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23 pages, 1871 KB

Open AccessArticle

Efficient Synthesis of α-Branched Purine-Based Acyclic Nucleosides: Scopes and Limitations of the Method

by Jan Frydrych, Lenka Poštová Slavětínská, Martin Dračínský and Zlatko Janeba

Molecules 2020, 25(18), 4307; https://doi.org/10.3390/molecules25184307 - 19 Sep 2020

Cited by 8 | Viewed by 5725

An efficient route to acylated acyclic nucleosides containing a branched hemiaminal ether moiety is reported via three-component alkylation of N-heterocycle (purine nucleobase) with acetal (cyclic or acyclic, variously branched) and anhydride (preferentially acetic anhydride). The procedure employs cheap and easily available acetals, [...] Read more.

An efficient route to acylated acyclic nucleosides containing a branched hemiaminal ether moiety is reported via three-component alkylation of N-heterocycle (purine nucleobase) with acetal (cyclic or acyclic, variously branched) and anhydride (preferentially acetic anhydride). The procedure employs cheap and easily available acetals, acetic anhydride, and trimethylsilyl trifluoromethanesulfonate (TMSOTf). The multi-component reaction is carried out in acetonitrile at room temperature for 15 min and provides moderate to high yields (up to 88%) of diverse acyclonucleosides branched at the aliphatic side chain. The procedure exhibits a broad substrate scope of N-heterocycles and acetals, and, in the case of purine derivatives, also excellent regioselectivity, giving almost exclusively N-9 isomers. Full article

(This article belongs to the Special Issue Advances in Nucleoside/Nucleotides and Nucleic Acid Chemistry: A Theme Issue in Honor of Prof. Dr. Piet Herdewijn)

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17 pages, 2827 KB

Open AccessArticle

Synthesis, Structural Characterization, and Biological Activity of New Pyrazolo[4,3-e][1,2,4]triazine Acyclonucleosides

by Mariusz Mojzych, Zofia Bernat, Zbigniew Karczmarzyk, Joanna Matysiak and Andrzej Fruziński

Molecules 2020, 25(1), 221; https://doi.org/10.3390/molecules25010221 - 5 Jan 2020

Cited by 9 | Viewed by 5180

Abstract

A series of new pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides 2–5 and 8 were prepared and evaluated for their anticancer activity against human cancer cell lines (MCF-7, K-562) and CDK2/E, as well as Abl protein kinases inhibitors. Lipophilicity of the compounds was determined [...] Read more.

A series of new pyrazolo[4,3-e][1,2,4]triazine acyclonucleosides 2–5 and 8 were prepared and evaluated for their anticancer activity against human cancer cell lines (MCF-7, K-562) and CDK2/E, as well as Abl protein kinases inhibitors. Lipophilicity of the compounds was determined using C-18 and immobilized artificial membrane (IAM) chromatography. In order to confirm the molecular structures and synthesis pathway of new acyclonucleosides, X-ray analysis was performed for model compound 3. Theoretical calculations at the DFT/B3LYP/6-311++G(d,p) level were used for the characterization of electronic structures of 1–8. The potential antiviral activity of acyclonucleosides 2–8 was tested in silico using molecular docking method. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 1106 KB

Open AccessArticle

Carboxylated Acyclonucleosides: Synthesis and RNase A Inhibition

by Kaustav Chakraborty, Swagata Dasgupta and Tanmaya Pathak

Molecules 2015, 20(4), 5924-5941; https://doi.org/10.3390/molecules20045924 - 3 Apr 2015

Cited by 1 | Viewed by 7755

Abstract

Strategically designed carboxylated acyclonucleosides have been probed as a new class of RNase A inhibitors. Several experimental and theoretical studies have been performed to compile relevant qualitative and quantitative information regarding the nature and extent of inhibition. The inhibition constant (K_i [...] Read more.

Strategically designed carboxylated acyclonucleosides have been probed as a new class of RNase A inhibitors. Several experimental and theoretical studies have been performed to compile relevant qualitative and quantitative information regarding the nature and extent of inhibition. The inhibition constant (K_i) values were determined using a UV-based kinetics experiment. The changes in the secondary structure of the enzyme upon binding with the inhibitors were obtained from circular dichroism studies. The binding constants for enzyme-inhibitor interactions were determined with the help of fluorescence spectroscopy. Docking studies were performed to reveal the possible binding sites of the inhibitors within the enzyme. The cytosine analogues were found to possess better inhibitory properties in comparison to the corresponding uracil derivatives. An increment in the number of carboxylic acid groups (-COOH) in the inhibitor backbone was found to result in better inhibition. Full article

(This article belongs to the Special Issue Nucleoside Modifications)

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13 pages, 1086 KB

Open AccessArticle

From Formamide to RNA, the Path Is Tenuous but Continuous

by Samanta Pino, Judit E. Sponer, Giovanna Costanzo, Raffaele Saladino and Ernesto Di Mauro

Life 2015, 5(1), 372-384; https://doi.org/10.3390/life5010372 - 30 Jan 2015

Cited by 37 | Viewed by 11858

Abstract

Reactions of formamide (NH₂COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest. Formamide chemistry potentially satisfies all of the steps from the [...] Read more.

Reactions of formamide (NH₂COH) in the presence of catalysts of both terrestrial and meteoritic origin yield, in plausible and variegated conditions, a large panel of precursors of (pre)genetic and (pre)metabolic interest. Formamide chemistry potentially satisfies all of the steps from the very initial precursors to RNA. Water chemistry enters the scene in RNA non-enzymatic synthesis and recombination. Full article

(This article belongs to the Special Issue The Origins and Early Evolution of RNA)

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16 pages, 565 KB

Open AccessArticle

Synthesis of New 1,2,3-Triazol-4-yl-quinazoline Nucleoside and Acyclonucleoside Analogues

by Abdelaaziz Ouahrouch, Moha Taourirte, Joachim W. Engels, Soumaya Benjelloun and Hassan B. Lazrek

Molecules 2014, 19(3), 3638-3653; https://doi.org/10.3390/molecules19033638 - 24 Mar 2014

Cited by 30 | Viewed by 9717

Abstract

In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV [...] Read more.

In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro. Full article

(This article belongs to the Section Medicinal Chemistry)

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21 pages, 713 KB

Open AccessArticle

C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

by Andrijana Meščić, Svjetlana Krištafor, Ivana Novaković, Amar Osmanović, Ursina Müller, Davorka Završnik, Simon M. Ametamey, Leonardo Scapozza and Silvana Raić-Malić

Molecules 2013, 18(5), 5104-5124; https://doi.org/10.3390/molecules18055104 - 2 May 2013

Cited by 8 | Viewed by 7001

Abstract

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields [...] Read more.

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 187 KB

Open AccessArticle

Synthesis of 1,4-Disubstituted Mono and Bis-triazolocarbo-acyclonucleoside Analogues of 9-(4-Hydroxybutyl)guanine by Cu(I)-Catalyzed Click Azide-Alkyne Cycloaddition

by Jamal Krim, Moha Taourirte and Joachim W. Engels

Molecules 2012, 17(1), 179-190; https://doi.org/10.3390/molecules17010179 - 27 Dec 2011

Cited by 25 | Viewed by 6958

Abstract

A series of novel mono-1,2,3-triazole and bis-1,2,3-triazole acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine was prepared via copper(I)-catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurine, N-1-propargylpyrimidines/as-triazine with the azido-pseudo-sugar 4-azidobutylacetate under solvent-free microwave conditions, followed by treatment with K₂CO₃/MeOH, or NH₃ [...] Read more.

A series of novel mono-1,2,3-triazole and bis-1,2,3-triazole acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine was prepared via copper(I)-catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurine, N-1-propargylpyrimidines/as-triazine with the azido-pseudo-sugar 4-azidobutylacetate under solvent-free microwave conditions, followed by treatment with K₂CO₃/MeOH, or NH₃/MeOH. All compounds studied in this work were screened for their antiviral activities [against human rhinovirus (HRV) and hepatitis C virus (HCV)] and antibacterial activities against a series of Gram positive and negative bacteria. Full article

(This article belongs to the Section Medicinal Chemistry)

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2 pages, 115 KB

Open AccessShort Note

3-Bromomethyl-1,5-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazine and 3-Dibromomethyl-1,5-diphenyl-1H-pyrazolo[4,3-e][1,2,4]triazine

by Mariusz Mojzych

Molbank 2005, 2005(4), M432; https://doi.org/10.3390/M432 - 1 Oct 2005

Viewed by 2904

Abstract

As part of our research programme we have synthesized the title compounds as valuable intermediates for the preparation of acyclonucleosides-biologically active molecules.[...] Full article

7 pages, 41 KB

Open AccessArticle

Synthesis of New Bis-Alkylated Phosphono Alkenyl Acyclonucleosides : (Z) and (E)-Diethyl-2-(3-alkyl pyrimidin-1-yl)ethylen-1-yl Phosphonate

by A. Rochdi, M. Taourirte, H. B. Lazrek, J. L. Barascut and J. L. Imbach

Molecules 2000, 5(10), 1139-1145; https://doi.org/10.3390/51001139 - 31 Oct 2000

Cited by 8 | Viewed by 8009

Abstract

The E- and Z- phosphonoalkenyl acyclonucleosides of uracil and thymine were synthesized under Michael addition conditions. Introduction of an alkyl, alkenyl or alkynyl group at the N-3 position of the pyrimidine moiety was accomplished using potassium carbonate in DMF. Full article

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