Synthesis and Anti-cancer Activity of Some Novel 5-Azacytosine Nucleosides

Abstract

1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain α and β anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2′-deoxy-4′-thio-5-azacytidine (3β) was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported.     

Synthesis and Anti-HIV Properties of 1,2,4,6-Thiatriazin-3-one 1,1-Dioxtoe Nucleosides

Abstract

Synthesis of 1,2,4,6-thiatriazine 1,1-dioxide nucleosides is now reported for the first time. In order to know the conformation of the nucleosides, a NMR study has been carried out. Anti-HIV-1 and HIV-2 properties of the nucleosides have been tested. These compounds have not shown activity at subtoxic concentrations.     

Synthesis and Biological Activity of Modified Thiopyrimidine Nucleosides

Abstract

N³ -β-D-glucopyranosyl, galactopyranosyl and xylopyranosyl 6-methyl-2-methylthiouracil and their 5-bromo derivatives have been synthesized by coupling an a-acetobromosugar with the corresponding thiouracil. The new modified thiouridine analogues were evaluated for their inhibitory activity against Human Immunodeficiency Virus (HIV) replication in MT-4 cells as well as for their cytotoxicity.     

Synthesis and Bioactivity of Novel Trisubstituted Triazole Nucleosides

A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity.     

Synthesis and Biological Activity of Chloroethyl Pyrimidine Nucleosides

The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.     

Nucleosides,XLIV1 Synthesis,Properties and Biological Activity of Indazole Nucleosides

Abstract

Various new haloindazole-1-β-D-ribofuranosides (10-17,20,21) and a 2-β-D-ribofuranoside (18) have been synthesized by the fusion method and by direct halogenations, respectively. The new nucleosides have been characterized by UV and ¹H NMR spectra as well as pK_a determinations. Indazole ribofuranosides behave in aqueous acid like purine and benzimidazole nucleosides showing the same mechanism of cleavage of the glycosidic bonds. Toxicity studies against various cell populations indicate only little biological activities.     

Synthesis of Novel Carbocyclic Nucleosides with a Modified Cyclopentane Ring and Evaluation of Their Antiviral Activity

Abstract

New carbocyclic nucleosides with purine (compounds 2a-2c), 8-azapurine (compounds 2d and 2e) or pyrimidine (compound 3) as base were prepared and assayed for in vitro activity.     

Synthesis and Cytotoxic Activity of Novel 5-Substituted-1-(β-L-Arabinofuranosyl) Pyrimidine Nucleosides

A series of new 5-halogeno-1-(ß-L-arabinofuranosyl)uracils and their cytosine analogues were synthesized by halogenation of ara-L-uridine and ara-L-cytidine, respectively. The 5-(2-thienyl) and 5-halogenothienyl derivatives of both series were also prepared in excellent yields by Stille coupling followed by halogenation. All of these syntheses were based on benzoyl-protected derivatives. In vitro cytotoxicity experiments carried out using L1210 mouse leukemia cells showed that 5-(2-thienyl)-ara-L-uridine was the most potent compound of the new compounds; the majority of the analogues were not effective up to 200 μM concentrations.     

Facile Synthesis and Anti-Tumor Cell Activity of Se-Containing Nucleosides

Many organic compounds containing selenium have shown anticancer effects and some have been used in chemoprevention of cancers and other diseases. Though Se-containing amino acids are generally used for these purposes, the natural nucleosides may also be used as Se-carriers for these important applications. Therefore, we describe here the convenient synthesis of the new 3′-MeSe-thymidine nucleoside and the other uridine and thymidine derivatives modified with MeSe at the 2′ and 5′ positions, and report their anti-tumor activity against prostate cancer cell lines. Our work demonstrates for the first time anticancer activity of the methylseleno nucleosides.     

Synthesis and Antiviral Activities of Some Novel Carbocyclic Nucleosides

Abstract

cis-3-Aminomethylcyclopentylmethanol (4), prepared from norbornene (5) in four steps and 51 % overall yield, was used as a precursor in the synthesis of carbocylic nucleosides 13–18 containing guanine and 8-azaguanine bases. None of these compounds had appreciable activity against fourteen viruses in the concentration range tested. Compounds 13 and 16 showed cytotoxicity to all or part of the cell lines used.     

Design,Synthesis and Anti-HIV Activity of Homologous PMEA Derivatives

This article describes an efficient route for synthesizing novel cyclopropyl homologous PMEA analogues. The condensation of the bromide 8 with nucleosidic bases (A, U, T, C, 5-FU, G) under standard nucleophilic substitution and deprotection conditions, afforded the target phosphonic acid analogues 14～18 and 21. These compounds were evaluated for their potential antiviral properties against various viruses. Guanine derivative 21 showed significant antiviral activity.     

Synthesis of Some Novel Acyclolumazine N-1 Nucleosides

Abstract

Reactjon of (2-acetoxyethoxy)methyl bromide with the silylated lumazine bases (1-6) in the presence of n-Bu₄NI leads to the formation of the nucleosides 8, 10, 12, 14, 16 and 18 respectively. Deacetylation with methanolic ammonia afforded the free nucleosides 9, 11, 13, 15, 17 and 19, respectively, in good yields. Structural proofs of the newly synthesized compounds are based on elemental analyses, UV and ¹H-NMR spactra. None of the acyclic nucleosides exhibited antiviral activity against HSV-1 in vitro.     

The Synthesis of Novel 5-Trifluoroethoxy Pyrimidine Nucleosides

Abstract

The syntheses of 5-(2, 2, 2-trifluoroethoxy)uracil, 5-(2, 2, 2-trifluoroethoxy)arabinouridine and 5-(2, 2, 2-trifluoroethoxy) uridine are described.     

New Acyclic Quinoxaline Nucleosides. Synthesis and Anti-Hiv Activity

A series of acyclonucleosides substituted 1-(4,5-dihydroxypentyl) (13-8) and 2-(4,5-dihydroxypentyloxy)quinoxalines (19-24) were synthesized by the sharpless asymmetric dihydroxylation of the derivatives 1-6 and 7-12, respectively. Treatment of the quinoxaline base 26 with (R)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl-p-toluenesulfonate (27) in the presence of NaH/DMF furnished 28. Acid hydrolysis of 28 gave 1-(2,3-dihydroxypropyl)-6,7-dimethyl-quinoxaline-2-one (29). Alternatively, 29 was prepared by sharpless dihydroxylation of 30. All the compounds were evaluated for their in vitro anti-HIV-1 and HIV-2 in MT-4 cell and found inactive, except 29, which showed inhibition of HIV-1 with EC₅₀ value of 0.15 ± 0.1 μg/ml and a therapeutic index (SI) of 73.     

Synthesis and Antimicrobial Evaluation of Novel Pyrazolones and Pyrazolone Nucleosides

The synthesis of a novel series of 4-arylhydrazono-5-methyl-1,2-dihydropyrazol-3-ones 4a–h, and their N ²-alkyl and acyclo, glucopyranosyl, and ribofuranosyl derivatives is described. K₂CO₃ catalyzed alkylation of 4a–h with allyl bromide, propargyl bromide, 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide proceeded selectively at the N ²-position of the pyrazolinone ring. Glycosylation of 4a with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose under Vorbruggen glycosylation conditions gave the corresponding N ²-4-arylhydrazonopyrazolone ribofuranoside 9a in good yield. Conventional deprotection of the acetyl protected nucleosides furnished the corresponding 4-arylhydrazonopyrazolone nucleosides in good yields. Selected numbers of the newly synthesized compounds were screened for antimicrobial activity. Compounds 4b, 12a, and 14d showed moderate activities against Aspergillus flavus, Penicillium sp., and Escherichia coli.     

Acyclic Nucleotides Related to Clitocine: Synthesis and Anti-HIV Activity

Abstract

The syntheses and antiviral activity of analogues of the anti-HIV agents PMEA, PMEDAP, (R)-PMPA, (R)-PMPDAP are described. In these analogues the adenine moiety is replaced by 4,6-diamino-5-nitro-pyrimidine (the aglycon of clitocine) or 2,4,6-triamino-5-nitro-pyrimidine. The synthesis of similar acyclic phosphonates related to PMEG and (R)-2′-methyl-PMEG is also reported. Some compounds proved to be active as anti-HIV agents.     

Synthesis and Anti-HIV Activity of a New Hexopyranoside Analogue of AZT

Abstract

The glycosylation of thymine (13) with 12 in the presence of trimethylsilyl triflate promoter afforded the α, β-L-ribo-hexopyranosy1-nucleoside analogue 14a,b. After removal of the protecting group 1-(3-azido-2,3,6-trideoxy-α and β-L-ribo-hexopyranosyl) -thymine (15a and 15b) were isolated in anomerically pure form in a ratio of 1:20. The anti-HIV activity of the major product 15b was examined, in comparison with AZT, on H9 lymphoid cell-line.     

Synthesis and Biological Activity of 5-Fluoro-2-thiocytosine Nucleosides

Abstract

Two pathways are described for the synthesis of the 2′-deoxynucleosides of 2-thiocytosine and 5-fluoro-2-thiocytosine: (a) by nucleoside condensation, (b) by amination of the corresponding nucleosides of 2,4-dithiouracil. Biological activities vs two cell systems are described. The nucleosides are moderate to weak substrates of deoxycytidine kinase and, partly as a result of this, reasonable good inhibitors of the enzyme     

Terminal Fluoroolefins. The Synthesis of Novel Carboacyclic Nucleosides

Abstract

A facile preparation of ketone 7 from butanetriol acetonide 5 is reported, and its utility for the synthesis of novel carboacyclic nucleosides 3E, 3Z, 4E and 4Z by the selective manipulation of multiple functionalities is demonstrated.     

Synthesis and Biological Activity of 2-Aminopurine Methylenecyclopropane Analogues of Nucleosides

Abstract

Synthesis and biological activity of 7- and 9-isomers (Z+E) of methylenecyclopropane analogues of 2-aminopurine nucleosides is described. The (S,Z)-9-isomer is a substrate for xanthine oxidase.