Pharmaceutical Chemistry Journal (v.42, #2)

The new antitumor agent morfozol: Intracellular distribution and effects on DNA synthesis by P. B. Gorbacheva; A. G. Tikhomirov; L. Yu. Dederer; N. A. Ivanova; O. S. Erofeeva; L. I. Ochertyanova; I. A. Efimenko (53-55).
In vitro studies of the interaction of DNA with morfozol (a palladium (II) acid complex) demonstrated active binding with DNA, detected in terms of reductions in accessibility to actinomycin D. Extensive and stable inhibition of DNA synthesis was seen in L1210 and P388 leukemia cells; this was less marked in Akatol and B16 melanoma cells. Studies of the intracellular distribution of palladium in Akatol and P388 tumors after administration of Morfozol to tumor-bearing mice showed predominant accumulation in the cytosol fraction, which is evidence of an active interaction of the agent with cell proteins. I.p. administration of morfozol led to quite high palladium concentrations in the nuclear fraction. As morfozol is characterized by high reactivity, there are probably other targets, such as DNA polymerase and regulatory protein factors.

Synthesis and antitumor properties of new spiro(benzo[h]quinazoline-7,1′-cyclohexane) derivatives by I. I. Markosyan; S. A. Gabrielyan; G. A. Panosyan; F. G. Arsenyan; B. T. Garibdzhanyan (56-59).
4-Amino-3-cyano-1,2-dihydrospiro(naphathaline-2,1′-cyclohexane) (aminonitrile) was converted by interaction with p-tolyl acid chloranhydride into 4-(4-methylbenzoyl)amino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (II), which was subjected to cyclization to form 2-(p-tolyl)-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane) (III). This aminonitrile was converted, using a known method, to 4-ethoxymethyleneimino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (IV). Compound IV was condensed with hydrazides of aromatic, alkylaromatic, and alkoxyaromatic acids in dimethylformamide, producing 5-substituted 7,8-dihydrospiro(benzo[h]triazolo[2,3-c]quinazolines) (Va-v) at high yield. The antitumor properties of the resulting compounds were studied using two models of grafted mouse tumors-Ehrlich ascites carcinoma (EAC) and sarcoma 180. Anumber of the newly synthesized compounds had, along with moderate acute toxicity, marked antitumor activity in experimental conditions.

Synthesis and properties of dipyrimido-[4,5-b][5,4-f]-1,4-thiazepine derivatives by T. S. Safonova; M. P. Nemeryuk; N. A. Grineva; M. M. Likhovidova; A. F. Keremov (60-63).
Derivatives of dipyrimido[4,5-b][5,4-f]-1,4-thiazepine were synthesized and some of their properties were studied.

Synthesis and anti-HIV activity of triterpene conjugates of α-d-glucosamine by L. A. Baltina Jr.; R. M. Kondratenko; O. A. Plyasunova; L. A. Baltina; A. G. Pokrovskii; L. M. Khalilov; F. Z. Galin; G. A. Tolstikov (64-67).
This report describes new triterpene conjugates of α-D-glucosamine, i.e. modified glycyrrhizic acid (GA) analogs containing 18,19-dehydroglycyrrhetic acid 3-O-hemisuccinate and maleate and 11-deoxyglycyrrhetic acid 3-O-hemiphthalate fragments synthesized using N,N′-dicyclohexylcarbodiimide-N-hydroxybenzotriazole. 3-O-[3-(N-2-deoxy-α-D-glucopyranos-2-yl)-carbamoyl]-phthaloyl-11-deoxyglycyrrhetic acid was found to have marked anti-HIV activity (the CD50 (50% cytotoxic concentration) was 150 µg/ml, the ID50 (50% effective concentration) was 1.5 µg/ml, and the index of selectivity (IS, IC50/ID50) was 100) andwas more active than GA in terms of IS (IS = 9.6).

Synthesis of 1-aroylmethyl-and 1-aryloxymethyl-3,4-dihydroisoquinolines and their effects on blood clotting by A. G. Mikhailovksii; N. N. Polygalova; E. S. Limanskii; N. G. Ismailova; B. Ya. Syropyatov; M. I. Vakhrin (68-71).
Acylation of a number of tertiary enamines with aroylchlorides was used to synthesize 1-aroylmethyl-3,4-dihydroisoquinolines. Reaction of 1-chloromethyl-3,3-dimethyl-3,4-dihydroisoquinoline with phenols with interphase catalysis was also used to make 1-aryloxymethyl-3,4-dihydroisoquinoline derivatives. 1-Aroylmethylisoquinolines characteristically had a hemostatic effect, while 1-aryloxymethyl-3,4-dihydroisoquinolines had an anticoagulant effect. The most active compound increased blood clotting by 17.7%.

Antagonists of AMPA/KA and NMDA (glycine site) glutamate receptors by M. G. Kadieva; É. T. Oganesyan; O. H. Zefirova (72-80).
The present review systematizes studies of recent years on the structure-activity relationship of antagonists of the glycine site of NMDA-type glutamate receptors and antagonists of AMPA-kainate-type glutamate receptors. Extreme activation of ionotropic glutamate receptors is known to promote the development of a number of socially important diseases, such as Alzheimer's disease and Parkinson's disease. Construction of inhibitors of these receptors is therefore one of the major directions in contemporary medicinal chemistry. This review may be useful for specialists engaged in the development of new pharmacologically active substances.

Biological characteristics and useful properties of tarragon (Artemisia dracunculus L.) (review) by A. M. Aglarova; I. N. Zilfikarov; O. V. Severtseva (81-86).
This review systematizes published data on the chemical composition, biological activities, and uses of the above-ground part of tarragon (Artemisia dracunculus L., Asteraceae family). Analysis of the pharmacological properties of tarragon showed that the most interesting items from the medicinal point of view were its abilities to influence brain function and gastrointestinal tract function and the presence of a broad spectrum of antimicrobial activity. The complexity and variety of the chemical composition of tarragon generates the needs to identify the main groups of biologically active substances, to specify the main measures of quality and raw material standardization methods, and to perform further pharmacological studies with the aim of developing new tarragon-based medicinal agents.

Studies of Physalis alkekengi L. fruits as a source of xanthophylls by V. I. Deineka; V. N. Sorokopudov; L. A. Deineka; M. Yu. Tret’yakov; V. V. Fesenko (87-88).
The studies reported here established that fruits of the perennial and quite hardy plant Physalis alkekengi grown in the conditions of the Belgorod area accumulate zeaxanthin (and β-cryptoxanthin) derivatives at levels of up to 20 mg/g of husks, which are needed for the prevention of age-related visual loss. Furthermore, attention is drawn to the berries of this Physalis species, which can be used in foods as a source of zeaxanthin (about 0.30 mg per berry).

This article presents methodological approaches to the development of tablet formulations of medicinal agents by direct pressing. Using a number of preparations as examples, the principles underlying the selection of technologies and choice of excipients for direct pressing are presented. Contemporary highly effective excipients used in direct pressing technology for modification of the technical characteristics of tabletting mixtures are reviewed.

Applications of extraction freezing in pharmacology and biochemistry by V. N. Bekhterev; S. N. Gavrilova; E. V. Koshkareva (95-97).
A method for extracting organic substances from aqueous media by combining extraction with freezing is described. The method allows hydrophilic extractants to be used. Analysis of ionogenic organic compounds provides an example demonstrating the wide potential of this method. A method for the analysis of 1,4-benzodiazepines in urine was developed. As compared with existing methods, the sample preparation procedure described here is significantly quicker and simpler, and requires virtually no laboratory equipment.

Quantitative estimation of benzylisoquinoline derivatives by coulometric titration by G. K. Ziyatdinova; A. I. Samigullin; S. G. Abdullina; G. K. Budnikov (98-101).
A method for estimating papaverine HCl and drotaverine HCl by coulometric titration with biamperometric indication of the end point was developed. The stoichiometric coefficients of the reactions of papaverine and drotaverine with electrogenerated chlorine were determined. Microgram quantities of agents in substance and therapeutic forms were estimated with a relative standard deviation (RSD) of 0.01–0.03.

Estimation of catecholamines in daily urine by stripping voltammetry by A. M. Gusakova; E. A. Ivanovskaya (102-104).
A voltammetric method for the quantitative estimation of adrenaline (A) and noradrenaline (NA) in daily urine was developed using a carbon glass electrode. The lower detection limits for A and NA concentrations were 1 × 10−9 g/ml. The relative standard deviation for the range of concentrations 1 × 10−9 to 1 × 10−5 M was no greater than 0.1.