Synthesis, conformational analysis, and biological activity of C-thioribonucleosides related to tiazofurin.

  title={Synthesis, conformational analysis, and biological activity of C-thioribonucleosides related to tiazofurin.},
  author={Palmarisa Franchetti and Stefano Marchetti and Loredana Cappellacci and Hiremagalur N. Jayaram and Joel A. Yalowitz and Barry M. Goldstein and J. L. Barascut and David Dukhan and J. L. Imbach and Mario Grifantini},
  journal={Journal of medicinal chemistry},
  volume={43 7},
The syntheses of furanthiofurin [5beta-D-(4'-thioribofuranosyl)furan-3-carboxamide, 1] and thiophenthiofurin [5beta-D-(4'-thioribofuranosyl)thiophene-3-carboxamide, 2], two C-thioribonucleoside analogues of tiazofurin, are described. Direct trifluoroacetic acid-catalyzed C-glycosylation of ethyl furan-3-carboxylate with 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-D-ribofuranose gave 2- and 5-glycosylated regioisomers, as a mixture of alpha and beta anomers. Ethyl 5-(2,3,5-tri-O-benzyl)-beta-D-(4… Expand
An access to the β-anomer of 4'-thio-C-ribonucleosides: hydroboration of 1-C-aryl- or 1-C-heteroaryl-4-thiofuranoid glycals and its regiochemical outcome.
Results demonstrate that this synthetic method has a wider scope in terms of heterocyclic base structure and unexpected Markovnikov-oriented hydroboration has been observed to lead to the respective 1'-α-boranes. Expand
Additive Pummerer reaction of 3,5-O-(di-tert-butyl)silylene-4-thiofuranoid glycal: a high-yield and beta-selective entry to 4'-thioribonucleosides.
The 4-thio-beta-D-ribofuranosyl derivatives of uracil, thymine, N (4) -acetylcytosine, 6-chloropurine, and 2-amino-6-chlorOPurine were synthesized and can be extended to the beta-selective synthesis of 4'-thIO-C-ribonucleosides. Expand
2-(3-Amino-3-deoxy-beta-D-xylofuranosyl)thiazole-4-carboxamide: a new tiazofurin analogue with potent antitumour activity.
A new tiazofurin analogue, 2-(3-amino-3-deoxy-beta-d-xylofuranosyl)thiazole-4-carboxamide (3), was synthesized starting from d-glucose and evaluated for its in vitro antiproliferative activityExpand
Synthesis and in vitro antitumour screening of 2-(β-D-xylofuranosyl)thiazole-4-carboxamide and two novel tiazofurin analogues with substituted tetrahydrofurodioxol moiety as a sugar mimic.
Flow cytometry data suggest that cytotoxic effects of analogue 2 in the culture of K562 cells might be mediated by apoptosis, in opposite to tiazofurin, which did not induce apoptosis of K561 cells after 24h, thus suggesting a different mechanism of action. Expand
2-Substituted thiazole-4-carboxamide derivatives as tiazofurin mimics: synthesis and in vitro antitumour activity
Abstract Tiazofurin analogues bearing a 5-hydroxymethyl-2-methyl-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol moiety as a sugar mimic (2 and 3), and two novel thiazole-based acyclo-C-nucleosides 4 and 16Expand
Synthesis of benzamide-C-ribonucleosides by Pd-catalyzed aminocarbonylations
Abstract A novel modular, efficient and practical methodology for preparation of p - and m -substituted benzamide- C -ribonucleosides was developed. Reaction of TBS-protected 3- and 4-bromophenyl- CExpand
Synthesis and Antitumor Activity of Some Novel Pyrazole and Thienopyrimidine Derivatives
The novel thiosemicarbazide derivative was prepared by hydrazinolysis of isothiocyanatosulfonamide with hydrazine hydrate. It was used as a starting material for the synthesis of some novelExpand
C-Nucleosides To Be Revisited.
Two new C-nucleoside analogues, BCX4430, an imino-C-nucleoside, and GS-6620, a phosphoramidate derivative of 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine C-nucleoside, have been recently describedExpand
Synthesis of highly cytotoxic tiazofurin mimics bearing a 2,3-anhydro function in the furanose ring
Abstract This paper describes a divergent de novo synthesis of 2-(2,3-anhydro-β- d -ribofuranosyl)thiazole-4-carboxamide (2′,3′-anhydro-tiazofurin) and the corresponding α- and β-homo-C-nucleosides.Expand
Synthesis, molecular structure, DFT studies and antimicrobial activities of some novel 3-(1-(3,4-dimethoxyphenethyl)-4,5-diphenyl-1H-imidazol-2-yl)-1H-indole derivatives and its molecular docking studies
A new series of 3-(1-(3,4-dimethoxyphenethyl)-4,5-diphenyl-1H-imidazol-2-yl)-1H-indole derivatives (5a-5j) are conveniently synthesized and characterized by IR, 1H NMR and 13C NMR spectralExpand


Furanfurin and thiophenfurin: two novel tiazofurin analogues. Synthesis, structure, antitumor activity, and interactions with inosine monophosphate dehydrogenase.
The results obtained support the hypothesis that the presence of S in the heterocycle in position 2 with respect to the glycosidic bond is essential for the cytotoxicity and IMP dehydrogenase activity of tiazofurin, while the N atom is not. Expand
Synthesis, structure, and antiproliferative activity of selenophenfurin, an inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin.
The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides. Expand
Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors.
Dinucleotides TFAD, FFAD, and SFAD, isosteric NAD analogues derived from C-nucleosides 5-beta-d-ribofuranosylthiophene-3-carboxamide, were synthesized as human inosine monophosphate dehydrogenase (IMPDH) type I and II inhibitors and evaluated for inhibitory potency. Expand
A new synthesis of some 4'-thio-D-ribonucleosides and preliminary enzymatic evaluation
Abstract A new synthesis of 4′-thioribonucleosides is presented together with the enzymatic evaluation of the adenosine analogues with respect to adenosine kinase. The 4-thio-D-ribofuranosylExpand
On the conformation of tiazofurin analogues.
Computational methods report that although the above interaction is likely to contribute to the low-energy conformation of these classes of molecules, the flexibility of the glycosylic bond is ultimately determined by steric interaction of the heteroatoms with the C2'-H and O4' of the ribose. Expand
Comparison of biochemical parameters of benzamide riboside, a new inhibitor of IMP dehydrogenase, with tiazofurin and selenazofurin.
It is demonstrated that selenazofurin was the most potent of the three agents, even though they share similar mechanisms of action, in terms of cytotoxic and biochemical actions. Expand
Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design.
The 2.9-A structure of a ternary complex of the human type II isoform of IMPDH is presented, suggesting strategies for the design of isoform-specific agents in antitumor and immunosuppressive drug design. Expand
4′-Thio-RNA: Synthesis, Base Pairing Properties and Interaction with Dimerization Initiation Site of HIV-1
Abstract in the present paper, we describe the synthesis of a modified 9-mer oligonucleotide, 4′-S-r(UGUGCACCU) containing for the first time 4′-thio-guanosine units. This modified 9-mer was found toExpand
Computational studies of nonbonded sulfur-oxygen and selenium-oxygen interactions in the thiazole and selenazole nucleosides
Computational studies have been performed to investigate the origin and magnitude of a biologically important nonbonded interaction: the sulfur-oxygen and selenium-oxygen interaction observed in theExpand
Density-functional thermochemistry. III. The role of exact exchange
Despite the remarkable thermochemical accuracy of Kohn–Sham density‐functional theories with gradient corrections for exchange‐correlation [see, for example, A. D. Becke, J. Chem. Phys. 96, 2155Expand