Planejamento racional de fármacos baseado em produtos naturais

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

Characterization of flavonoid and naphthopyranone derivatives from Eriocaulon ligulatum using liquid chromatography tandem mass spectrometry

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

Suppression of TNF- induced NFB activity by gallic acid and its semi-synthetic esters: possible role in cancer chemoprevention

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

Preparative isolation of a novel flavonoid from an infusion of Byrsonima basiloba leaves by high-speed counter-current chromatography

A method for the isolation of three compounds from the infusion of leaves of Byrsonima basiloba A. Juss. by high-speed counter-current chromatography (HSCCC) was developed. This technique led to the separation of a novel compound, quercetin 3-O-alpha-L-rhamnopyranosyl-(1 -> 3)-O-[alpha-L-rhamnopyranosyl-(1 -> 6)]-beta-D-allopyranoside, and two known compounds quercetin3-O-(X-L-rhamnopyranosyl-(1 -> 6)-beta-D-galactopyranoside and (+)-catechin in 4 h with purities of over 92%. The structures of the compounds were determined by one- and two-dimensional NMR spectroscopy and HPLC.

FTY720 prevents renal T-Cell infiltration after ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

Chemical evolution in the Asteraceae. The Oxidation-Reduction mechanism and production of secondary metabolites

This work describes the application of partial least squares (PLS) regression to variables that represent the oxidation data of several types of secondary metabolite isolated from the family Asteraceae. The oxidation states were calculated for each carbon atom of the involved compounds after these had been matched with their biogenetic precursor. The states of oxidation variations were named oxidation steps. This methodology represents a new approach to inspect the oxidative changes in taxa. Partial least square (PLS) regression was used to inspect the relationships among terpenoids, cournarins, polyacetylenes, and flavonoids from a data base containing approximately 27,000 botanical entries. The results show an interdependence between the average oxidation states of each class of secondary metabolite at tribe and sub tribe levels.

Triterpenes from Maytenus macrocarpa and evaluation of their anti-HIV activity

A set of pentacyclic triterpenes has been isolated from the bark of Maytenus macrocarpa (Celastraceae). It includes two new olean-12-ene derivatives, namely 3 beta, 22(alpha-dihydroxy-olean-12-en-30-oic acid (1) and 22 alpha-hydroxy-olean-12-en-3-oxo-30-oic acid (2), and the new urs-12-ene derivative 3-(E)-coumaroyluvaol (7), along with 10 known compounds possessing olean-12ene, urs-12-ene, lupane and friedelane skeletons. The structures have been elucidated by extensive spectroscopic methods including ID- and 2D-NMR experiments, as well as ESI-MS analysis. All isolated compounds were tested for anti-HIV activity in C8166 cells infected with HIV-1(MN), the most active compound was 22(alpha-hydroxy-12-en-3-oxo-29-oic acid (triterpenonic acid A, 4), with an EC50 value of I mu g/mL and a selectivity index of 35.

Isolation and chemical characterization of PwTx-II: A novel alkaloid toxin from the venom of the spider Parawixia bistriata (Araneidae, Araneae)

Brazil has many species of spiders belonging to Araneidae family however, very little is known about the composition, chemical structure and mechanisms of action of the main venom components of these spiders. The main objective of this work was to isolate and to perform the chemical characterization of a novel beta-carboline toxin from the venom of the spider Parawixia bistriata, a typical species of the Brazilian 'cerrado'. The toxin was purified by RP-HPLC and structurally elucidated by using a combination of different spectroscopic techniques (UV, ESI-MS/MS and H-1 NMR), which permitted the assignment of the molecular structure of a novel spider venom toxin, identified as 1-4-guanidinobutoxy-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, and referred to here as PwTx-II. This compound is toxic to insects (LD50 = 12 +/- 3 eta g/mg honeybee), neurotoxic, convulsive and lethal to rats (LD50 = 9.75 mg/kg of male Wistar rat). (c) 2005 Elsevier Ltd. All rights reserved.

K-ATP(+) Channels-Independent Analgesic Action of Crotalus durissus cumanensis venom

The effect was investigated of the K+ channel blocker, glibenclamide, on the ability of Crotalus durissus cumanensis venom (CDCM) to promote peripheral antinociception. This was measured by formalin-induced nociception in male Swiss mice. CDCM (200 and 300 mu g/kg) produced an antinociceptive effect during phase 2 in the formalin test. The effect of CDCM (200 mu g/kg) was unaffected by the ATP-sensitive K+ channel blocker glibenclamide (2 mg/kg). These results suggest that CDCM is effective against acute pain. However, the ATP-sensitive K+ channels pathway is not contributable to the antinoeiceptive mechanism of CDCM.

Cytotoxicity of Active Ingredients Extracted from Plants of the Brazilian "Cerrado"

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

Diagnosis of Public Programs focused on Herbal Medicines in Brazil

The present study is aimed to diagnose the current public programs focused on herbal medicines in Brazil by means of in loco visits to 10 programs selected by means of questionnaires sent to 124 municipalities that count on herbal medicine services. The main purpose of the implementation of program programs is related to the development of medicinal herbs. 70% of them are intended for the production of herbal medicines and 50% are aimed to ensure the access of the population to medicinal plants and or herbal medicines. The initiative of the implementation of these programs was related to the managers (60%). The difficulties in this implementation were due to the lack of funding (100%) of the programs. In 60% of the programs, the physicians did not adhere to herbal medicine services due to the lack of knowledge of the subject. Training courses were proposed (80%) to increase the adhesion of prescribers to the system. Some municipalities use information obtained from patients to assess the therapeutic efficiency of medicinal plants and herbal medicines. of the programs underway, cultivation of medicinal plants was observed in 90% and 78% of them adopt quality control. In most programs, this control is not performed in accordance with the legal requirements. The programs focused on medicinal plants and herbal medicines implemented in Brazil face sonic chronic problems of infrastructure, management, operational capacity and self-sustainability, which can be directly related to the absence of a national policy on medicinal plants and herbal medicines.

First record of L-quebrachitol in Allophylus edulis (Sapindaceae)

Allophylus edulis, commonly called 'Chal chal', is a member of the Sapindaceae occurring in the Uruguayan and Brazilian native flora. During the phytochemical analysis of two Chal chal specimens from two welldifferentiated geographical zones (Assis, São Paulo, Brazil, and Santa Lucia, Canelones, Uruguay), considerable amounts of L-quebrachitol were isolated from both samples. The isolation was carried out from the ethanolic twig extracts obtained by maceration of both vegetal samples. White easily distinguishable crystals were mechanically separated, washed, and characterized by 1D and 2D NMR experiments and by MS data. Such techniques confirmed that the crystals isolated from sources collected in both countries resulted in the same compound, L-quebrachitol, a natural product not previously reported for this species and one that has been investigated as a sugar substitute for diabetics. Worthy of note, the content of L-quebrachitol in A. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat diabetes in the practice of local traditional medicine. (c) 2008 Elsevier Ltd. All rights reserved.

Isocoumarin from Paepalanthus bromelioides

The new isocoumarin, 9,10-dihydroxy-5, 7-dimethoxy-1H-naphtho(2,3c)pyran-1-one, was isolated from the capitula of Paepalanthus bromelioides. The structure was established by means of the spectral data of the natural product and its derivatives. The natural isocoumarin isolated has strong antibiotic activity. © 1990.

Triterpenes and saponins from Rudgea viburnioides

A novel triterpene; viburgenin (1), has been isolated from an extract of the ripe fruit rinds of Rudgea viburnioides, together with the known saponins, arjunglucoside I and trachelosperosides B-1 and E-l, and the triterpenes trachelosperogenin B (2) and arjungenin. Compound 2 was previously obtained as a product from enzymatic hydrolysis, and it is reported for the first time as a natural product. The structure of compound 1 was determined as 2α,3β,19α,23,24-pentahydroxyurs-12-ene by extensive use of 1D and 2D NMR spectroscopic methods. Compound 1 exhibited moderate antifungal activity against Cladosporium cladosporioides.

A computer-assisted approach for chemotaxonomic studies - Diterpenes in Lamiaceae

This paper describes a new computer approach for chemotaxonomic studies. The methodology employed enables the search for chemical substructures as taxonomic descriptors using all expert system built with plant natural products. The operation of the system was tested with diterpenes as taxonomic markers in Lamiaceae. © 2001 Elsevier Science Ltd.