Catalytic cyclometallation in steroid chemistry III1Steroids 78 (12–13) (2013) 1298–1303 (http://dx.doi.org/10.1016/j.steroids.2013.09.007).1: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity

D’yakonov, Vladimir A.; Dzhemileva, Lilya U.; Tuktarova, Regina A.; Макаров, А. А.; Islamov, Ilgiz I.; Mulyukova, Alfiya R.; Джемилев, У. М.

doi:10.1016/j.steroids.2015.08.006

Cited by 28 publications

(12 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interest in such 5Z,9Z‐diene fatty acids arises from their antimalarial, antimicrobial, antiviral and antitumor activity . It was subsequently illustrated, that introduction of a lipophilic fragment in the form of steroid framework into the molecule of dienoic acid results in an increase of antitumor activity against HeLa, Hek293, U937, Jurkat, K562 cells, by impacting effectively, among others, the cell cycle via inhibition of topoisomerases I and II.…”

Section: Methodsmentioning

confidence: 99%

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

et al. 2019

Self Cite

View full text Add to dashboard Cite

The present research addresses synthesis of methanofullerenes containing 5Z,9Z-dienoic acid molecules applying the Bingel and Bingel-Hirsch reactions. The cytotoxic activity of the synthesized methanofullerenes against Jurkat, K562, U937, HL60 tumour cells was under study. Hybrid methanofullerenes containing dienoic acids were found to exhibit high in vitro cytotoxicity against these tumour cell lines, produce phasespecific cytotoxic effect during the S and G2 phases of the cell cycle, and are also effective inducers of apoptosis.Building effective systems for targeted drug delivery in the development of anticancer drugs is one of the major challenges of modern pharmacology. This is due to the fact that most antitumor drugs are highly toxic and lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts.No coincidence is the fact that the range of nanoscale delivery vectors of anticancer drugs has expanded significantly since the discovery of fullerenes in 1985. The size, shape and high lipophilicity of C 60 fullerene enable it to penetrate rather easily through cell membranes and are an ideal combination of properties for use as a vector for targeted drug delivery.To date, the transport properties of C 60 fullerene have been successfully demonstrated on a wide range of different pharmaceutical products and anticancer drugs. A perfect example of the use of C 60 fullerene as a means of anticancer drug delivery with the aim of increasing their selectivity is the production of complexes and hybrids with doxorubicin. [1][2][3][4][5][6][7][8] Individual doxorubicin is characterized by low selectivity and cardiotoxicity, its fullerene complex increases both the rate of penetration into cancer cells by 20-30% and the effectiveness increases by 1.5-2 times. [1] The conjugate of doxorubicin with C 60 reduces the tumor volume by 40-60% in vivo compared to an individual doxorubicin, thus increasing life expectancy of mice by 2.5 times. [1,2] Furthermore, enhanced efficiency of the conjugate does not increase the side effects of the initial preparation. [4,5] Chemical binding of C 60 fullerene and its derivatives with doxorubicin does not produce obvious therapeutic effect of this kind, [6,7] but there is still a significant decline in the toxicity of the initial anticancer drug. [7] The main difference between the hybrid and the original doxorubicin molecules is that the hybrid, after penetrating the cell, primarily accumulates in the cytoplasm, and not in the nucleus. [8] Along with doxorubicin, C 60 fullerene complexes and hybrids were also prepared with paclitaxel, [9,10] docetaxel, [11 ] and cisplatin. [12,13] Increased effectiveness of the corresponding drugs was reached with achieved both in vivo and in vitro experiments. Meanwhile, when comparing the therapeutic effect, a considerable decline in the toxicity of these drugs was registered as well.Recently, our research group developed an efficient onepot method for the synthesis of 5Z,9Z-dienoic acids with a yield of ∼ 70% an...

show abstract

Section: Methodsmentioning

confidence: 99%

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…(5Z,9Z)-Tetradeca-5,9-diene-1,14-diol 4 and (5Z,9Z)-tetradeca-5,9-dienedioic acid 5 were synthesized employing the previously developed homo-cyclomagnesiation reaction between tetrahydropyran ether of 5,6-hepta-5,6-dien-1-ol 1 and EtMgBr in the presence of Cp 2 TiCl 2 (5 mol%) as the catalyst [23][24][25][26][27]. Subsequent deprotection of 1,14-bistetrahydropyranyl-5Z,9Z-diene-1,14-diol 3 formed after hydrolysis of magnesacyclopentane 2 in the presence of catalytic amounts of p-toluenesulfonic acid or its oxidation with Jones reagent led to compounds 4 and 5, respectively (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

“…The free terminal amino group in amides 19a-d and 20a-d was protected with the tert-butoxycarbonyl (BOC) group [29]. After removing the BOC protection from compounds 19a-d and 20a-d with trifluoroacetic acid in the chloroform, amides 21a-d and 22a-d were esterified with (5Z,9Z)-tetradeca-5,9-dienedioic acid 5 according to the described method [23] (Scheme 5). The synthesis of LA-fatty acid conjugates linked via diaminoalkane units of different lengths was carried out in several stages.…”

Section: Chemistrymentioning

confidence: 99%

“…Pharmaceuticals 2021, 14, 84 2 of 29Our recent studies in the search for new compounds aimed at treating oncological diseases have shown that the synthesized hybrid molecules based on steroids and cisunsaturated acids are apoptosis inducers in Jurkat, K562, U937, HeLa tumor cell lines, as well as in a specific cell line originally derived from human embryonic kidney cells (HEK293), and can also inhibit in vitro the supercoiled DNA relaxation induced by topoisomerase I [23][24][25][26]. In the development of these studies, we prepared conjugates of LA and (5Z,9Z)-tetradeca-5,9-dienedioic acid, which are linked to each other through ethylene glycol and diaminoalkane spacers of different lengths.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units

et al. 2021

Self Cite

View full text Add to dashboard Cite

For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2–4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.

show abstract

“…It is well known that half of the currently existing medicinal drugs have been, and continue to be, developed on the basis of natural compounds’ skeletons and their numerous synthetic analogues. As the natural compound for the present work, we chose cholesterol, which performs very important functions in the human body [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Cholesterol is a structural component of cell membranes and provides their stability, participates in the biosynthesis of steroid sex hormones and corticosteroids, serves as a basis for the formation of bile acids and vitamin D, and also protects red blood cells from the action of hemolytic poisons.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

2021

Self Cite

View full text Add to dashboard Cite

Catalytic [6π + 2π]-cycloaddition of N-carbocholesteroxyazepine with functionally substituted terminal alkynes and 1,4-butynediol was performed for the first time under the action of the Co(acac)2(dppe)/Zn/ZnI2 three-component catalytic system. The reaction gave previously undescribed but promising 9-azabicyclo[4.2.1]nona-2,4,7-trienes (in 79–95% yields), covalently bound to a natural metabolite, cholesterol. The structure of the synthesized azabicycles was confirmed by analysis of one- and two-dimensional (1H, 13C, DEPT 13C, COSY, NOESY, HSQC, HMBC) NMR spectra.

show abstract

Catalytic cyclometallation in steroid chemistry III1Steroids 78 (12–13) (2013) 1298–1303 (http://dx.doi.org/10.1016/j.steroids.2013.09.007).1: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity

Cited by 28 publications

References 17 publications

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

Contact Info

Product

Resources

About

Catalytic cyclometallation in steroid chemistry III1Steroids 78 (12–13) (2013) 1298–1303 (http://dx.doi.org/10.1016/j.steroids.2013.09.007).1: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity

Cited by 28 publications

References 17 publications

Hybrid Molecules Based on C60 Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

Hybrid Molecules Based on C60 Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

Contact Info

Product

Resources

About

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity

Hybrid Molecules Based on C₆₀ Fullerene and 5Z,9Z‐Dienoic Acids: Synthesis and Cytotoxic Activity