Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity.

The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC = 0.

Structure based design, synthesis and in vitro antitumour activity of tiazofurin stereoisomers with nitrogen functions at the C-2' or C-3' positions.

Three novel tiazofurin analogues having d-arabino stereochemistry and nitrogen functionalities at the C-2' position (5-7) have been designed and synthesized in multistep sequences, starting from d-glucose. The known d-xylo stereoisomer of 1 (compound 2) along with two new analogues bearing nitrogen functions at the C-3' (3 and 4) has also been synthesized from the same sugar precursor. The synthetic sequence consisted of the following three stages: (i) the multistep synthesis of suitably protected pentofuranosyl cyanides, (ii) the construction of ethyl thiazole-4-carboxylate part by cyclocondensation of thus obtained glycofuranosyl cyanides with l-cysteine ethyl ester followed by dehydrogenation, and (iii) the final transformation of the ethyl thiazole-4-carboxylates into the target tiazofurin analogues using the esters ammonolysis.

Synthesis and in vitro antitumour activity of tiazofurin analogues with nitrogen functionalities at the C-2' position.

Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose. A number of potential bioisosteres of 1 bearing acylamido functions at the C-2' position have also been synthesized from the same sugar precursor. In vitro cytotoxicities of target molecules against a number of human tumour cell lines were recorded and compared with those observed for lead molecule 1.

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.

2-(β-D-xylofuranosyl)thiazole-4-carboxamide (2) and two new tiazofurin analogues with 5-hydroxymethyl-2-methyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-ol moiety as a sugar mimic (27 and 28) have been synthesized and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines (K562, HL 60, Jurkat, Raji and HeLa). In contrast to previous literature reports, a metabolic MTT assay revealed remarkable cytotoxicity of 2 against K562 (IC(50)=0.15 μM) and HL-60 (IC(50)=0.

Synthesis and antitumour activity of new tiazofurin analogues bearing a 2,3-anhydro functionality in the furanose ring.

This paper describes a divergent de novo synthesis of 2-(2,3-anhydro-beta-dribofuranosyl)thiazole-4-carboxamide (2',3'-anhydro-tiazofurin) and the corresponding alpha- and beta-homo-C-nucleosides, as well as evaluation of their antitumour activities in vitro.

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 activity against a panel of human tumour cell lines. Compound 3 exhibited the most powerful cytotoxicity against K562 cells, being approximately 100-fold more potent than tiazofurin. This analogue was also active against Jurkat, HT-29 and HeLa malignant cells, with respective IC(50) values being ca.

Synthesis and antiproliferative activity of two new tiazofurin analogues with 2'-amido functionalities.

Two novel tiazofurin analogues 2 and 3 were synthesized starting from d-glucose. The key step of the synthesis was the efficient one-step hydrogen sulfide-mediated conversion of 2-azido-3-O-acyl-ribofuranosyl cyanides to the corresponding 2-amido thiocarboxamides. Compounds 2 and 3 were evaluated for their in vitro antiproliferative activity against certain human tumour cell lines.