Synthesis and structure of N-methyl-1-[(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)phenyl]fullerene-C60-[1,9-c]pyrrolidine

Фазылов, С. Д.; Нуркенов, О. А.; Аринова, А. Е.; Сейлханов, Т. М.; Tuktarov, Airat R.; Khuzin, Artur A.; Bakirova, Ryszhan; Муравлева, Л. Е.

doi:10.1134/s1070363215050072

Cited by 5 publications

(5 citation statements)

References 8 publications

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“…Among the reactions that have been used to obtain highly functionalized fullerene derivatives, one of the most employed is the 1,3-dipolar cycloaddition reaction of azomethine ylides to C 60 , also known as the Prato reaction in fullerenes’ community, which provides stable fulleropyrrolidines as products. By using this methodology it was possible to obtain hybrids where the [60]fullerene is attached to peptides, heterocycles, aromatic compounds, carbohydrates, and steroids …”

Section: Introductionmentioning

confidence: 99%

Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning

et al. 2020

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The reaction of C 60 with pregnen-20-carboxaldehyde, a biologically active synthetic steroid, by using a 1,3-dipolar cycloaddition reaction (Prato's protocol) results in the formation of pyrrolidine rings bearing a new stereogenic center on the C2 of the five-membered ring. The formation of the fullerene-steroid hybrids proceeds with preference for the Re face of the 1,3-dipole, with formation of a diastereomeric mixture in 73:15 ratio. The investigation of the chiroptical properties of these conjugates allowed determining the absolute configuration of the new fulleropyrrolidines. In addition, a thorough spectroscopical study permitted to determine the structure of the two mono-cycloadducts. The electrochemical properties of the new hybrids were also evaluated by cyclic voltammetry, both systems exhibit three quasi-reversible reduction waves which are cathodically shifted in regard to the parent C 60 . Theoretical calculations help supporting the experimental data. A conformational study combining semiempirical methods and density functional theory has predicted the most stable diastereomer. On the basis of this agreement, a possible reaction mechanism is presented. Additionally, a molecular docking simulation has been carried out using the HIV-1 protease as receptor, thus paving the way to study the possible application of these stereoisomers in biomedicine.

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Section: Introductionmentioning

confidence: 99%

Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning

et al. 2020

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“…Currently, among a large number of functionalized C60 fullerene compounds, fulleropyrrolidine derivatives are one of the most intensively studied classes [1][2][3]. The 1,3-dipolar cycloaddition of azomethinilides to fullerene, known as the Prato reaction [4], is one of the most effective ways in obtaining fulleropyrrolidines. Compounds containing the pyrrolidine cycle in common organic compounds have a wide spectrum of biological activity and are part of many drugs of both natural and synthetic origin, for example, proline, atropine.…”

Section: Synthesis Of Properties N-methyl-2-(pyrid-4-yl)-34-fulleropmentioning

confidence: 99%

“…It should be noted that some of the most important aspects of the biological activity of fullerens and its derivatives include the fight against HIV and antibacterial activity, inhibition of enzymes, antitumor therapy, controlled drug delivery, neuroprotective properties, and antioxidant activity. In fullerene synthesis, studies of the synthesis of C60 fullerene derivatives containing new "pharmacophore" groups are of great interest [4][5][6][7][8][9][10][11][12]. In this regard, an interesting "pharmacophore" group is the pyridine cycle, which is pert of about 5% of all known drugs.…”

Section: Synthesis Of Properties N-methyl-2-(pyrid-4-yl)-34-fulleropmentioning

confidence: 99%

Synthesis of Properties N-Methyl-2-(Pyrid-4-Yl)-3,4-Fulleropyrrolidine

Фазылов¹,

Нуркенов²,

Аринова

et al. 2020

Series Chemistry and Technology

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The article is devoted to the reactions of [2+3] cycloaddition of pyridine-4-aldehyde to fullerene C60, as well as to the preparation of its water-soluble from of the resulting reaction product N-methyl-2-(pyrid-4-yl)-3,4-fulleropyrrolidine. A literature review of organic compounds containing the pyrrolidine cycle was carried out. It is noted that such compounds have a wide spectrum of biological activity and are part of many drugs of both natural and synthetic origin. In this regard, an interesting “pharmacophore” group is the pyridine cycle, which is part of about 5% of all known drugs. The reaction of pyridin-4-aldehyde with fullerene C60 was carried out in the presence of sarcosine under the conditions of the Prato reaction. The reaction mechanism of 1,2-dipolar cycloaddition, leading to fulleropyrrolidine, is described. The water-soluble complex fulleropyrrolidinas with poly-N-vinylpyrrolidone was obtained. The structures of the synthesized compounds were studied by IR, UV, 1H and 13C NMR spectroscopy, as well as by the date of two-dimensional spectra of COSY (1H-1H) and HMQC (1H-13H). The values of chemical shifts, multiplicity and integrated intensity of 1H and 13C NMR signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (1H-1H) and HMQC (1H-13C) homo- and heteronuclear interaction were established, confirming the structure of the studied compounds. Key words: fullerene C60, sarcosine, pyridine-4-aldehyde, fulleropyrrolidines, Prato reaction, NMR spectra.

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“…The results of a study of a number of compounds on antibacterial and antifungal activity with various test cultures are presented Materials and methods. Synthesis methods and data on the synthesis, structure and physicochemical properties of fulleropyrrolidines (IIa-e) and their tartrate salts are described in [9][10][11][12], are presented in figures 1, 2 and table 1. The antibacterial and antifungal activity of the newly synthesized fulleropyrrolidines (IIa-d) was held at the Department of Microbiology of the Karaganda Medical University.…”

Section: Nas Rk Is Pleased To Announce That Bulletin Of Nas Rk Scientmentioning

confidence: 99%

Indicators of Cell Metabolism in Vitro in Researches of Anti-Inflammatory and Cytotoxic Effects of Fulleropyrrolidines С60 and Their Initial Substrates

Фазылов¹,

Нуркенов²,

Аринова³

et al. 2020

THE NATIONAL ACADEMY OF SCIENCES OF THE REPUBLIC OF KAZAKHSTAN

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The article considers data on the in vitro study of new fulleropyrrolidine compounds for anti-inflammatory and cytotoxic activity in cultures of human monocyte cell lines MonoMac-6 and THP-1Blue and also as inhibitors of human neutrophil elastase. This enzyme is a regulator of inflammation. In different situations, it can act both as a pro-inflammatory and as an anti-inflammatory agent. An imbalance in the regulation of elastase activity plays an important role in the pathogenesis of cystic fibrosis, acute respiratory distress syndrome, bronchiectasis, chronic obstructive pulmonary disease, type 2 diabetes mellitus, atherosclerosis and hypertension. In the future, such studies should lead to the creation of optimal in vitro models that most adequately reflect the situation in vivo and establish the relationship between the structure and activity of the studied drugs. It is noted that the presence of lipophilic properties in fullerene C60 derivatives is especially important in the development of pharmaceuticals for the control of pathogens of various infectious diseases. Fullerene C60 derivatives have the ability to easily penetrate lipid membranes, overcome the blood-brain barrier, and modulate ion transport. Compounds were tested for anti-inflammatory and cytotoxic activity (in vitro) on cultures of human monocytic cell lines MonoMac-6 and THP-1Blue. Modified fullerene compounds of various structures were tested for their inhibitory ability against neutrophil elastase enzyme (in vitro). Elastase activity was evaluated by the ability of fulleropyrrolidine compounds to hydrolyze the synthetic substrate N-methylsuccinyl-Ala-Ala-Pro-Val-7-amino-4-me-thylcoumarin (Calbiochem). The results of studies of fullerene compounds in relation to their anti-inflammatory and cytotoxic activity are obtained. The analysis of the fluorescence kinetics of the compounds was carried out. The cytotoxic activity of the samples was investigated in the Brine Schrimp test using Artemia salina. All compounds have cytotoxicity, which suggests a lack of selectivity of chemotherapeutic action. In general, the presence of a cytotoxic effect confirms the reality of antimicrobial action. The results of the study of the antibacterial and antifungal activity of the synthesized new fulleropyrrolidines and their starting substrates are described (S. aureus 505, Bacillus subtilis, Str.agalactiae, E. Coli M-17, Ps.aeruginosa, Candida аlbicans, Penicillium citrinum, Aspergillus niger, Aspergillus flavus, Trichophyton mentagraphytos, Epidermophyton fioccosum). As a result of the study of the potential antifungal activity of the compounds, it was found that only two drugs inhibit the growth of test cultures in vitro. All other studied samples have practically no activity against the yeast fungi Candida albicans. In general, the presence of a cytotoxic effect in the studied fullerene compounds confirms the reality of the antimicrobial action.

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Synthesis and structure of N-methyl-1-[(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)phenyl]fullerene-C60-[1,9-c]pyrrolidine

Cited by 5 publications

References 8 publications

Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning

Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning

Synthesis of Properties N-Methyl-2-(Pyrid-4-Yl)-3,4-Fulleropyrrolidine

Indicators of Cell Metabolism in Vitro in Researches of Anti-Inflammatory and Cytotoxic Effects of Fulleropyrrolidines С60 and Their Initial Substrates

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