Studies on the synthesis and biological activities of 4′-(R)-hydroxy-5′-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines

Yu, Hongwu; Zhang, Liangren; Zhou, Jinchuan; Ma, Ling-Tai; Zhang, Lihe

doi:10.1016/0968-0896(96)00048-x

Cited by 38 publications

(17 citation statements)

References 19 publications

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“…According to our previous studies, 17 , 19 the force-field parameters for D-/L-IsoT and 2′-dI were obtained by quantum chemical methods using the Gaussian 09 program (Gaussian 09, Gaussian, Inc.). At the B3LYP/6-31G* level of theory, we optimized the entire geometry and calculated the HF/6-31G* electrostatic potential.…”

Section: Methodsmentioning

confidence: 99%

“…Isonucleosides (IsoNA) ( Figure 1 ) are a novel type of nucleoside analog in which the nucleobase is linked to another position of the ribose other than C-1′, to be precise, C-2′ in our research. 17 Previous work has shown that D-/L-isoNA incorporated at the proper sites in oligos can increase the activity of antisense nucleotides, DNAzyme, small interfering RNAs (siRNAs), and aptamers. 18 , 19 , 20 , 21 , 22 , 23 , 24 Furthermore, as a naturally occurring base, 2′-deoxyinosine (2′-dI) ( Figure 1 ) offers a huge advantage in non-immunogenic clinical application.…”

Section: Introductionmentioning

confidence: 99%

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The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

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In this study, chemical modification of 2′-deoxyinosine (2′-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement. They stabilized the G-quadruplex, remained highly resistant to serum degradation and specificity for nucleolin, further inhibited tumor cell growth, exhibited a stronger ability to influence the different phases of the tumor cell cycle, induced S-phase arrest, promoted the inhibition of DNA replication, and suppressed the unwound function of a large T antigen as powerful as AS1411. The microarray analysis and TaqMan PCR results showed that FCL-II can upregulate the expression of four breast-cancer-related, lowly expressed miRNAs and downregulate the expression of three breast-cancer-related, highly expressed miRNAs (>2.5-fold). FCL-II resulted in enhanced treatment effects greater than AS1411 in animal experiments (p < 0.01). The computational results further proved that FCL-II exhibits more structural advantages than AS1411 for binding to the target protein nucleolin, indicating its great potential in antitumor therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

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“…The lack of an N -glycosidic bond in isonucleosides linking the sugar and nucleobase moieties confers them a higher chemical and enzymatic stability than that of nucleosides. Most of the reported isonucleosides possess the nucleobase linked to furanose systems at C-2 or at C-3 [3,4,5,6,7,8,9,10,11], among which some molecules exhibited anticancer [4,5] or antiviral [6,7,8,9,11] activities. Pyranosyl isonucleosides have been relatively less exploited and the few reported examples include 2′-fluoroarabino-2′-yl pyrimidine derivatives [12], which displayed anticancer activities, and pyranos-6′-yl isonucleosides [13,14], which resulted from our previous investigations and showed selective and moderate to good inhibition of acetylcholinesterase (AChE).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

et al. 2019

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Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5′ and 6′-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer’s disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5′-isonucleosides and xylofuranos-5′-yl or glucos-6′-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing N-isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, Ki = 3.1 µM) and butyrylcholinesterase (BChE, Ki = 5.4 µM), and a 2-O,4-O-bis-xylofuranos-5′-yl uracil derivative, which displayed moderate inhibition of AChE (Ki = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts.

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“…Literature reports have shown that naturally occurring purine as well as their synthetic counterparts exhibit a wide range of biological activity . Di, tri and tetra substituted purines have been accounted for possessing antiviral and antitubercular properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 6‐[4‐(4‐Propoxyphenyl)piperazin‐1‐yl]‐9H‐purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study

Nadaf

Najare

Garbhagudi

et al. 2020

Chemistry & Biodiversity

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A series of novel alkyl substituted purines were synthesized. 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for Nalkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like 1 H-NMR, 13 C-NMR, FT-IR and EI-MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski's parameters and have exhibited good drug-like properties.

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Studies on the synthesis and biological activities of 4′-(R)-hydroxy-5′-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines

Cited by 38 publications

References 19 publications

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Synthesis and Biological Evaluation of Structurally Varied 5′-/6′-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

Synthesis of 6‐[4‐(4‐Propoxyphenyl)piperazin‐1‐yl]‐9H‐purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study

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