Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A1 adenosine receptor agonists

Berzina, Мaria Ya.; Eletskaya, Barbara Z.; Kayushin, Alexei L.; Dorofeeva, Elena V; Lutonina, Olga I.; Fateev, Ilja V.; Paramonov, Alexander S.; Костромина, М. А.; Zayats, Evgeniy A.; Abramchik, Yu. A.; Maltsev, D. V.; Науменко, Л. В.; Таран, А. С.; Yakovlev, D. S.; Спасов, А. А.; Мирошников, А. И.; Есипов, Р. С.; Konstantinova, Irina D.

doi:10.1016/j.bioorg.2022.105878

Cited by 3 publications

(9 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently published an article describing the synthesis of purine ribosides 1a – 12a ( Scheme 1 ) modified with chiral amino acid amides at the C6 position of the purine [ 35 ]. We showed that derivatives with tyrosine, valine, and serine residues exhibit the properties of A 1 adenosine receptor partial agonists.…”

Section: Resultsmentioning

confidence: 99%

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

Eletskaya

Berzina

Fateev

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC50 = 16 μM) close to that of Nelarabine (IC50 = 3 μM) and was evaluated as active.

show abstract

Section: Resultsmentioning

confidence: 99%

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

Eletskaya

Berzina

Fateev

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The NMR spectra analysis of acylated nucleosides 1a-12a and ribosides 1b-12b [5] revealed the presence of a significant amount of the nucleoside second form. The content of the mini-form component for nucleosides 1a,b-12a,b varied from 11 to 32% of the main form (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

“…Interest in the synthesis of new substituted adenosines remains high. Among these nucleosides, effective antimetabolites [1,2] and adenosine receptor agonists [3][4][5] have been found. NMR spectroscopy is a powerful tool for studying the adenosine derivatives.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy

Berzina,

Eletskaya,

Kayushin

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Two forms were found in the NMR spectra of N6-substituted 2-chloroadenosines. The proportion of the mini-form was 11–32% of the main form. It was characterized by a separate set of signals in COSY, 15N-HMBC and other NMR spectra. We assumed that the mini-form arises due to the formation of an intramolecular hydrogen bond between the N7 atom of purine and the N6–CH proton of the substituent. The 1H,15N-HMBC spectrum confirmed the presence of a hydrogen bond in the mini-form of the nucleoside and its absence in the main form. Compounds incapable of forming such a hydrogen bond were synthesized. In these compounds, either the N7 atom of the purine or the N6–CH proton of the substituent was absent. The mini-form was not found in the NMR spectra of these nucleosides, confirming the importance of the intramolecular hydrogen bond in its formation.

show abstract

“…Alteration of AR expression and function has been shown in many diseases, making these receptors a potential target for therapy: A1AR -in CVD (ischemia/reperfusion, myocardial infarction, angina pectoris, hypertension, cardiomyopathy, arrhythmia, chronic heart failure [15][16][17][18][19][20][21][22], obesity [23], cancer [24], increased intraocular pressure (glaucoma) [25]); A2AAR -in CVD [26], obesity [23], Parkinson's disease (PD) [27], and cancer [24]; A2BAR -in inflammation [28], chronic obstructive pulmonary disease [29], and diabetes [30]; A3AR -in inflammation [31], glaucoma [32], rheumatoid arthritis [33], and stroke [34].…”

Section: Introductionmentioning

confidence: 99%

Problems and prospects for finding new pharmacological agents among adenosine receptor agonists, antagonists, or their allosteric modulators for the treatment of cardiovascular diseases

Perfilova,

Muzyko,

Taran

et al. 2023

BIOMED KHIM

View full text Add to dashboard Cite

A1-adenosine receptors (A1AR) are widely distributed in the human body and mediate many different effects. They are abundantly present in the cardiovascular system, where they control angiogenesis, vascular tone, heart rate, and conduction. This makes the cardiovascular system A1AR an attractive target for the treatment of cardiovascular diseases (CVD). The review summarizes the literature data on the structure and functioning of A1AR, and analyzes their involvement in the formation of myocardial hypertrophy, ischemia-reperfusion damage, various types of heart rhythm disorders, chronic heart failure, and arterial hypertension. Special attention is paid to the role of some allosteric regulators of A1AR as potential agents for the CVD treatment.

show abstract

Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A1 adenosine receptor agonists

Cited by 3 publications

References 63 publications

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy

Problems and prospects for finding new pharmacological agents among adenosine receptor agonists, antagonists, or their allosteric modulators for the treatment of cardiovascular diseases

Contact Info

Product

Resources

About