Pharmaceutical Chemistry Journal (v.43, #1)

Effects of cholesterol and its esters on transdermal penetration of phenazepam by I. A. Kravchenko; N. S. Novikova; V. B. Larionov; E. S. Pavlovskaya (1-3).
Cholesterol and its esters with aliphatic acids were studies as agents increasing the transdermal penetration of phenazepam when given transdermally in mice. Drug penetration was measured in terms of its pharmacological action (anticonvulsive effect on intravenous administration of 1% corasole). These studies showed that of the compounds studied, cholesteryl pelargonate had the greatest enhancing effect.
Keywords: Cholesterol; phenazepam; transdermal medicinal formulations

The reaction of 2-methyl-1-(p-tolyl)propanol-2 with N-alkyl-, N-benzyl-, and N-arylcyanacetamides was used to synthesize 2-(3,3,7-trimethyl-3,4-dihydroisoquinolyl-1)ethanoic acid amides. Investigations showed that tertiary amides formed from cyclic amines (morpholine, piperidine, etc.) had hypertensive actions, while all the other amides had hypotensive effects). The most active compound decreased arterial pressure by 46 mmHg and the duration of action was 90 min.
Keywords: Synthesis; (3,4-dihydroisoquinolyl-1)ethanoic acid amides; hypertensive and hypotensive effects.

Studies of the antioxidant and antihemolytic activity of quinoline derivatives in a model of oxidative damage to erythrocyte membranes by M. G. Malakyan; S. A. Badzhinyan; L. A. Vardevanyan; D. S. Grigoryan; D. É. Egiazaryan; A. A. Avetisyan; I. L. Aleksanyan; L. P. Ambartsumyan; K. S. Sargsyan (7-10).
New benzo-substituted 4-(aminophenylamino)-2-methylquinolines, 3-substituted 4-hydroxy(chloro and mercapto)quinolines, and thienoquinolines were synthesized. A model system based on oxidative damage to erythrocyte membranes induced by the combined actions of hydrogen peroxide and ionizing radiation was used to study the antihemolytic effects of these compounds as a means of assessing their antiradical/antioxidant properties. In the absence of x-rays, substances of the 3-substituted 4-hydroxy(chloro and mercapto)quinoline and thienoquinoline series were found to have marked antihemolytic effects, associated with significant influences on the structural stability of erythrocytes. However, with irradiation, the membrane-protecting effects were more marked with benzo-substituted 4-(aminophenylamino)-2-methylquinoline derivatives.
Keywords: Benzo-substituted quinolines; antioxidant and antihemolytic activity

Synthesis and antibacterial activity and antifungal activity of 2-R-4-R′-quinolines by A. V. Zimichev; M. N. Zemtsova; P. L. Trakhtenberg (11-12).
2-R-4-R′-quinolines, where R is a thienyl-2,2,2′-bithienyl-5-yl, or 1,1′-biphenyl-4-yl group and R′ is an azidocarbonyl- or carboethoxyamino group, were found to have antimicrobial activity against the diphtheria bacillus and Staphylococcus P-209.
Keywords: Synthesis; substituted quinolines; antibacterial and antifungal activity

Synthesis and anti-inflammatory, analgesic, and antipyretic activities of N-[β-(p-substituted benzoyl)ethyl]amino acids by A. G. Agababyan; G. A. Gevorgyan; A. E. Tumadzhyan; R. A. Akopyan; S. A. Aristakesyan (13-15).
Alkylation of a number of α-amino acids, as well as β-phenyl-β-alanine and γ-aminobutyric acid, with the hydrochlorides of p-substituted β-diethylaminopropiophenones resulted in the synthesis of N-[β-(p-substituted benzoyl)ethyl]cysteine, threonine, methionine, isoleucine, asparagine, and glutamine, along with β-phenyl-β-alanine, and γ-aminobutyric acid. The anti-inflammatory activities of the resulting compounds were studied; several of them had moderate anti-inflammatory activity.
Keywords: N-[β-(p-substituted benzoyl)ethyl] amino acid derivatives; synthesis; anti-inflammatory activity

The synthesis of 3-benzamido-1-(4-(2-methoxyphenyl) piperazin-1-yl)-propyl-2-isopropylcarboxamide (BPC) was accomplished by treating N-3-(4-(2-methoxyphenyl)piperazin-1-yl)-propyl-2-isopropylphthalimide with isopropylamine in dimethylformamide at room temperature. The compound was characterized spectroscopically. At concentrations of 0.05 and 0.1 mg/ml, 3-benzamido-1-(4-(2-methoxyphenyl)piperazin-1-yl)-propyl-2-isopropylcarboxamide (BPC) produced a significant inhibition of oxytocin (p < 0.05) and acetylcholine (p < 0.0001) induced contractions of the uterine smooth muscle in non-pregnant rats in a dose-dependent manner. From the results obtained it may be inferred that this compound is probably acting via muscarinic receptors.
Keywords: Tocolytic activity; preterm labor; antagonist; carboxamide; synthesis

2-Amino-5-sulfanyl-1,3,4-thiadiazoles: a novel series of anti-inflammatory and analgesic agents by Jitendra Sainy; Ganesh P. Mishra; Rajesh Sharma; Subhash C. Chaturvedi (19-24).
2-Amino-5-sulfanyl-1,3,4-thiadiazole derivatives were synthesized via the interaction of 2-amino-5-sulfanyl-1,3,4-thiadiazole, Ar-Cl, and benzene sulfonamide/benzene sulfonyl chloride. Twelve compounds were synthesized, out of which six compounds show significant anti-inflammatory and analgesic activity and were devoid of gastrointestinal side effects (ulcerogenic effect), which zre the most frequent adverse reactions associated with orally ingested anti-inflammatory or antiarthritic agents.

Synthesis and analgesic activity of (2,3-diphenyl-1H-indol-5-YL)piperazin-1-yl methanone derivatives by A. O. H. El-Nezhawy; S. I. El-Naem; S. A. Galal; H. I. El-Diwani; O. M. E. Abdel Salam; A. R. Baiomy (25-29).
Series of 1,4-disubstituted piperazine and of N,N-disubstituted ethylenediamine having the 2,3-diphenyl- 1H-indole-5-carbonyl group as one of the two substituents were prepared. Compounds 3, 4, 11, 15 – 17, and 20 – 22 were tested for analgesic activity. After ip administration all compounds induced significant visceral antinociceptive activities where acetic acid-induced writhing was significantly reduced by all compounds.
Keywords: 2,3-diphenylindole; piperazine; ethylenediamine; analgesic activity

Novel 4,6-diaryl-4,5-dihydro-3-hydroxy-2[H]-indazoles 9 – 16 and 4,6-diaryl-4,5-dihydro-2-phenyl-2Hindazol-3-ols 17 – 24 are effectively synthesized by a solid-state reaction procedure in the presence of NaHSO4 ⋅ SiO2 catalyst under microwave irradiation. All the synthesized compounds are characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (1H and 13C), D2O exchanged 1H NMR, and two-dimensional HSQC spectroscopic technique. An in vitro antibacterial activity study is carried out against clinically isolated bacterial strains, namely Bacillus subtilis and Micrococcus luteus, and antifungal activity against clinically isolated fungal strains, namely Aspergillus niger, Candida albicans, Candida 6, and Candida 51. Structure-activity relationship results for these 16 compounds have shown that all the compounds 9–24 exerted excellent antibacterial activity. Compounds having electron-withdrawing functional groups 11, 12, 14, 16, 19, 20, 22, and 24 recorded outstanding antifungal activity. The obtained results may be used as a key step for the building of new chemical compounds with interesting antimicrobial profiles comparable to that of the standard drugs.
Keywords: Solid-state synthesis; 4,6-diaryl-4,5-dihydro-3-hydroxy-2[H]-indazoles; 4,6-diaryl-4,5-dihydro-2-phenyl-2H-indazol-3-ols; antibacterial activity; antifungal activity

Experiments on animals (white rats) showed that “Ecdysterone-80” has a beneficial neurohormonal profile in experimental chronic cardiac failure (CCF), decreasing and in terms of some measures eliminating the hormone-transmitter imbalances characteristic of CCF. In addition, the study compound significantly decreased lethality among the animals and prevented the development of myocardial hypertrophy. These results may be of value for scientific investigations and for the introduction of production technology for a new pharmaceutical agent containing ecdysteroids from S. coronata with marked adaptogenic, gastroprotective, and antihypoxic actions (see communication I), along with cardioprotective properties.
Keywords: Ecdysterone-80; cardioprotective actions

The analgesic properties of the “CF” oil preparation extracted from safflower (Carthamus tinctorius L.) seeds were studied. The local anesthetic lidocaine and the tricyclic antidepressant amitriptyline, which induce complete block of the sciatic nerve, were used as positive controls. The actions of CF were associated with significant decreases in the nociceptive and proprioceptive functions of the sciatic nerve in mice. At a dose of 0.1 ml, this agent was sufficient to produce partial local anesthesia of the hindlimb, innervated by the sciatic nerve, without producing any toxic side effects. Thus, CF is a natural local anesthetic with moderate analgesic activity mediated by influences on the serotoninergic and monoaminergic pathways. CF may occupy a leading place among local anesthetics used in traditional medicine, particularly in pharmacotherapy and acupuncture, as well as medical massage.
Keywords: CF from safflower (Carthamus tinctorius L.) seeds; analgesic properties.

Steroid compounds from Yucca gloriosa L. introduced into Georgia and their applications by É. P. Kemertelidze; M. M. Benidze; A. V. Skhirtladze (45-47).
A plantation of Yucca gloriosa L. (mound-lily yucca) was created in eastern Georgia as a source of the sapogenin tigogenin and for raw material for the synthesis of steroidal hormone preparations of the 5α series. Leaves drying on the lower tier of the living plant contained only spirostanol glycosides. The dominant components of yuccaloesides A, B, and C were extracted from these, along with the new compound 3-O-α-L-rhamnopyranoside(1→4)-O-β-D-xylopyranosyl(1→3)-O-[β-D-glucopyranosyl(1→2)]-O-β-D-gluc opyranosyl(1→4)-O-β-D-galactopyranosyl 25R,5α-spirostan-3β-ol. Total glycosides from leaves drying on living plants were used to prepare a potential antimycotic substance for external application, Gloriofucin.
Keywords: Steroid compounds from Yucca gloriosa L.; preparation; application

Chemical composition of couch grass and studies of its antioxidant activity in allergic contact dermatitis by A. P. Petrova; E. A. Krasnov; E. V. Saprykina; Yu. A. Subbotina; E. V. Ermilova (48-50).
The composition of biologically active substances of aqueous extracts of couch grass was studied and the following groups of biologically active substances were identified: coumarins, iridoids, saponins, slimes, polysaccharides (including inulin), ascorbic acid and β-carotene, flavonoids (rutin, hyperoside, baicaleine) phenocarboxylic acids (chlorogenic and p-hydroxycinnamic acids), and tannins. The effects of couch grass extract in the form of a cream on several measures of lipid peroxidation in allergic contact dermatitis were studied in experimental conditions. Cream containing couch grass extract was found to have normalizing actions on measures of lipid peroxidation (diene conjugates, malondialdehyde, catalase) in the plasma of experimental animals.
Keywords: Couch grass; chemical composition; antioxidant properties

Reverse-phase HPLC allowed detection of triglycerides (containing palmitoleic acid radicals) in sea buckthorne oil extracted from the parenchyma of the fruit on the background of the conventional triglycerides used as extractants. This allows rapid verification of the authenticity of the oil and detection of adulteration. Simple replacement of refractometric detection with a spectrophotometric procedure allows the carotenoid composition of the oil to be monitored at the same time.
Keywords: Sea buckthorne oil; HPLC; adulteration; authenticity

Studies of synthesis routes for biologically active 14α-hydroxylated steroids by V. V. Yaderets; V. A. Andryushina; N. E. Voishvillo; T. S. Stytsenko; O. A. Zeinalov (55-58).
The conditions for preparing 14α-hydroxyandrostenedione - an intermediate in the synthesis of highly active gestagens - using the fungus Curvularia lunata CBE with an increased steroid substrate load of 5 g/liter in the presence of methylcyclodextrin were identified. The microbiological method of introducing 14α-hydroxy groups into the androstane structure has significant advantages over chemical approaches from the technical and ecological points of view and for obtaining a higher yield.
Keywords: 14α-Hydroxylated steroids; synthesis methods

Synthesis of biologically active gels for the treatment and prophylaxis of soft tissue and bone damage by N. A. Sabirzyanov; T. G. Khonina; E. A. Bogdanova; S. P. Yatsenko; L. P. Larionov; N. G. Sarkisyan; G. I. Ron’ (59-61).
A method for the synthesis of combined calcium-, phosphorus-, and silicon-containing hydrogels from silicon glycerates was developed, along with methods for preparing glycerohydrogels based on these hydrogels using different types of hydroxyapatite (powder, suspension, colloidal solution) to create pharmaceutical formulations for local and external application with wound-healing and osteoplastic actions.
Keywords: Gels; hydroxyapatites; synthesis; wound-healing and osteoplastic actions

Effects of moisture on the pressing of pharmaceutical powders by N. N. Zhuikova; O. S. Sablina; A. S. Gavrilov (62-64).
The effects of moisture on the rheological and elastic-plastic characteristics of compressible powders and the qualitative characteristics of tablets of aspartame-containing sweetener were studied. Theoretical and experimental studies identified the need for additional stages of moistening tableting material in pressing techniques.
Keywords: Pharmaceutical powders; moisture; pressing

The design, development, and introduction of an economical and reliable apparatus for dosed batching of syrup formulations of pharmaceutical preparations, i.e., gravitational batching unit URG-1, are described. The apparatus is compact and batches syrups with an accuracy meeting the requirements of All-Union Standard OST 64-992–85. The doser can be used in small-scale production facilities.
Keywords: Gravitational unit; batching

The effects of tableting with potassium bromide on the infrared absorption spectra of indomethacin by A. P. Fedotov; T. P. Shakhtshneider; Yu. A. Chesalov; E. V. Surov (68-70).
The effects of tableting with KBr on the IR absorption spectra of molecular crystals were studied at room temperature. Study substances were mechanically activated mixtures of crystalline indomethacin and the excipient polyethylene glycol at ratios of 1:1 and 1:3. There was a marked widening of absorption bands in the range 2000–500 cm−1 in the IR spectra of mechanically activated mixtures in tablets with KBr. These experimental results are assessed within the framework of possible interactions between study samples and the KBr matrix during tableting and storage as powered mixtures.
Keywords: Indomethacin; IR spectra; potassium bromide; tableting