formalin test

Development and Validation of an Express Method for Assay of Water-Soluble Polysaccharides in Common Burdock (Arctium lappa L.) Roots by N. A. D’yakova; I. A. Samylina; A. I. Slivkin; S. P. Gaponov; A. A. Myndra (620-623).
An express method was developed for assay of water-soluble polysaccharides in common burdock (Arctium lappa L.) roots, with an analysis time of 3 h. The method was validated in terms of reproducibility, accuracy, and linearity, and this demonstrated that the method was accurate on reproduction, correct, and had a quite strictly linear relationship between the weight of the precipitate and the weight of the material analyzed using gravimetric determination of water-soluble polysaccharides in common burdock roots. The method can be used for rapid analysis of the quality of common burdock root and for the industrial production of inulin from this raw material.
Keywords: water-soluble polysaccharides; common burdock roots (Arctium lappa L.)

Antifungal Activity of the Extractives of Coleus Forskohlii Roots and Forskolin by Eugene Sebastian J. Nidiry; Girija Ganeshan; A. N. Lokesha (624-626).
Hexane, ethyl acetate and methanol extractives of Coleus forskohlii roots exhibit mycelial growth inhibition of Colletotrichum gloeosporioides and spore germination inhibition of Alternaria solani. Forskolin, a diterpene present in C. forskohlii exhibit dose dependent spore germination inhibition of A. solani, this being the first report on the antifungal activity of this compound. Estimation of forskolin in the extractives by HPLC showed that while hexane extractive contained 3.9% forskolin and ethyl acetate extractive contained 4.6% forskolin, while the methanol extractive did not contain forskolin. The results clearly show that forskolin is one of the antifungal compounds present in the plant.
Keywords: Coleus forskohlii ; antifungal activity; Colletotrichum gloeosporioides ; Alternaria solani ; forskolin

Review of Contemporary Gel-Forming Agents in the Technology of Dosage Forms by M. N. Anurova; E. O. Bakhrushina; N. B. Demina (627-634).
This review addresses the general principles of the classification of gel-forming agents, and the characteristics, properties, preparation techniques, and mechanisms of gel formation of the major groups of gel-formers used in producing dosage forms (derivatives of cellulose, carbopols, polyethylene oxides, silicones, poloxamers, alginates, κ -ginanes, bentonite clays, and chitosan), to facilitate selection of polymers for developing dosage forms as gels.
Keywords: gel-formers; classification; characteristics; area of use; gel preparation techniques

The efficacies of the antimicrobial conservants in a number of nonsterile medicinal formulations for oral use as syrups and solutions were evaluated, i.e., Klarisens® syrup 1 mg/ml, Él’kar® solution for oral use, 300 mg/ml, Lasolvan® syrup 15 mg/5 ml, and others. The quality of seven study samples containing conservants such as benzoic acid, methylparaben, propylparaben, sodium benzoate, and ethanol complied with the requirements of General Pharmacopeia Monograph OFS 42-0069-07 “Determination of the efficacy of antimicrobial conservants in medicines”. The results of the studies reported here were obtained using a modified deep plate inoculation method recommended by the State Pharmacopeia of the Russian Federation XII edition for determination of the microbiological purity of medicines. The modified deep plate method has potential for use as a supplementary method, and inclusion in the next edition of the State Pharmacopeia of the Russian Federation is recommended.
Keywords: antimicrobial conservant; medicine; efficacy

Studies of Carbomer Gels Using Rotational Viscometry and Spin Probes by A. N. Lyapunov; E. P. Bezuglaya; N. A. Lyapunov; I. A. Kirilyuk (639-644).
The rheological properties of Carbomer and Polycarbophil gels were studied in relation to pH, Carbomer concentration and brand, temperature, and dispersal medium composition. The study results permit rational selection of Carbomers as gel-forming agents. Gel formation occurring on neutralization of Carbomer with alkali did not lead to any increase in the viscosity of the gel dispersal medium; spin probes dissolved in it remained in the state of rapid isotropic rotation at the micro level, which provides conditions for rapid and complete release of drugs dissolved in these gels. In contrast to this, the rotational diffusion correlation time (τ-1) of the probe 4-amino-TEMPO in gels passed through a maximum at pH 7.1 – 8.7, which appeared to be due to interaction of the cation formed by protonation of the amino group of this spin probe with several neighboring carboxylate-anions of the Carbomer. Increases in temperature weakened this effect, while ethanol and N-methylpyrrolidone in the gel increased it. This interaction could decrease the release of some drugs, with decreases or prolongation of the efficacy of their pharmacological actions.
Keywords: Carbomer; Polycarbophil; gel; pH; structural viscosity; spin probe; rotational diffusion correlation time