Ricardo José Alves

Friedelane and oleanane triterpenoids from bark wood ofAustroplenckia populnea

Abstract The bark wood of Austroplenckia populnea afforded, in addition to 3-hydroxy-2-oxofriedelan- 3-ene-20α-methylcar☐ylate, methyl populnonate, 3-hydroxy-2-oxofriedelan-3-ene-20α-car☐ylic acid, populnonic acid, epikatonic acid, dispermoquinone, β-sitosterol, β-sitostenone and dulcitol, two new pentacyclic triterpenes: 3-oxoolean-12-ene-20α-car☐ylic acid and 3β-hydroxy-2- oxofriedelan-20α-car☐ylic acid. The structures of these have been established from spectral studies and structural correlations, and single-crystal X-ray analysis of 3β-hydroxy-2-oxofriedelan- 20α-car☐ylic acid.

Lectin-based drug design: combined strategy to identify lead compounds using STD NMR spectroscopy, solid-phase assays and cell binding for a plant toxin model.

The growing awareness of the sugar code—i.e. the biological functionality of glycans—is leading to increased interest in lectins as drug targets. The aim of this study was to establish a strategic combination of screening procedures with increased biorelevance. As a model, we used a potent plant toxin (viscumin) and lactosides synthetically modified at the C6/C6′ positions and the reducing end aglycan. Changes in the saturation transfer difference (STD) in NMR spectroscopy, applied in inhibition assays, yielded evidence for ligand activity and affinity differences. Inhibitory potency was confirmed by the blocking of lectin binding to a glycoprotein‐bearing matrix. In cell‐based assays, iodo/azido‐substituted lactose derivatives were comparatively active. Interestingly, cell‐type dependence was observed, indicating the potential of synthetic carbohydrate derivative to interact with lectins in a cell‐type (glycan profile)‐specific manner. These results are relevent to research into human lectins, glycosciences, and beyond.

Synthesis and biodistribution studies of carbohydrate derivatives radiolabeled with technetium-99m

Three carbohydrate derivatives, MAG(3)-Gl, MAG(3)-Ga, MAG(3)-NG, were synthesized and radiolabeled in high yields. These substances were injected in health Swiss mice and their biodistribution were evaluated. Among them, (99m)Tc-MAG(3)-Ga displayed higher accumulation in hepatic tissue, due to the presence of specific receptors in the liver for this carbohydrate. Thus, the use of (99m)Tc-MAG(3)-Ga to assess hepatic function can be considered.

A novel d-glucose derivative radiolabeled with technetium-99m: Synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies and scintigraphic images in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Thus, d-glucose-MAG(3) could be considered as agent for tumor diagnosis.

Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain, cruzain and Schistosoma mansoni cathepsin B1

ABSTRACT The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series.

Synthesis and biological evaluation of technetium-labeled D-glucose-MAG3 derivative as agent for tumor diagnosis.

A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio and moderate tumor-to-blood ratio. Thus, d-glucose-MAG(3) is a potential agent for tumor diagnosis.

Effect of metronidazole analogues on Giardia lamblia cultures

We comparatively evaluate the effect of metronidazole (MTZ) and its five analogues on trophozoites of Giardia lamblia axenically growing. The compounds MTZ-Ms, MTZ-I, MTZ-Br, MTZ-N3, and MTZ-NH3Cl were obtained by molecular modification of the side chain of MTZ. Four of them presented higher giardicidal activity when compared with MTZ. Among them, MTZ-Br and MTZ-I were the most active, without cytotoxic effects against mitogen-activated human peripheral blood mononuclear cells (PBMC). The alteration of MTZ side chain constitutes a fruitful field to develop new drugs for the treatment not only of giardiasis but also of other diseases and signalize that metronidazole analogues are promising candidates as giardicidal and should be further evaluated.

Agentes antineoplásicos biorredutíveis: uma nova alternativa para o tratamento de tumores sólidos

A problem often encountered in cancer therapy is the presence of tumor cell subpopulation that are resistant to treatment. Solid tumors frequently contain hypoxic cells that are resistant to killing by ionizing radiation and also by many chemotherapeutic agents. However, these hypoxic cells can be exploited for therapy by non-toxic hypoxic-activated prodrugs. Bioreductive drugs require metabolic reduction to generate cytotoxic metabolites. This process is facilitated by appropriate reductases and the lower oxygen conditions present in solid tumors. The unique presence of hypoxic cells in human tumors provides an important target for selective cancer therapy.

In vitro evaluation of the activity of aromatic nitrocompounds against Trypanosoma cruzi

Fourteen compounds were evaluated for their activity against Trypanosoma cruzi blood stream forms at the concentration of 500 g/ml. Six compounds were active and re-tested at lower concentrations.

On the investigation of hybrid quinones: synthesis, electrochemical studies and evaluation of trypanocidal activity

In our continued search for novel trypanocidal compounds, arylamine, chalcone, triazolic, triazole– carbohydrate and chalcogenium derivatives containing a naphthoquinone scaffold were prepared; in addition to electrochemical studies, these compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Among the thirty-eight compounds herein evaluated, six were found to be more potent against trypomastigotes than the standard drug benznidazole, with IC50/24 h values between 52.9 and 89.5 mM.