title: Novel hydroxyamides and amides containing D-glucopyranose or D-fructose units: Biological assays in MCF-7 and MDST8 cell lines.
abstract: A novel library of 15 compounds, hydroxyamides and amides containing a β-D-glucopyranose (D-Gluc) or a β-D-fructose (D-Fruc) units was designed and synthesized for antiproliferative assays in breast (MCF-7) and colon (MDST8) cancer cell lines. Twelve of them were hydroxyamides and were successfully synthesized from β-D-glucuronic acid (D-GluA). Six of these hydroxyamides which were acetylated hydroxy-β-D-glucopyranuronamide 2a-2f (1st Family) and the other six were their respective isomers, that is, hydroxy-β-D-fructuronamide 3a-3f (2nd Family), obtained by acid-base catalyzed isomerization. These compounds have the general structure, D-Gluc-C=ONH-CHR-(CH2)n-OH and D-Fruc-C=ONH-CHR-(CH2)n-OH, where R=an aromatic, alkyl or a hydrogen substituent, with n=0 or 1. Eight of these contained a chiral aminoalcohol group. Three compounds were amides containing a D-glucopyranose unit (3rd Family). SAR studies were conducted with these compounds. Antiproliferative studies showed that compound 4a, the bromo-amide containing the β-D-glucopyranose ring, potently inhibits the proliferation of the MDST8 cells. Five compounds (2e, 2f, 3d, 3e, and 3f) were shown to potently selectively inhibit the proliferation of the MCF-7 cells. Compound 4b was the only one showing inhibition in both cell lines. In general, the more active compounds were the amides and hydroxyamides containing the β-D-fructose moiety, and containing an alkyl group or hydrogen. Half-inhibitory concentrations (IC50) of between 0.01 and 10 μM, were observed.
authors.affiliation: Centro de Química de Évora, IIFA, Universidade de Évora, Colégio L.A. Verney, 7000 Évora, Portugal. Electronic address: bete_carreiro@yahoo.com.
authors.forename: Elisabete P
authors.initials: EP
authors.lastname: Carreiro
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal; Instituto de Ciências Agrarias e Ambientais Mediterrânicas (ICAAM), Apartado 94, 7002-554 Universidade de Évora, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Costa
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Cordeiro
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Martins
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
authors.forename: Tiago O
authors.initials: TO
authors.lastname: Pires
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Saraiva
authors.affiliation: Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal; Instituto de Ciências Agrarias e Ambientais Mediterrânicas (ICAAM), Apartado 94, 7002-554 Universidade de Évora, Portugal; Center For Neurosciences and Cell Biology, University of Coimbra, Portugal.
authors.forename: Célia M
authors.initials: CM
authors.lastname: Antunes
authors.affiliation: Centro de Química de Évora, IIFA, Universidade de Évora, Colégio L.A. Verney, 7000 Évora, Portugal; Departamento de Química, Universidade de Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Burke
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005632:Fructose / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D061986:MCF-7 Cells; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D005632:Fructose; D005947:Glucose
keywords: Anti-tumor; Hydroxyamides; MCF-7; MDST8; d-Glucuronic acid