Pharmaceutical Chemistry Journal (v.41, #6)

Immunoglobulin: DNA cofactor interaction by M. K. Malinka; V. M. Petriev; V. K. Podgorodnichenko (289-293).
The reasons for the appearance of DNA-binding activity of immunoglobulins (Ig) after chromatography on anion-exchange Sephadexes were studied. Elution of Ig from these Sephadexes with 0.5 M NaCl was found, using an orcinol method, to be associated with degradation of the matrix, with the appearance of water-soluble fragments (WSF) of Sephadex in the eluate. Degradation of the Sephadex matrix also occurred on washing of unloaded Sephadex. Monoclonal antibodies which did not initially interact with DNA acquired the ability to react with DNA after incubation with Sephadex WSF, as demonstrated using immunoenzyme analysis. It is suggested that the WSF forming on passage of Ig through anion exchange Sephadex columns interact with Ig to generate cations which can react with negatively charged antigens and, particularly DNA.

Pharmacokinetics of various Russian therapeutic formulations by S. N. Ptitsina; V. I. Bobrov; M. M. Borisov (294-296).
The pharmacokinetics of various therapeutic forms of azithromycin of Russian origin (suspension, tablets, capsules) after oral administration to rabbits were studied using a microbiological agar diffusion method with the test microbe Micrococcus luteus. These studies showed that the maximal azithromycin concentrations seen on analysis of the three formulations were reached at 1–2 h and that the elimination halflives were 2–3.7 h.

A diglyceride derivative of methotrexate: Synthesis and cytotoxic activity in addressed liposomes by E. L. Vodovozova; G. P. Gaenko; E. S. Bobrikova; G. V. Pazynina; Yu. G. Molotkovskii (297-301).
A synthesis of a lipophilic derivative of methotrexate was devised, this being suitable for insertion into the membranes of carrier liposomes. The conjugate consisted of a rac-1,2-dioleoylglycerol residue attached via an ester bond to methotrexate via the β-alanyl-N-carbonylmethylene linker. A liposomal formulation of the derivative showed cytotoxic activity in cultures of M3 melanoma cells; this activity depended on the structure of the carbohydrate ligands on the liposome surface. As compared with a control liposome preparation carrying a diglyceride derivative of methotrexate and bearing an inactive pentaol aminoglucitol ligand, the cytotoxicity of liposomes carrying trisaccharide A residues was 1.5 times greater and that of liposome carrying tetrasaccharide sialyl-Lewis X was three times greater.

Synthesis and anticonvulsant evaluation of semicarbazones of acetophenone Mannich bases by A. S. Raja; S. N. Pandeya; S. S. Panda; J. P. Stables (302-307).
Several semicarbazones of acetophenone and p-chloroacetophenone Mannich bases were designed and synthesized to meet the pharmacophore requirements essential for anticonvulsant activity. Mannich bases of acetophenone and p-chloroacetophenone were prepared by reacting formaldehyde with various secondary amines and then condensed with several aryl semicarbazides to yield the corresponding semicarbazones. All compounds were evaluated for their anticonvulsant activity by maximal electroshock (MES) and by subcutaneous metrazole (ScMet) and strychnine (ScSty) induced seizure methods, and their neurotoxic effects were determined using the rotorod test. The title compounds were also investigated for antidepressant and sedative-hypnotic potentiation properties. It is established that 3-[3-chlorophenyl(β-dimethylaminopropiophenone)semicarbazone] has excellent anticonvulsant activity in MES, ScSty, and ScMet tests and exhibits a potent antidepressant effect in the absence of sedative-hypnotic potentiation. The present study has proved our earlier hypothesis concerning the pharmacophore model with essential binding sites for semicarbazones. The inclusion of an additional moiety (CH2-CH2-N<) at the electron donor acceptor group retained the anticonvulsant activity.

3-Aminomethyl-substituted thiazolo[3,2-a]benzimidazoles were synthesized by reacting 3-(chloromethyl) thiazolo[3,2-a]benzimidazole with primary and secondary amines. The resulting 3-amino-derivatives of thiazolobenzimidazole were tested in vitro for antioxidant properties in relation to the autooxidation of adrenaline to adrenochrome. All the compounds studied inhibited, to different extents, the oxidation of adrenaline to adrenochrome, thus preventing formation of the superoxide radical.

Steroid nitrates. II. Synthesis and hormonal activity of 9α,11β-dihydroxyestra-1,3,5(10)-triene 11-nitrates by V. M. Rzheznikov; L. E. Golubovskaya; O. N. Minailova; T. I. Ivanenko; V. P. Fedotov (310-313).
11-Nitrates of 9α,11β-dihydroxy derivatives of estrone, estradiol, and ethinylestradiol were synthesized by oxidative nitration of the corresponding estratriene 3-acetates with cerium ammonium nitrate. Three methods are given for this reaction. Compounds had high antifertility and estrogen activity. Antifertility actions were much greater than their estrogen activities, as compared with the similar levels seen with ethinylestradiol.

Reactions of the polyene macrolide antibiotic mycoheptin with aldehydes and hypophosphorous acid yielded its hydrophosphoryl derivatives. The physicochemical and biological properties the resulting mycoheptin derivatives were studied. Biological investigations showed that hydrophosphoryl derivatives of mycoheptin were less toxic than the initial antibiotic and had antifungal and antiviral activity.

Synthesis and antimicrobial activity of substituted tetrahydroindazoles and cyclohexanones by V. L. Gein; A. A. Zorina; I. V. Nosova; É. V. Voronina; M. I. Vakhrin; A. I. Kriven’ko (319-322).
2,4-Dibenzyloxy(diallyloxy)carbonylcyclohexanones (I–XIV) were reacted with hydrazine hydrate via the 1,3-dioxo fragment to form tetrahydroindazoles (XV–XXVIII). Interaction of β-cycloketols (I–XIV) with phenylhydrazine in all cases led to the formation of phenylhydrazones (XXIX–XXXVI). The structures of compounds XV–XXVI were confirmed by IR and 1H NMR spectroscopy. Results obtained from studies of the antimicrobial activity of the compounds synthesized are presented.

Search for the optimal conditions for the distillation of the antibacterial agent glyciphon by I. V. Berdnik; A. A. Muslinkin; I. M. Magdeev (323-326).
Preparation of the high-boiling-point organophosphate antiblastoma agent glyciphon at maximal yield and purity was addressed at the experimental production stage by studying its vacuum distillation by mathematical modeling. The optimum conditions for performing this final stage of the technical process allowed the number of distillations to be decreased and the yield of pharmacological purity product to be increased by an average of 20%.

The effect of various penetration enhancers on the permeation of dexchlorpheniramine maleate from a 2 wt% aqueous phase and from water-oil emulsions (creams) was studied using a modified Franz diffusion cell. A polyamide membrane filter (modeling a biomembrane) was impregnated with n-octanol, sandwiched between two dialysis membranes, and placed between the source and receiver compartments. The permeation coefficient in the aqueous phase was 270 times greater than that in the cream, while the lag time was 3.5 times longer in the cream. A mixture of isopropyl myristate and ethanol (8: 2) gave the highest enhancement ratio, while oleic acid acted as a penetration retardant in the cream formulation.

Effects of colloidal-chemical properties of activated charcoals on their therapeutic efficacy by T. N. Nevar; T. A. Savitskaya; A. V. Osipova; S. E. Makarevich; N. G. Tsigankova; D. D. Grinshpan (332-336).
We report studies addressing the colloidal-chemical properties (stability, rheology, adsorption of model substances) of suspensions of fibrous activated charcoal tablets in which polymer binders were starch and a new water-soluble cellulose derivative. Medical use of charcoal tablets based on the new binder was shown to be effective.

Estimation of vitamin E in plant oils by microcalorimetry by N. V. Sizova; N. Yu. Andreeva (337-340).
Microcalorimetric studies were performed to estimate the content of vitamin E (tocopherols) in natural plant oils. The approach used was a kinetic method of estimating vitamin E and was based on the ability of tocopherols to inhibit a liquid-phase free-radical oxidation reaction. A model reaction consisting of the initiation of cumene (isopropylbenzene) oxidation showed that fatty oils inhibit the free-radical reaction with an induction period proportional to the content of tocopherols in oils. Tocopherol contents measured here were in good agreement with values reported in the literature. Experimental curves were used to calculate oxidation inhibition rate constants; all the oils tested (cameline seed, wintercress, rapeseed, and cedar) had essentially identical values, at k 7 = (1.4–6.8) × 104 mol/liter · sec.

Estimation of several antidepressants using an amperometric biosensor based on immobilized monoamine oxidase by É. P. Medyantseva; R. M. Varlamova; D. A. Gimaletdinova; A. N. Fattakhova; G. K. Budnikov (341-344).
An amperometric biosensor was developed on the basis of a printed platinum electrode and immobilized monoamine oxidase for detecting antidepressants of various classes. The analytical potential of the electrode was assessed: Petylyl (desipramine) and pyrazidol could be estimated from lower detection limits of 8 × 109 M for Petylyl and 8 × 107 M for pyrazidol. A method for estimating pyrazidol in tablets is described.