Table 3.
Summary of synthetic adenosine derivatives, methods and physiological action of the last 25 years.
| Adenosine Derivatives by Substitution Reactions | |||
|---|---|---|---|
| Adenosine Derivatives Series | Methods of Synthesis and Biological Essay | Target Interaction | Refs. |
| C8-amino-N6-disubstitution adenosine |
Precursors: • N6-derivative-8-halide adenosine. • 8-aminoalkyl derivative 6-chloropurine riboside • 6,8-dichloropurine riboside. Reaction type: Double selective substitution. Essay: rat cerebral cortex cells and striated |
A1 and A2A receptors | [48] |
| • 2-alkyladenosine • 2-alkynyl-N6-alkyladenosine. • Adenosine-5'-N6-ethyluronamide |
Precursors: • 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-iodopurine. • 2-iodoadenosine • 2-iodine-N6-alkyladenosine Reaction type: Double and triple selective substitution. Essay: Rat ovary cells transfected with human recombinant DNA (adenosine receptors) and platelet. |
A2 and A3 receptors | [3, 45, 46] |
| 2-Substitution-N6-methyl adenosine. |
Precursor: • 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-iodopurine. Reaction type: Double and triple selective substitution. |
A3 receptor | [49] |
| • 2-alkyloxy ether • 2-alkylaryl • 2-amino ether • 2-thioether |
Precursor: • 2-adenosine chlorine. Reaction type: Nucleophilic substitution. Essay: Rat ovary cells (CHO) |
A3 receptor | [50, 51] |
| • N6-alkyladenosine derivatives |
Precursor: • 6-chloropurine riboside. Reaction type: Nucleophilic substitution. Essay: Cell lines of bladder carcinoma T24 and J88 types. |
Carcinoma cell lines | [52] |
| • N6-biotinyl-8-azidoadenosine probe |
Precursor: • Inosine Reaction type: Nucleophilic substitution. Essay: Cell lines of bladder carcinoma T24 and J88 types. |
Adenosine Deaminasa (cADA) | [57] |
| • 2’-deoxymethylene nucleosides |
Precursor: • Guanosine Reaction type: Nucleophilic substitution;, oxidation by Swern method; methylenation by Wittig reaction and nonaqueous diazotization (substitution reaction) Essay: Mouse lymphocytic leukemia cell line (L1210) |
Ribonucleotide Reductase Enzyme (RNR) | [58] |
| • N-benzylated-7-deazaadenosine analogues |
Precursor: • Turbercidin Reaction type: Alkylation and SNAr Essay: Murine leukemia (L1210) cellsand human T-lymphocyte (CEM),cervix carcinoma (HeLa), prostateadenocarcinoma (PC-3), andkidney carcinoma (Caki-1) cells, and Nucleoside Transport. |
hENT1 and pool cell lines | [74] |
| Adenosine Derivatives by Complexation Reactions | |||
| [Ru2(CH3CO2)4(C10H13N5O4)2] Cl |
Precursor: • Adenosine. Reaction type: Complexation reaction Essay:Growing Escherichia coli. |
E. coli bacteria | [61] |
| Adenosine Derivatives by Complexation Reactions | |||
| Adenosine Derivatives Series | Methods of Synthesis and Biological Essay | Target Interaction | Refs. |
| • Trans-[PtCl2(N6-(substituted-benzyl) adenosine)2]•*Solv. • Trans-[PtCl2(2-chloro-N6-(substituted-benzyl) adenosine)2]•*Solv. |
Precursor: • K2[PtCl4] • 6-chloropurine-9-ribose • 2,6-dichloropurine-9-ribose. • Amine derivatives. Reaction type: Complexation reaction. Essay: Osteosarcoma (HOS) and breast adenocarcinoma. |
Carcinoma cell lines | [62, 63] |
| Adenosine Derivatives by Conjugation and Coupling Reactions | |||
| • N6-amino derivatives of adenosine 5'- monophosphate. • 5'-adenosine phosphoramidate amino derivatives • 5'-N6-fluorescein derivatives AMP • 5'- and N6 - biotin derivatives AMP |
Precursor: • Diamines • AMP • 6-chloropurine riboside-5-monophosphate. • 5(6)-carboxifluorescein-N- hydroxysuccinimide ester (FAM-SE). • Biotin N-hydroxysuccinimide ester (biotin-SE) Reaction type: Coupling and direct displacement. Essay: In vitro RNA transcription, Electrophoresis. |
RNA | [65] |
| • Folate-adenosine-5'-(13-amino-4,7, 10-trioxa tridecyl) phosphoramidate) • Folate-adenosine-5'-(6-aminohexyl) phosphoramidate |
Precursor: • AMP, N-methylimidazole and hidrochloruro N-(3-dimethylaminopropyl)-N'-Ethylcarbodiimide (EDC). • Diamine • Folic acid. • NHS Reaction type: Conjugation. Essay: RNA sequence in vitro |
RNA | |
| • Homologated apio analogues of IB-MECA and Cl-IB-MECA |
Precursor: • IB-MECA and Cl-IB-MECA • Glycosyl donor • 2,6-dichloropurine • 3-Halobenzyl amines Reactions types: • Controlled oxidative cleavage of vicinal diol. • Mitsunobu condensation reactions. Essay: Docking molecular and MM-GBSA. |
A3 receptor | [69] |
| • 2,6-diamino-8-azapurine sulfate |
Precursor: • Ribose-1-phosphate • D-aaPur • α-D-ribose-1-phosphate • 8-azaguanine Reactions types: Ribosylation Essay: Escherichia coli culture and solution purine-nucleoside phosphorylase. |
Purine-nucleoside phosphorylase (PNP) and bacteria E.coli | [87] |
| • N6-(2-methoxybenzyl)adenosine (2 OMeL) • N6-(4-methoxybenzyl)adenosine (4 OMeL) • N6-(4-methylbenzyl)adenosine (4MeL) • N6-(2-chlorobenzyl)adenosine (2 ClL) • N6-(4-fluorobenzyl)adenosine (4 FL) |
Precursor: • N6-benzyladenosine derivative • K2[Pt(ox)2]·2H2O Reactions types: • One-step synthetic procedure using the reaction of potassium bis(oxalato)platinate(II) Essay: Cancer cells (osteosarcoma and breast adenocarcinoma) |
Human cancer cell lines | [63] |
| Adenosine Derivatives by Conjugation and Coupling Reactions | |||
| Adenosine Derivatives Series | Methods of Synthesis and Biological Essay | Target Interaction | Refs. |
| • 5’-(N-aminoacyl)-sulfonamido-5’-deoxyadenosine |
Precursor: • adenosine Reactions types: Mitsunobu condensation reactions or coupling and conjugation. Essay: • E. coli, S. Lutea and C. Albicans. • In vitro aminoacylation experiments. |
Bacteria, fungi and Aminoacyl tRNA synthetases (aaRS) in vitro |
[67] |
| • Sulfamide adenosine derivatives (pGlu-SA) |
Precursor: • Adenosine. • 5'-amino-5'-deoxyadenosine • L-pyroglutamic acid Reactions types: Conjugation and coupling. Essay:Cancer cells |
Aminoacyl tRNA synthetases (aaRS) |
[70] |
| • 8-brominated adenosine derivatives • 8-aminated adenosine derivatives |
Precursor: • Isopropylidene-protected-adenosine Reactions types: Oxidation and amide-coupling Essay: Inhibitory activity against E. coli and P. Falciporum IspE. |
IspE enzyme | [72] |
| • Truncated N6-substituted 4’-oxoadenosine • Truncated N6-substituted 4’-thioadenosine |
Precursor: • 2,3-O-isopropylidene-D-erythronic-γ-lactone. Reactions types: lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions. Essay: • Chinese hamster ovary (CHO) cells (A1 or A3R) • Human embryonic kidney (HEK-293) cells (A2AAR). |
A3 and A2A receptors | [73] |
| • 7-deaza-cyclic adenosine-5’-diphosphate carbocyclic ribose. • 7-deaza-7-bromo-cyclic adenosine-5’-diphosphate carbocyclic ribose. |
Precursor: • 2,3-disubstituted pyrrole nucleoside • Carbocyclic ribosyl amine • Imidazole nucleoside Reactions types: Ag+ promoted intramolecular condesation and coupling reaction. Essay: Hemicentrotus pulcherrimus sea urchin egg homogenate. |
Sea urchin egg homogenate system | [77] |
| • (N)-Methanocarba-5′-ester adenosine derivatives |
Precursor: • (N)-methanocarba adenosine Reactions types: oxidation, substitution nucleophilic aromatic and coupling. Essay: Dopamine transporter (DAT) |
A3R and DAT | [79] |
(*) Solvent = H2O or MeOH.
(Source: Prepared by the author).