Structural bioinformatics study of cyclin-dependent kinases complexed with inhibitors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Flavonols from Pterogyne nitens and their evaluation as myeloperoxidase inhibitors

A myeloperoxidase inhibitory kaempferol derivative, namely pterogynoside (1), was isolated from fruits of Pterogyne nitens, along with six known flavonols, kaempferol, afzelin, kaempferitrin, quercetin, isoquercetrin and rutin. The structures of all compounds were elucidated primarily from 1D and 2D NMR spectroscopic analyses, as well as by high resolution mass spectrometry. All flavonols were screened to identify secondary metabolites as potential myeloperoxidase (MPO) inhibitors, and at concentrations of 0.50-50 nM, quercetin (5), isoquercitrin (6) and rutin (7) exhibited strong inhibitory effects with IC(50) values of 1.22 +/- 0.01, 3.75 +/- 0.02 and 3.60 +/- 0.02, respectively. The MPO activity detected for the new derivative 1 was markedly decreased (IC(50) 10.3 +/- 0.03) when compared with known flavonols 5-7, and interestingly increased when tested against ABTS scavenging activity. (C) 2008 Published by Elsevier Ltd.

Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Peptides based on CcdB protein as novel inhibitors of bacterial topoisomerases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effect of non-surgical periodontal therapy on peroxidase activity in diabetic patients: a case-control pilot study

Objective: To evaluate the effect of periodontal therapy on clinical parameters as well as on total salivary peroxidase (TSP) activity and myeloperoxidase (MPO) activity in the gingival crevicular fluid (GCF) of patients with type 2 diabetes mellitus (DM2) and of systemically healthy individuals.Material and Methods: Twenty DM2 subjects with inadequate metabolic control (test group) and 20 systemically healthy individuals (control group), both groups with chronic periodontitis, were enrolled. Periodontal clinical parameters, namely periodontal probing depth (PD), clinical attachment level (CAL), visible plaque index (VPI), bleeding on probing (BOP), gingival bleeding index (GBI) and presence of suppuration (SUP), as well as TSP activity and GCF MPO activity, were assessed before and 3 months after non-surgical periodontal therapy.Results: At baseline and 3 months post-treatment, the test group presented a higher percentage of sites with VPI and BOP (p < 0.01). MPO activity in the GCF presented lower values (p < 0.05) for the test group at both baseline and the post-treatment period. The periodontal treatment resulted in a significant improvement of most clinical and enzymatic parameters for both groups (p < 0.05).Conclusions: In both groups, the periodontal therapy was effective in improving most clinical parameters and in reducing salivary and GCF enzymatic activity. The diabetic individuals presented lower MPO activity in the GCF.

Design and synthesis of peptides from bacterial ParE toxin as inhibitors of topoisomerases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CNS-selective noncompetitive cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline

LASSBio-767 [(-)-3-O-acetyl-spectaline] and LASSBio-822 [(-)-3-O-tert-Boc-spectaline] were recently described as cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline, obtained from the flowers of Senna spectabilis (Fabaccae). We investigated their mechanism of inhibition of acetylcholinesterase and their efficacy in reversing scopolamine-induced amnesia. Competition assays with the substrate acetylthiocholine showed a concentration-dependent reduction in rat brain cholinesterase V-max without changes in apparent K-m. The kinetic data for LASSBio-767 and LASSBio-822 were best fit by a model of simple linear noncompetitive inhibition with K-i of 6.1 mu M and 7.5 mu M, respectively. A dilution assay showed a fast and complete reversal of inhibition, independent of incubation time. Simulated docking of the compounds into the catalytic gorge of Torpedo acetylcholinesterase showed interactions with the peripheral anionic site, but not with the catalytic triad. Anti-amnestic effects in mice were assessed in a step-down passive avoidance test and in the Morris water maze 30 min after injection of scopolamine (1 mg/kg i.p.). Saline, LASSBio-767, or LASSBio-822 was administered 15 min before scopolamine. Both compounds reversed the scopolamine-induced reduction in step-down latency at 0.1 mg/kg i.p. LASSBio-767 reversed scopolamine-induced changes in water maze escape latency at 1 mg/kg i.p. or p.o., while its cholinergic side effects were absent or mild up to 30 mg/kg i.p. (LD50 above 100 mg/kg i.p.). Thus, the (-)-spectaline derivatives are potent cholinergic agents in vivo, with a unique profile combining noncompetitive cholinesterase inhibition and CNS selectivity, with few peripheral side effects. (C) 2007 Elsevier B.V. All rights reserved.

Pyridine Alkaloids from Senna multijuga As Acetylcholinesterase Inhibitors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular Docking and Molecular Dynamic Studies of Semi-Synthetic Piperidine Alkaloids as Acetylcholinesterase Inhibitors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito comparativo do calor, S0(2) e ácido ascórbico na atividade da polifenol oxidase e peroxidase de algumas frutas e hortaliças

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Callus cell culture of Pothomorphe umbellata (L.) under stress condition leads to high content of peroxidase enzyme

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo do comportamento eletroquímico da enzima peroxidase na presença de peróxido de hidrogênio e ácido 5-aminossalicílico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Inhibitors of Clostridium histolyticum colagenase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)