scholarly journals CYCLODEXTRIN INCLUSION COMPLEXES OF PHARMACEUTICALLY ACTIVE DERIVATIVES OF THE CYTISINE ALKALOID AND THEIR HEMORHEOLOGICAL ACTIVITY

2021 ◽  
pp. 72-87
Author(s):  
G.K. Mukusheva ◽  
◽  
A.R. Zhasymbekova ◽  
Z.B. Satpaeva ◽  
Е.V. Minayeva ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Chemical Shifts ◽  
Differential Scanning Calorimetric ◽  
Supramolecular System ◽  
Alkaloid Cytisine ◽  
Two Samples ◽  
Cyclodextrin Cavity ◽  
Cytisine Alkaloid ◽  
Derivatives Of

The alkaloid cytisine is of great importance for modern pharmacological studies. This alkaloid can be used as a component of the supramolecular system with cyclic oligosaccharides, namely β-cyclodextrins, which have a truncated cone-shaped molecule with internal protons Н3 and Н5 and external ones Н2 and Н4. The aim of the work is to obtain inclusion complexes of pharmaceutically active derivatives of the alkaloid cytisine. The inclusion complexes of cytisine alkaloid derivatives with β-CD and 2-HP-β-CD were obtained by the coprecipitation method. Thermogravimetric, differential thermal, and differential scanning calorimetric analyzes were performed. It was shown that inclusion complexes of substrate with cyclodextrin cavity of receptors were formed. The greatest change in the chemical shifts of protons during the formation of supra-molecular complexes occurs with the internal protons H-3 and H-5 of the cyclodextrin cavity. All calculated values are in good agreement with experimental data. The prepa-ration of supramolecular complexes has been proven using a variety of physicochemical methods of analysis. According to DSC data, the process of complexes destruction in the temperature range of 30-610°C was studied in comparison with the data of the initial cyclodextrin. The hemorheological effects of the investigated samples were studied in vitro. Among four samples studied, two samples showed the ability to reduce blood viscosity in vitro in the blood hyperviscosity model.

Heteroassociation of meso-sulfonatophenylporphyrins with β- and γ-cyclodextrin

2001 ◽  
Vol 05 (05) ◽  
pp. 465-473 ◽  
Author(s):  
ZOUBIR EL-HACHEMI ◽  
JOAN-ANTON FARRERA ◽  
HECTOR GARCÍA-ORTEGA ◽  
OSCAR RAMÍREZ-GUTÍERREZ ◽  
JOSEP M. RIBÓ
Keyword(s):  
Inclusion Complexes ◽  
Bulk Water ◽  
Hydrophobic Region ◽  
Water Solutions ◽  
H Nmr ◽  
Cyclodextrin Inclusion Complexes ◽  
Cyclodextrin Inclusion ◽  
Cyclodextrin Cavity ◽  
Nuclear Overhauser ◽  
Derivatives Of

The effect of the addition of β- and γ-cyclodextrin (β-CD, γ-CD) to water solutions ( D 2 O ) of the 4'-sulfonato derivatives of meso-tetraphenylporphyrin (TPPS4, TPPS3, TPPS2o and TPPS2a) was studied by 1 H NMR at several temperatures. In all cases the disaggregation of the porphyrin homoassociates was detected, although in most cases it was only partial. Nuclear Overhauser signals (ROESY) show that cyclodextrin inclusion complexes were formed with TPPS4, TPPS3, and TPPS2o, but not with TPPS2a. These complexes include the sulfonatophenyl groups as guest, but not the hydrophobic phenyl substituents. The geometry of the complexes corresponds to that in which the sulfonatophenyl substituent is introduced through the secondary face of β-CD and through the primary face of γ-CD. In the inclusion complexes the polar sulfonato group is inside the cyclodextrin cavity but near to the hydrophilic interface with the bulk water. This explains the absence of complexation in the case of cationic porphyrins such as 5,10,15,20-tetrakis(N-methylpyridin-4-yl)porphyrin (TMPyP), and the decrease in the solubility when the β-CD complex of 5,15-bis(4-sulfonatophenyl)porphyrin (DPPS2o) forms. Complexes of the cyclodextrins with porphyrin homoassociates were also detected. This indicates that the heteroassociation avoids the formation of staggered stacks of porphyrin homoassociates, but has less effect on the association through the hydrophobic region of the phenyl substituents. This last type of aggregation, which is not significantly affected by the addition of α-CD, explains why the hydrophobic phenyl substituents are not complexed by the cyclodextrins.

scholarly journals Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1609
Author(s):  
Víctor González-Ruiz ◽  
Ángel Cores ◽  
Olmo Martín-Cámara ◽  
Karen Orellana ◽  
Víctor Cervera-Carrascón ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Topoisomerase I ◽  
Chemical Shifts ◽  
Resonance Spectroscopy ◽  
Human Neuroblastoma ◽  
Anti Cancer ◽  
Pharmacokinetic Properties ◽  
Cyclodextrin Cavity ◽  
Luotonin A ◽  
Phase Liquid

The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.

scholarly journals HYDRAZIDE OF o-HYDROXYBENZOIC ACID AND ITS DERIVATIVES. SYNTHESIS AND PROPERTIES

2020 ◽  
Vol 1 (383) ◽  
pp. 14-25
Author(s):  
О. А. Nurkenov ◽  
S. D. Fazylov ◽  
M. Zh. Zhurinov ◽  
Zh. B. Satpaeva ◽  
М. Zh. Burkeev ◽  
...  
Keyword(s):  
Chemical Shifts ◽  
Condensation Reaction ◽  
13C Nmr Spectroscopy ◽  
Hydroxybenzoic Acid ◽  
Monocytic Cell ◽  
Integrated Intensity ◽  
Human Monocytic Cell ◽  
Thiosemicarbazide Derivatives ◽  
Derivatives Of

The article presents the results of a study by the authors of the article on the development of new ways of synthesis and study of the biological activity of hydrazide derivatives of o-hydroxybenzoic acid. Methods for the preparation of hydrazone, oxadiazole, thiosemicarbazide, 1,2,4-triazole-3-thionic derivatives and methods for their further modification are described. The condensation reaction of hydroxybenzoic acid hydrazides with 1-deoxy-2,3,4,6-tetra-O-acetyl-D-glucopyranosyl isothiocyanate synthesized their corresponding acetylated glycosyl-contai-ning thiosemicarbazide derivatives. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy, as well as by the data of two-dimensional spectra of COSY (1H-1H) and HMQC (1H-13C). The values of chemical shifts, multiplicity, and integrated intensity of 1H and 13C signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (1Н-1Н) and HMQC (1Н-13С), homo- and heteronuclear interactions were established, confirming the structure of the compounds under study. The results of evaluating their antimicrobial, anti-inflammatory and cytotoxic activity (in vitro) on cultures of human monocytic cell lines MonoMac-6 and THP-1Blue are described.

SOME DIRECTIONS IN THE MODIFICATION OF AZOLES

2020 ◽  
Vol 5 (443) ◽  
pp. 85-91
Author(s):  
Ibrayev M.K., ◽  
◽  
Takibayeva A.T., ◽  
Fazylov S.D., ◽  
Rakhimberlinova Zh.B., ◽  
...  
Keyword(s):  
13C Nmr Spectroscopy ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Synthesis Conditions ◽  
Alkaloid Cytisine ◽  
Azole Ring ◽  
Cyclic Compounds ◽  
New Compounds ◽  
Derivatives Of

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.

Complexation with Hydroxypropyl-gama-Cyclodextrin of Birch Tree Extract Physico-chemical Characterisation of their Binary Products

2008 ◽  
Vol 59 (6) ◽  
Author(s):  
Codruta Soica ◽  
Cristina A. Dehelean ◽  
Valentin Ordodi ◽  
Diana Antal ◽  
Vicentiu Vlaia
Keyword(s):  
Inclusion Complexes ◽  
Water Solubility ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Bark Extract ◽  
Birch Bark ◽  
Preparation Methods ◽  
Birch Tree ◽  
Physico Chemical

Birch bark contains important pentacyclic triterpens that determine an anticancer, anti-inflammatory and antiviral activity. The compounds can be extracted by simple procedures with organic solvents. The major problem of this type of triterpens is their low water solubility which can be increased by physical procedures like cyclodextrin complexation. The aim of present study was to analyse the products between birch bark extract and hydroxypropyl-g -cyclodextrin. Hydroxypropyl-g -cyclodextrin (HPGCD) was used as a host to improve its solubility in water, via inclusion complex formation. In order to obtain the inclusion complexes, 1:2 molar ratio and two preparation methods (physical mixing, kneading) were used. The inclusion complexes were analyzed by in vitro dissolution tests, thermal analysis and X-ray diffraction.

Synthesis and Evaluation of Aromatic Surfactants as Potential Antibacterial and Cytotoxic Agents

2019 ◽  
Vol 16 (6) ◽  
pp. 478-484
Author(s):  
Kenia Barrantes ◽  
Mary Fuentes ◽  
Luz Chacón ◽  
Rosario Achí ◽  
Jorge Granados-Zuñiga ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Hela Cells ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Hydroxybenzoic Acid ◽  
Derivatives Of

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives

2019 ◽  
Vol 16 (12) ◽  
pp. 1360-1369 ◽  
Author(s):  
Rail Khaziev ◽  
Nikita Shtyrlin ◽  
Roman Pavelyev ◽  
Raushan Nigmatullin ◽  
Raylya Gabbasova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid Membranes ◽  
Specific Activity ◽  
Tuberculosis H37rv ◽  
Microbial Pathogens ◽  
Adamantane Derivatives ◽  
Carbon Cage ◽  
H37rv Strain ◽  
Derivatives Of

Background: Adamantane derivatives possess multiple pharmacological activities such as antiviral, anticancer, antimycobacterial, antidiabetic, antiparkinsonian and others. The interest of medicinal chemists in adamantane compounds is due to their unique spatial structure, high lipophilicity, and carbon cage rigidity. As a result, these molecules can easily penetrate biological lipid membranes and often have unique target-specific activity profile. Another pharmacophore studied in this work is pyridoxine (vitamin B6). Pyridoxine plays highly important roles in living cells as a key cofactor of many enzymes. On the other hand, its molecular scaffold is a valuable structural platform which has led to the development of several launched drugs (Pyritinol, Pirisudanol, Cycletanine, Mangafodipir) and a wide number of preclinical and clinical drug candidates. Objective: The objective of this study is a synthesis of pyridoxine-adamantane and pyridoxinecyclooctane dipharmacophore molecules. The underlying idea was to assess the antibacterial and antiviral potential of such dipharmacophores, based on multiple examples of promising antiinfective agents which have in their structures adamantane and pyridoxine moieties. Another specific reason was to explore the ability of pyridoxine pharmacophore to suppress the potential of microbial pathogens to develop resistance to drug molecules. Methods: In this study, a series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkyl amines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. All synthesized compounds have been tested for their in vitro activity against M. tuberculosis H37Rv strain and H3N2 (A/Aichi/2/68) influenza virus. Results: Series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkylamines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. Reaction of cycloalkylamines with pyridoxine derivatives, in which meta-hydroxyl and ortho-hydroxymethyl groups are protected by acetyl groups, represents a useful alternative to reductive amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza virus (EC50 52-88 µg/mL) that was comparable to the activity of Amantadine, though lower than the activity of Rimantadine. The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane. Conclusion: The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane.

Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

2020 ◽  
Vol 16 ◽  
Author(s):  
Lucas da Silva Santos ◽  
Matheus Fillipe Langanke de Carvalho ◽  
Ana Claudia de Souza Pinto ◽  
Amanda Luisa da Fonseca ◽  
Julio César Dias Lopes ◽  
...  
Keyword(s):  
Triazole Ring ◽  
Antiplasmodial Activity ◽  
World Health ◽  
Dipolar Cycloaddition ◽  
Terminal Alkynes ◽  
The World ◽  
Ic50 Values ◽  
Derivatives Of ◽  
Active Substances

Background: Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs. Objective: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins and a 3,4- dihydroisocoumarin. Method: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4-dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). Results: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively.

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