RESUMO
The synthesis of 1-[5-O-(α-D-galactopyranosyl)-D-glucityl]pyrimidine-2,4(3H)-dione and 1-[(5-O-(ß-D-galactopyranosyl)-D-glucityl]pyrimidine-2,4(3H)-dione as non-ionic substrate mimics of UDP-Galp are described. UDP-Galp is a precursor of Galf, which is a primary component of the cell-wall glycans of several microorganisms. The interconversion of UDP-Galp and UDP-Galf is catalyzed by UDP galactopyranose mutase (UGM); its inhibition comprises a mode of compromising the microorganisms. The nonionic polyhydroxylated chain was intended to mimic the ionic pyrophosphate group and the ribose moiety in UDP-Galp and increase the bioavailabilities of the candidate inhibitors. Inhibition assays with UGM of Mycobacterium tuberculosis showed only weak inhibition of the enzyme by these compounds.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Galactose/metabolismo , Transferases Intramoleculares/antagonistas & inibidores , Monossacarídeos/farmacologia , Difosfato de Uridina/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Transferases Intramoleculares/metabolismo , Conformação Molecular , Monossacarídeos/síntese química , Monossacarídeos/química , Mycobacterium tuberculosis/enzimologia , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: The intestinal permeability (IP) of sugars and their derivatives has been widely used to assess mucosal damage in gastrointestinal diseases. Ulcerative colitis (UC) is a recurring and relapsing disease that causes inflammation of the gut. IP of sugars can be evaluated and correlated with the flare of UC. MATERIALS AND METHODS: A prospective study was conducted on 91 patients with active UC at the tertiary care center in North India. Mayo grading system assessed disease activity, and IP was assessed by measuring sucrose, lactulose, mannitol, and sucralose in urine samples from UC patients. A high-performance liquid chromatography (HPLC) method to detect all of these sugars simultaneously using a refractive index detector was developed and further validated in patients with UC. RESULTS: The analytical recovery rate of the tested sugars ranged from 95% to 146% in the urine matrix. The limit of detection and limit of quantification were 78.838 mg/L and 262.79 mg/L for sucrose, 84.994 mg/L and 283.31 mg/L for lactulose, 74.789 mg/L and 249.30 mg/L for mannitol, and 50.908 mg/L and 169.69 mg/L for sucralose. CONCLUSION: The standardized HPLC method is sensitive and suitable for the simultaneous detection and determination of different sugar moieties in the urine sample. Patients with UC can be evaluated indirectly for the flare by estimating the recovery rate of sugars through gut permeability. The procedure is noninvasive and thus improves the quality of life of chronically ill patients.
Assuntos
Colite Ulcerativa , Lactulose , Cromatografia Líquida de Alta Pressão/métodos , Colite Ulcerativa/tratamento farmacológico , Humanos , Absorção Intestinal , Lactulose/urina , Manitol , Permeabilidade , Estudos Prospectivos , Qualidade de Vida , Refratometria , Sacarose/análogos & derivados , Sacarose/urinaRESUMO
A series of galactose-derived aryl enones were synthesised and screened against Mycobacterium tuberculosis H(37)Rv. Preliminary results were promising with MIC values in the range 1.56-12.5 µg/mL.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/química , Galactose/síntese química , Galactose/química , Galactose/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piranos/síntese química , Piranos/química , Piranos/farmacologia , Relação Estrutura-AtividadeRESUMO
The use of iodine-DDQ as a promoter for glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with phenylseleno 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranoside in toluene-dioxane gave 49% and 73% yields, respectively, of the corresponding alpha-glycosides as the sole glycoside products. Reductive acetylation of the azide groups and cleavage of the benzyl esters by hydrogenolysis gave building blocks that were used in solid-phase synthesis to prepare triglycosylated tetrapeptides (Ac(3)GalNAc-alpha-Ser)(3)-Gly and (Ac(3)GalNAc-alpha-Thr)(3)-Gly in 27% and 49% overall yield, respectively.
Assuntos
Aminoácidos/química , Glicopeptídeos/síntese química , Glicosilação , Iodo/química , Acetilgalactosamina/análogos & derivados , Mucinas/química , Serina/análogos & derivados , Serina/química , Treonina/análogos & derivados , Treonina/químicaRESUMO
Methanol dried extensively over molecular sieves, or methanol in combination with powdered molecular sieves, serves as a good acceptor for acyl transfer reactions. Several O-acetylated and O-benzoylated sugar derivatives were efficiently de-O-acylated using this approach. In the case of per-O-acetylated N-acetylglucosamine, selective anomeric deprotection could be effected in high yield.
Assuntos
Carboidratos/química , Química Orgânica/métodos , Metanol/química , Acetilação , Acilação , Estrutura MolecularRESUMO
Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding beta-glycosides in good yields (64 and 62%, respectively). Direct coupling of the commercially available Fmoc-Ser-OH and Fmoc-Thr-OH carboxylic acids under similar conditions gave the corresponding beta-glycosides, possessing free carboxyl groups, in moderate yields (50 and 40%, respectively).
Assuntos
Benzeno/química , Glucosídeos/síntese química , Serina/química , Treonina/química , Brometos/química , Ácidos Carboxílicos/química , Ésteres , Dicloretos de Etileno/química , Glicosilação , Mercúrio/química , Estrutura MolecularRESUMO
Chiral nitroimidazoles were synthesized using sugars as the chiral source. The synthesized compounds showed promising antimycobacterial property with MIC value in the range 6.25-12.5µg/mL against Mycobacterium tuberculosis H(37)Rv.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Nitroimidazóis/síntese química , Nitroimidazóis/farmacologia , Antibacterianos/química , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Nitroimidazóis/químicaRESUMO
A series of galactose-linked nitroimidazoles/triazoles were synthesised and screened against Mycobacterium tuberculosis H(37)Rv. Preliminary results were promising with MIC values in the range 1.56-12.5 µg/mL. Most importantly they are active under aerobic condition under which metronidazole is inactive.
Assuntos
Galactose/química , Mycobacterium tuberculosis/efeitos dos fármacos , Nitroimidazóis/síntese química , Nitroimidazóis/farmacologia , Triazóis/síntese química , Triazóis/farmacologia , Testes de Sensibilidade Microbiana , Nitroimidazóis/química , Triazóis/químicaRESUMO
Treatment of peracetylated alkyl and aryl 1,2-trans-glycosides with iodine in the presence of HMDS has been found to result in the anomerization leading to the formation of the respective 1,2-cis-glycosides. In the case of alkyl glycosides with aglycons of short alkyl chain length complete anomerization to the alpha-glycosides was observed while with those of longer chain length the process was found to be incomplete. The observations have been interpreted mechanistically.