The aim of this work is to create new modified dosage forms of amiodarone with triterpene glycosides in various stoichiometric ratios and to study their cytotoxicity on HeLa cells. Complexes of glycyrrhizic acid (GA) and the monoammonium salt of glycyrrhizic acid (MASGA) with amiodarone hydrochloride were obtained, characterized by certain physicochemical parameters, and studied by IR and UV spectroscopy. The supramolecular complexes were formed mainly through weak intermolecular interactions such as hydrogen bonding and ion-dipole, electrostatic, and dipole-dipole interactions. The quantitative content of GA and MASGA in the complexes was shown to affect the cytotoxicity of the drug. A modified form of amiodarone may be developed in future research and could become a promising antiarrhythmic drug.

Получен ряд супрамолекулярных комплексов моноаммонийной соли глицирризиновой кислоты (моноаммония глицирризинат, MG) с низкомолекулярными биологически активными соединениями: с аминокислотами — аргинин (Arg), метионин (Met), триптофан (Trp), цистеин (Cys), DL-карнитин·HCl (Car); с фенольными соединениями — кверцетин (Que), рутин (Rut), коричная (CinA), метоксикоричная (MethA) и феруловая (FA) кислоты. Проведено изучение антиоксидантной (AOA) in vitro и гепатопротекторной (ГПА) in vivo активности новых соединений в эксперименте. При исследовании AOA аминокислот и полифенолов показана наибольшая активность для Rut, Que и MethA. Комплексообразование изученных антиоксидантов приводит к увеличению AOA соединений в 1,5 – 6,5 раз (p < 0,05). Наиболее активными по AOA оказались комплексы MG с MethA, Car и Met. При внутрижелудочном ведении в дозе 5 мг/кг мышам с CCl4-индуцированным гепатитом высокую степень ГПА проявили комплексы MG/MethA, MG/Met и MG/Que, среднюю степень — MG/Rut, MG/Car и MG/FA. Введение комплексов MG/Car и MG/Cys приводит к снижению весовых коэффициентов печени в среднем на 35 и 30 % соответственно (p < 0,05 относительно контрольных значений). Наиболее активными по изученным параметрам оказались комплексы моноаммония глицирризината с MethA, Met, Que, Car и Cys, перспективные для дальнейшего исследования.

We studied the effects of glycyrrhetinic acid (bioactive aglycone of glycyrrhizin) and its ester derivatives at positions C-3 and C-30 on the cell volume regulation in rat thymocytes under conditions of hypoosmotic stress. Native glycyrrhetinic acid completely suppressed this process with half-maximal concentration of 12.7±1.4 μM and Hill coefficient of 3.1±0.6. Formation of esters at C-3 (esters with the acetic, cinnamic and methoxi-cinnamic acid) and at C-30 (methyl ester) drastically decreased the inhibitory activity of the molecule, suggesting that intact hydroxyl group at C-3 and carboxyl group at C-30 are structurally important determinants of biological activity of glycyrrhetinic acid towards volume regulation of thymic lymphocytes.

A series of new 3-O-acetyl-18β -H-glycyrrhetic acid amides with S-containing heterocyclic amines (2-aminothiadiazole; 2-amino-5-methyl-, ethyl-, propyl-, and isobutylthiadiazole; 2-aminothiazole) were synthesized. The structures of the new amides were established using UV, IR, PMR, and 13C NMR spectroscopy and mass spectrometry.

Two new benzazepine alkaloids (1 and 2) were isolated from the whole plants of Thalictrum wangii. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1 and 2 were tested for their anti-rotavirus activity. The results revealed that compounds 1 and 2 exhibited potent anti-rotavirus activity with TI values of 17.9 and 17.6, respectively.

Supramolecular complexes of glycyrrhizic acid (GA) and salicylic acid (SA) in various mole ratios of 1:1, 2:1, 4:1, and 8:1 were prepared for the first time. Their IR and UV spectra indicated that a complex with SA did form. The supramolecular complex with a 2:1 ratio, which was called DAG-1, had the optimal molecular ratio of GA and SA for high biological activity. DAG-1 at a concentration of 10–7 M induced antioxidantenzyme (catalase, peroxidase, superoxide dismutase) activity and stimulated cotton growth and development under model chloride salinity conditions.

The synthesis has been effected of alkyl anabasinoprop-2-yl and alkyl piperidinoprop-2-yl methylphosphonothionates. It has been shown by1H,13C and31P NMR spectroscopies that the anabasine derivatives exist in solution as four diastereomeric forms. The kinetics of the interaction of the compounds synthesized with two types of cholinesterases has been studied.

Results on the study over the last 20 years of the relationship between the structure of derivatives of the alkaloid anabasine and their cholinotropic activity are generalized.

A series of new phosphorylated esters of anabasine, lupinine, and piperidine differing by the nature of the alkyl radicals attached to the phosphorus atom has been synthesized. The results of investigations of the antiesterase properties of the compounds in relation to the acetylcholinesterase of human blood erythrocytes and of the turnip moth and the carboxylesterase of porcine kidney have shown a selectivity of their action in relation to the insect enzyme and a substantially lower activity towards esterases of warm-blooded animals.

The effect of ionic strength was used to analyze the mechanism of reversible acetylcholinesterase inhibition by three alkoxymethylthionphosphonates. The most considerable realization of the hydrophobic interaction with the surroundings of the enzyme esteratic site was marked for n-butyl derivative (compound I). The replacement of piperidine by morpholine (compound II) resulted in a decrease of the anticholinesterase activity by an order due to enhancement of the inhibitor hydrophilicity. An increase of MgCl2 concentration promotes an enhancement of the uncompetitive component contribution for compound III contrast to compound II. Hydrophobicity of the phosphoryl part of the compound I molecule is balanced under hydrophobic interaction of the heterocyclic "cationic head" with the enzyme anionic site. The break of this equilibrium intensifies the allosteric regulation, on the one hand, and lowers the inhibitor efficiency, on the other hand.

The work was based on the interrelationship of the diastereomeric anisochromicity on the introduction of an asymmetric center outside the ring of the amino alcohol and the anticholinesterase activity of the compounds including a morpholine heterocycle. A method is described for obtaining the compounds presented. Physicochemical constants and a method of determining anticholinesterase activity are given. In the series of O-ethyl derivatives of these compounds significant activity with respect to acetylcholinesterase can be distinguished. The efficiency of the series tested is comparable with that of tetraalkylammonium salts. It has been shown that alkyl 1-methyl-2-morpholinoethyl methylphosphonothionates are present in solution in two optically isomeric forms in a ratio of 1:3.

AbstractThe title compounds (III) are prepared from the thiophosphonic chlorides (I) and the hydroxyethylpiperidine (II).

Some O-alkyl-O-[N-(β-hydroxyethyl)piperidyl]alkylthiophosphonates have been synthesized, and shown to be powerful reversible inhibitors of acetylcholinesterase and butyrylcholinesterase.

Some esters of O-alkyl methylphosphonic acid and thioesters of O-alkyl methylthiophosphonic acid derived from the alkaloids lupinine and epilupinine have been prepared. These were found to be reversible competitive inhibitors of acetylcholinesterase and butyrylcholinesterase.

Anabasine derivatives based on methylphosphonothoic acid have been synthesized. It has been shown by PMR spectroscopy that in solution O-alkyl O-[β-(anabasin-1-yl)ethyl] methylphosphonothioates exist in two stereomeric forms, which is due to the influence of the optically active anabasine residue. It has been shown that these compounds are competitive reversible inhibitors of acetylcholinesterase and of butyrylcholinesterase.

ChemInformVolume 18, Issue 42 Natural Products ChemInform Abstract: Synthesis of Some Organo-Phosphorus Derivatives of Lupinine and Epilupinine and Their Interaction with Cholinesterases. D. N. DALIMOV, D. N. DALIMOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorM. B. GAFUROV, M. B. GAFUROV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorG. M. VAIZBURG, G. M. VAIZBURG Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorA. A. AGDUVAKHABOV, A. A. AGDUVAKHABOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorN. N. GODOVIKOV, N. N. GODOVIKOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this author D. N. DALIMOV, D. N. DALIMOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorM. B. GAFUROV, M. B. GAFUROV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorG. M. VAIZBURG, G. M. VAIZBURG Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorA. A. AGDUVAKHABOV, A. A. AGDUVAKHABOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this authorN. N. GODOVIKOV, N. N. GODOVIKOV Inst. bioorg. khim. AN Uzbek. SSR, TashkentSearch for more papers by this author First published: October 20, 1987 https://doi.org/10.1002/chin.198742324Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue42October 20, 1987 RelatedInformation