Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Hematological responses of tambaqui Colossoma macropomum (Serrassalmidae) fed with diets supplemented with essential oil from Mentha piperita (Lamiaceae) and challenged with Aeromonas hydrophila

ABSTRACTIn fish farmings, diseases can be reduced by using immunostimulants. The aim of this study was to evaluate the immunostimulant potential of Mentha piperita in tambaqui fed with 0, 0.5, 1.0 and 1.5% of oil per kg of commercial fish feed. The fish were inoculated with Aeromonas hydrophila to challenge them. Hematological and biochemical parameters were determined after 30 days of feeding and seven days after the challenge. There was no mortality and M. piperita oil did not influence fish production parameters. However, blood hemoglobin concentration (Hb) increased in the fish fed with 0.5 and 1.5% of oil per kg of diet; albumin increased in those fed with 1.0%; cholesterol increased in all groups with oil; and triglycerides increased in those fed with 0.5%. After the bacterial challenge, the fish showed decreases in Hb when fed with diet enriched with 1.5% oil per kg of diet, in mean corpuscular volume with 1.0% and in mean corpuscular hemoglobin concentration with 0 and 1.5%. Protein levels increased in groups with 0 and 1.5% of oil and albumin when fed with 0 and 1.0%; cholesterol levels increased in the control group; and high levels of triglycerides were observed in the groups with 0, 0.5 and 1.5%. Thus, M. piperita essential oil promoted hematological alterations in tambaqui and can be recommended in diets containing up to 1.0% per kg, because of the minimal physiological modifications caused. However, additional studies are necessary to obtain more information regarding to the physiological effects of this immunostimulant.

In vivo antileishmanial activity and chemical profile of polar extract from Selaginella sellowii

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.

Compostos de platina em quimioterapia do câncer

The vast majority of clinically used antitumor drugs are either synthetic or natural product based organic compounds. In this review we describe different aspects, such as structure-activity relationships, mechanism of action, clinical uses and possible future prospects, of the platinum antitumor complexes, a distinct class of antitumor agents.

A utilização do safrol, principal componente químico do óleo de sassafráz, na síntese de substâncias bioativas na cascata do ácido araquidônico: antiinflamatórios, analgésicos e anti-trombóticos

In this paper we describe the results of a research effort developed in Laboratório de Avaliação e Síntese de Substancias Bioativas (LASSBio, UFRJ) in the utilization of Brazilian abundant natural product, safrole (1), the principal chemical constituent of Sassafras oil (Ocotea pretiosa), as an attractive synthon to access different chemical class of bioactive compounds, as prostaglandins analogues, non-steroidal antiinflammatory agents and antithrombotic compounds.

Gênero Physalis - uma revisão sobre vitaesteróides

This review describes results on the chemistry and spectroscopic data of some ergostane derivatives named withasteroids which have been obtained from Physalis genus. The main aim of this report is concerned with the description and characterization of Physalins. These natural product substances are C28 seco steroid lactone type compounds that have been shown biological activities against human illness such as immuno-deficiency, neoplasic tumors, inflammatory process and tropical endemic diseases. Physalins appear to be a source for new drugs to be apply as medicine.

Estado da arte da cromatografia gasosa de alta resolução e alta temperatura

The developments in stationary phase synthesis and capillary column technology, have opened new perspectives in analysis of high molecular mass compounds (³600 daltons) and thermolabile organic compounds by High Temperature High Resolution Gas Chromatography (HT-HRGC). HT-HRGC is a new analytical borderline and its application to the analysis of high molecular mass compounds is still in its infancy. The apolar and medium polar gum phases can now be operated at temperatures up to 400-480ºC, being used for the analysis of n-alcanes up to C-100, lipids, oligosaccharides, industrial resins, polyglycerols, cyclodextrins, porphyrins, etc. This technique should play a leading role as a powerful tool, for many different analysis types, in multidisciplinary fields of Science.

Planejamento racional de fármacos baseado em produtos naturais

In the area of drug discovery, natural products represent a myriad of templates for new lead discovery. It is, however, most unlikely that the bioactive principle itself shall become a drug; it is much more likely that a medicinal chemistry project needs to be initiated as soon the potency or selectivity or specificity of the new natural product candidate has been disclosed. Brazil has an enormous biodiversity where just a few has been disclosed. Nevertheless, it urges to initiate a joint collaboration in order to circumvent a major breakdown linking between natural products and medicinal chemistry in this country. This paper is intended to encourage people to follow up one of the most pushing forward enterprise that needs to be settled: the pharmaceutical industry.

Preparation and phytotoxicity of sorgoleone analogues

3,5-Dimethoxybenzylic alcohol was converted into the 2-acetoxy-5-methoxy-3-(pent-1-yl)-1,4-benzoquinone (12), in seven steps, with an overall yield of 14.6%. The natural quinone sorgoleone (1) was isolated from Sorghum bicolor and converted into the corresponding quinone (13) having a saturated side chain. The selective effects of these compounds (1, 12 and 13), at the dose of 5.6 mug of a.i./ g of substrate, on the growth of Cucumis sativus, Lactuca sativa, Desmodium tortuosum, Hyptis suaveolens and Euphorbia heterophylla were evaluated. All three compounds caused some inhibition on the root growth of the test plants (0.0-69.19%) with the aerial parts less affected. The results showed that the triene unit of the sorgoleone side chain is not essential for the phytotoxicity and also the synthetic quinone was as active as the natural product.

Estratégia de simplificação molecular no planejamento racional de fármacos: a descoberta de novo agente cardioativo

In this article are described examples of the successful use of molecular simplification strategy in the discovery of new drugs from bioactive natural products and synthetic compounds. The discovery of a new cardiotonic derivative (37, 2-thienylidene-3,4-methylenedioxybenzoylhydrazine; LASSBio-294), efficiently synthesized from Brazilian natural product and structurally designed by molecular simplification of active pyridazinone compounds reported in the literature, is described. A brief description of the pharmacological profile of this new cardiotonic lead-compound, belonging to the N-acylhydrazone (NAH) class, is also reported herein.

Um olhar holístico sobre a química de produtos naturais brasileira

This paper describes a comparative analysis on natural product chemistry between the Brazilian Chemical Society journals and twelve representative international publications in the area. The search using the ISI Web of Knowledge disclosed 41,362 publications in the years 2000-2002 containing at least one researcher from a Brazilian Institution, from which 12% belongs to natural products.

Novos produtos naturais capazes de atuar na estabilização de microtúbulos, um importante alvo no combate ao câncer

Microtubules are involved in many aspects of cellular biology and represent an important target of anticancer chemotherapeutics. In the past five years, novel natural products such as epothilones, discodermolide, sarcodictyin, eleutherobin, and laulimalide, all of which have biological activities similar to those of paclitaxel (Taxolâ), have been discovered. Taxolâ is an important antitumor drug approved by the FDA for the treatment of ovarian, breast and non-small-cell lung carcinomas and became the first natural product described that stabilized microtubules avoiding the cellular replication. The present article reports new natural products that are able to act on the stabilization of microtubules.

Constituintes químicos e atividade antioxidante de Sida galheirensiS Ulbr. (Malvaceae)

The phytochemical investigation of Sida galheirensis led to the isolation of 5,4'-dihydroxy-3,7,3´-trimethoxyflavone, 17³-ethoxyphaeoforbide, a rare natural product, 6,7-dimethoxycoumarin, ortho-hydroxybenzoic acid, sitosterol-3-O-beta-D-glucopyranoside, stigmasterol-3-O-beta-D-glucopyranoside, 5,7,4'-trihydroxyflavone, 5,7,3',4'-tetrahydroxyflavone, kaempferol-3-O-beta-D-(6"-E-p-coumaroyl) glucopyranoside and luteolin 7-O-beta-D-glucopyranoside. Their structures were assigned based on spectroscopic analyses, including two-dimensional NMR techniques. Antioxidant activities of hexane, CHCl3, EtOAc, BuOH and EtOH extracts of Sida galheirensis were measured using the 1,2-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay. This is also the first work reporting the chemical investigation of Sida galheirensis.

Espectroscopia de Ressonância Magnética Nuclear de 13C no estudo de rotas biossintéticas de produtos naturais

During the last five decades, as a result of an interaction between natural product chemistry, synthetic organic chemistry, molecular biology and spectroscopy, scientists reached an extraordinary level of comprehension about the natural processes by which living organisms build up complex molecules. In this context, 13C nuclear magnetic resonance spectroscopy, allied with isotopic labeling, played a determinant role. Nowadays, the widespread use of modern NMR techniques allows an even more detailed picture of the biochemical steps by accurate manipulation of the atomic nuclei. This article focuses on the development of such techniques and their impact on biosynthetic studies.

Biologia química: uma estratégia moderna para a pesquisa em produtos naturais

This paper presents an overview of the Natural Products Research in Brazil in the last five years (2002-2006), and also discusses how some relevant aspects of the Chemical Biology area could create new research opportunities and challenges for the natural product chemists. In addition, some aspects of the scientific policies and their impact on current projects are discussed.