Lysozyme inactivation by free radicals can occur independently of reactive carbonyl formation

The relationship between the free radical-induced loss of lysozyme activity and the occurrence of oxidative modifications, evidenced as gain in DNPHreactive carbonyl groups (CO) and loss of tryptophan-associated fluorescence (TAF), was addressed in vitro.2,2'-azobis (2-amidino propane)(20 raM, AAPtt) and a mixture of Fe+2/Ascorbate (Fe+2/A, 0.1/25 mM) were used as peroxyl and oxygen-de rived free radical sources. Lysozyme incubated (2h, 37C) in the presence of AAPH underwent a 75% decrease in its activity, a concomitant 50% loss of TAF, and a 6-fold rise in CO levels. Such a change in CO levels, however, could account at the most for the inactivation of 6% of the enzyme molecules. Further suggesting a dissociation between CO formation and inactivation, the enzyme's activity and the TAF remained totally unaltered upon exposure of the protein to Fe+2/A in spite of an almost 5-fold rise in CO. The effects induced by either AAPH or Fe+2/A were all inhibitable by antioxi dant addition. Nev

Emerging therapeutic approaches for Alzheimer's disease Enfoques terapéuticos emergentes para la enfermedad de Alzheimer

Alzheimer's disease is a therapeutic challenge of the first magnitude which has responded very unsatisfactorily to current treatments. Progress in the understanding of the processes associated with the pathogenesis and course of this disease suggest new therapeutic approaches, some of which are in clinical experimentation while others are still the subject of basic research. © 2006 Sociedad de Neurología, Psiquiatría y Neurocirugía

Alkaloids of the Cactaceae ? The Classics

Alkaloids of the Cactaceae have been studied for the last 120 years. The first half of that period provided the "classic" compounds, after which a large number of usually very similar analogs were isolated or determined with modern methods. Although some unusual synthetic approaches have been developed, their preparation is generally quite straightforward. Their biosynthesis has been studied but, particularly in the case of the isoquinoline compounds, important aspects have not been addressed. Due to its striking effects, the pharmacology of mescaline has been studied more intensely than that of the other phenethylamines present in cacti, followed only by hordenine. The many 1,2,3,4-tetrahydroisoquinoline alkaloids have attracted much less interest and have often been considered practically inactive. Nevertheless, some recorded activities of this group of compounds suggests a need for additional studies, especially in connection with their co-administration with mescaline, as in dried cacti and in beverages prepared from them

Simple and efficient synthesis of various dibenzofuran carbaldehydes

We herein report simple and efficient methods for the synthesis of various formyl derivatives of dibenzofuran. The aldehydes reported are prepared in at most three steps and in yields greater than 60% from commercially available dibenzofuran, with one exception where isomers must be separated. The protocols described involve either formylation of previously functionalized dibenzofuran derivatives or the initial introduction of the formyl group and subsequent further functionalization under standard reaction conditions as described. We have also reported an efficient and simple method for the synthesis of key methoxydibenzofurans in high yield (65% overall for two steps)CONICYT (Chile) through FONDECYT 315047

ADDITIONAL ALKALOIDS FROM LAURELIA PHILIPPIANA AND L. NOVAE-ZELANDIAE

Asimilobine. anonaine. noreorydine. nornantenine. (+)-reticuline and lhe new alkaloid. 4-hydroxyanonaine. were isolaled from Laur~litJpllilippialla bark. The biogenelically relaled obovanine. oxopulerine and (-)-romneine. not known as a natural produel. were oblained from lhe bark of L. lIol'a~-ulalldia~. The oeeurrenee of (R)-norlaudanosoline-derived alkaloids in L lIova~·ulallditJ~ is a distinctive feature of this tree. Neither L. not'at-ulalldiat nor L. pllilippiana aeeumulate dimeric benzylisoquinoline alkaloids lo any appreciable extenl in lhe lrunk bark. dilfering in this respeel from L. umptn·irtlls. the only other Laurtlia speeies.This work was supoported by DICYT and the Organization of American States

BISBENZYLISOQUINOLINE ALKALOIDS OF LA URELZA SEMPERVZRENS

The stem bark of Laurelia sempervirens R. et P. (Monimiaceae, subfamily Atherospermoideae) is a rich source of aporphinoids and has also been shown to contain a complex mixture of unidentified bisbenzylisoquinolines (1). The dimeric fraction has now been reexamined and its major components identified as obaberine, thalrugosine, and oxyacanthine. These alkaloids have not been reported previously as constituents of Monimiaceae, but they belong to the same stereochemical-biogenetic series as isotetrandrine, isolated from the leaves of L. sempewims (2) as well as from several other Atherospermoideae, and berbamine, daphnoline, daphnandrine, aromoline, homoaromoline, and more oxidized metabolites of Atherospenna moscbatum and several Daphnandra species (3).This work was supported by the Organization of American States and DICYT (USACH). We thank Prof. Maurice Shamma (The Pennsylvania State University) for the use of laboratory facilities during the initial fractionation

COMPONENTES ESTEROIDALES DE SOLANUM PINNATUM

Hojas y tallos de Solanum pinnatum Cav., cosechados cerca de Longotoma (Aconcagua), fueron procesados para estudiar su contenido de glicoalcaloides y sapogeninas neutras esteroidales. Se pudo aislar solasonina, solamargina, un tercer glicósido de solasodina que contiene glucosa y ramnosa, y diosgenina. El rendimiento de glicósidos crudos de solasodina fue de 30/0, lo que le otorga a esta planta interés como fuente industrialmente aprovechable de materias primas para la síntesis de hormonas esteroidales

SOLANACEAE SOLASODINE GLYCOSIDES AND DIOSGENIN FROM SOLANUM PINNATUM

A sample of a plant growing near Longotoma, Aconcagua, identified as Solanum pinnatum Cavo (Voucher specimen No. BClO deposited in the herbarium of the Museo Nacional de Historia Natural, Santiago), wás examined for glycoalkaloids and sapogenins. The crude basic glycoside mixture isolated from stems and lea ves afforded solasonine, solamargine, and a glucose- and rhamnose-containing glycoside of solasodine, probably identical with a previously described product obtained by partiaI hydrolysis of soIamargine.1 Hydrolysis of the remaining glycosides furnished two neutral compounds: diosgenin and (25R)-spirosta-3,5-diene.2FORGE, New York, for financial help

Dark Classics in Chemical Neuroscience: Mescaline

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote (Lophophora williamsii) and the South American wachuma (Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti "diabolic", leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or "mescal buttons" was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2A serotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure−activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogen