Synthesis of d-fructose conjugated ligands via C6 and C1 and their corresponding [Ru(bpy)2(L)]Cl2 complexes.

A pyridyl triazole (pyta) modified sucrose ligand was prepared in a seven step synthesis using d-glucose as the protection group for d-fructose and starting from commercially available sucrose. After complexation with Ru(bpy)2Cl2 precursor, the sucrose-conjugated Ru complex of the general formula [Ru(bpy)2(L)]Cl2 was formed. Acidic cleavage of the d-glucose unit led to the first d-fructose conjugated metal complex viad-fructose C6 in literature. Additionally, pyta-modified d-fructose via C1 and the corresponding Ru complex were synthesized. All compounds were analyzed by Rf values, specific rotation, NMR, IR, UV/Vis and fluorescence spectroscopy, mass spectrometry and elemental analysis.

Synthesis, Characterization, Antimicrobial and Antitumor Activities of Sucrose Octa(N-ethyl)carbamate.

Sucrose octa(N-ethyl)carbamate was synthesized directly from sucrose and ethyl isocyanate, and its structure was confirmed by various analytical methods, such as (1)H and (13)C NMR, FTIR, m.p., MS, and optical rotation. Its antibacterial, antifungal and cytotoxic activities were investigated. It exhibited strong inhibition against all bacteria tested, namely S. aureus (MIC 0.18±0.006), B. cereus (MIC 0.094±0.000), M. flavus (MIC 0.28±0.01), L. monocytogenes (MIC 0.18±0.006), P. aeruginosa (MIC 0.094±0.002), S. typhimurium (MIC 0.094±0.002), E. coli (MIC 0.18±0.006) and E. cloacae (MIC 0.18±0.006) and strong antifungal activity towards T. viride (MIC 0.09 ± 0.006), A. versicolor (MIC 0.18 ± 0.01), A. ochraceus (MIC 0.375 ± 0.01) and P. ochrochloron (MIC 0.375 ± 0.04). Furthermore, it showed moderate antitumor potential against human breast (GI50 357.20±14.12), colon (GI50 332.43±11.19) and cervical (GI50 282.67±3.97) cell lines and, more important, without hepatotoxicity.

Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives.

A library of 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-1,2,3-triazoles have been investigated for their antibacterial, antifungal and cytotoxic activities. Most of the target compounds showed good inhibitory activity against a variety of clinically and food contaminant important microbial pathogens. In particular, 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-pentylphenyl)-1,2,3-triazole (5) was highly active against all the tested bacteria with minimal inhibitory concentrations (MICs) ranging between 1.1 and 4.4 µM and bactericidal concentrations (MBCs) from 2.2 and 8.4 µM. The compound 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-bromophenyl)-1,2,3-triazole (3) showed antifungal activity with MICs from 0.6 to 4.8 µM and minimal fungicidal concentrations (MFCs) ranging between 1.2 and 8.9 µM. Furthermore, some of the compounds possessed moderate cytotoxicity against human breast, lung, cervical and hepatocellular carcinoma cell lines, without showing toxicity for non-tumor liver cells. The above mentioned derivatives represent promising leads for the development of new generation of sugar-triazole antifungal agents.

Synthesis and antiproliferative activity of helonioside A, 3',4',6'-tri-O-feruloylsucrose, lapathoside C and their analogs.

The first total synthesis of natural phenylpropanoid sucrose esters (PSEs) helonioside A 1, 3',4',6'-tri-O-feruloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSE analogs has been successfully accomplished in a short and simple synthetic route. A selected set of 17 synthesized PSEs were evaluated for the antiproliferative activity against human cervical epithelioid carcinoma (HeLa) cell lines using MTS assay method. Eleven (11) compounds showed significant antiproliferative activity with their IC(50)values ranging from 0.16 to 6.01 µM. The structure-activity-relationship studies revealed that the antiproliferative activity is influenced by the lipophilicity and number of feruloyl substituents on these compounds. The preliminary screening indicated that these compounds are potentially very valuable source for new lead chemotherapeutics.

Estudo comparativo da reação inflamatória de feridas tratadas com açucar com (sacarose) e compostos com ácidos graxos essenciais, em ratos: estudo preliminar / Comparative study about the inflammatory esponse of wounds treated with sugar (sucrose) and fatty acids compounds, in rats: preliminary study

Introdução: o tratamento de feridas tem recebido grande atenção, atualmente, como uso de novos produtos e o abandono de terapias tradicionais. Objetivo: Estudar a reação inflamatória de feridas tratadas com açúcar e solução de ácidos graxos essenciais. Métodos: em estudo aleatório foi criada uma ferida de 400mm 2, no dorso de ratos Wistar, tratadas com deposição diária de solução fisiológica de cloreto de sódio 0,9, no grupoA (n=32), açúcar no grupo B(n=32) e solução de ácidos graxos essenciais, nos animais do grupo C(n=32), com curativo oclusivo. As aferições foram realizadas no 3º, 7º, 14º e 20º dias de pós-operatório e a reação infamatória nas feridas dos animais foi quantificada através de análise histológica. Resultados: não houve diferença significante entre os grupos em estudo. Discussão: os resultados se mostraram equivalentes na modulação da resposta inflamatória dos animais estudados.Conclusões. Não houve diferença significante na reação inflamatória durante a cicatrização de feridas tratadas com açúcar e compostos de ácidos graxos essenciais, em ratos.

Background: the attempt for wounds treatment in our days include new therapies and discharge some traditional ones. Objective: the aim of this study is to evaluate the inflammatory response of wounds treated with sugar and fatty acids compouds. Methods: into this random study a 400 mm 2 scar was performed on the back of Wistar rats and treated with daily occluded dresses. Animals of group A (n=32) received saline solution on the scar, group B received sugar and group C received fatty acids solution. Measures were taken on 3 rd, 7 th, 14th e 20 th post operative days and the inflammatory response wase valuated byhistologicalanalysis. Results:t heresults show edequival entres ponseson inflammatory modulation of the studied animals. Conclusions: there were no differences on inflammatory response of wounds treated with sugar and fatty acids solution, in rats.

Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats.

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.

Synthesis of nitrosourea derivatives of sucrose as central nervous system anticancer agents.

Nitrosourea derivatives of sucrose have been synthesized for the purpose of obtaining anticancer agents with activity against brain cancer. Two such compounds, 6,6'-dideoxy-6,6'-di(3-methyl-3-nitrosoureido) sucrose (13) and 1', 6,6'-trideoxy-1',6,6-tri(3-methyl-3-nitrosoureido) sucrose (14), and their respective acetylated derivatives 15 and 16 have been prepared from sucrose. Compounds 13 and 14 have demonstrated antitumor activity against both L1210 leukemia and ependymoblastoma brain tumor in mice.