Exploitation of new structurally diverse d-glucuronamide-containing N-glycosyl compounds: synthesis and anticancer potential. 2017

Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, 5° Piso, Campo Grande, 1749-016 Lisboa, Portugal. nmxavier@fc.ul.pt.

The synthesis and anticancer evaluation of novel N-glycosyl derivatives containing N-substituted glucuronamide moieties, as nucleoside analogs or as prospective mimetics of glycosyl phosphates or of nucleotides, is reported. These compounds comprise N-anomerically-linked nucleobases or motifs that are surrogates of a phosphate group, such as sulfonamide or phosphoramidate moieties. 1-Sulfonamido glucuronamides containing N-benzyl, N-propargyl or N-dodecyl carboxamide units were synthesized through glycosylation of methanesulfonamide with tetra-O-acetyl glucuronamides. 1-Azido glucuronamides were accessed by microwave-assisted reactions of tetra-O-acetyl glucuronamides with TMSN3 and were further converted into N-glycosylphosphoramidates by treatment with trimethyl phosphite. Potential glucuronamide-based nucleotide mimetics comprising both an anomeric sulfonamide/phosphoramidate group and a benzyltriazolylmethyl amide system at C-5, as nucleobase mimetics, were synthesized via 'click' cycloaddition of N-propargyl glucuronamide derivatives with benzyl azide. N-Dodecyl tetra-O-acetyl glucuronamides were converted into uracil and purine nucleosides via N-glycosylation of the corresponding silylated nucleobases. Biological screening revealed significant antiproliferative activities of the N-dodecyl glucuronamide-containing sulfonamide, phosphoramidate and nucleosides in K562 and MCF-7 cells. The highest effect was exhibited by the N9-linked purine nucleoside in the breast cancer cell MCF-7 with a GI50 value similar to that of clinically used 5-fluorouracil. Immunoblotting and cell cycle analysis of K562 cells treated with the most active compound as well as evaluation of the effect of this nucleoside on the activities of caspases 3 and 7 showed induction of apoptosis as the mechanism of cell death.

UI MeSH Term Description Entries
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D060326 Chemistry Techniques, Synthetic Methods used for the chemical synthesis of compounds. Included under this heading are laboratory methods used to synthesize a variety of chemicals and drugs. Inorganic Synthesis,Inorganic Synthesis Methods,Inorganic Synthesis Techniques,Methods of Inorganic Synthesis,Methods of Organic Synthesis,Methods of Peptide Synthesis,Organic Synthesis,Organic Synthesis Methods,Organic Synthesis Techniques,Peptide Synthesis Methods,Peptide Synthesis Techniques,Peptide Synthesis, Synthetic,Synthetic Chemistry Techniques,Synthetic Peptide Synthesis,Chemistry Technique, Synthetic,Inorganic Syntheses,Inorganic Synthesis Method,Inorganic Synthesis Technique,Method, Inorganic Synthesis,Method, Organic Synthesis,Method, Peptide Synthesis,Methods, Inorganic Synthesis,Methods, Organic Synthesis,Methods, Peptide Synthesis,Organic Syntheses,Organic Synthesis Technique,Peptide Syntheses, Synthetic,Peptide Synthesis Method,Peptide Synthesis Technique,Syntheses, Inorganic,Syntheses, Organic,Syntheses, Synthetic Peptide,Synthesis Method, Inorganic,Synthesis Method, Peptide,Synthesis Methods, Inorganic,Synthesis Methods, Peptide,Synthesis Technique, Inorganic,Synthesis Technique, Organic,Synthesis Technique, Peptide,Synthesis Techniques, Inorganic,Synthesis Techniques, Organic,Synthesis Techniques, Peptide,Synthesis, Inorganic,Synthesis, Organic,Synthesis, Synthetic Peptide,Synthetic Chemistry Technique,Synthetic Peptide Syntheses,Technique, Inorganic Synthesis,Technique, Organic Synthesis,Technique, Peptide Synthesis,Technique, Synthetic Chemistry,Techniques, Inorganic Synthesis,Techniques, Organic Synthesis,Techniques, Peptide Synthesis,Techniques, Synthetic Chemistry
D061986 MCF-7 Cells An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.) MCF7 Cells,Michigan Cancer Foundation 7 Cells,Cell, MCF-7,Cell, MCF7,Cells, MCF-7,Cells, MCF7,MCF 7 Cells,MCF-7 Cell,MCF7 Cell
D020014 K562 Cells An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS. Cells, K562

Related Publications

Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
March 1965, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
November 2002, Carbohydrate research,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
September 2017, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
January 1966, Yao xue xue bao = Acta pharmaceutica Sinica,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
January 2008, Current topics in medicinal chemistry,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
May 1982, Journal of pharmaceutical sciences,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
November 1994, Die Pharmazie,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
June 1994, Bollettino chimico farmaceutico,
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
August 2014, Angewandte Chemie (International ed. in English),
Nuno M Xavier, and Alexandre Porcheron, and Daniela Batista, and Radek Jorda, and Eva Řezníčková, and Vladimír Kryštof, and M Conceição Oliveira
September 2019, Bioorganic chemistry,
Copied contents to your clipboard!