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Background The in vitro activity against Leishmania spp. of a novel group of compounds, phenalenone derivatives, is described in this study. Previous studies have shown that some phenalenones present leishmanicidal activity, and induce a decrease in the mitochondrial membrane potential in L. amazonensis parasites, so in order to elucidate the evidence of programmed cell death occurring inside the promastigote stage, different assays were performed in two different species of Leishmania. Methods We focused on the determination of the programmed cell death evidence by detecting the characteristic features of the apoptosis-like process, such as phosphatidylserine exposure, mitochondrial membrane potential, and chromatin condensation among others. Results The results showed that four molecules activated the apoptosis-like process in the parasite. All the signals observed were indicative of the death process that the parasites were undergoing. Conclusions The present results highlight the potential use of phenalenone derivatives against Leishmania species and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

Ultrafast photochromic molecules are being actively investigated to meet the demand for fast optical switching systems. Inspired on the irreversible cyclization of 9-phenylphenalenone plant metabolites to yield highly-coloured naphthoxanthenes for the purpose of defense against pathogens, aryl-substituted phenalenones have been developed that undergo a similar but reversible photochromic reaction. The lifetime of the naphthoxanthene photoisomer spans nine orders of magnitude, ranging from tens of picoseconds to tens of milliseconds depending on the electronic properties of the 9-aryl group.

The in vitro activity against Leishmania spp. of five novel designed compounds, phenalenone derivatives, is described in this study. Previous works have shown that some phenalenones present leishmanicidal activity, some of which could induce programmed cell death events in L. amazonensis parasites. In this research, we focused on the determination of the programmed cell death evidence by detecting the characteristic features of the apoptosis-like process, such as phosphatidylserine exposure and mitochondrial membrane potential, among others. The results showed that the new derivatives have comparable or better activity and selectivity than the commonly prescribed anti-leishmanial drug. This result was obtained by inducing stronger mitochondrial depolarization or more intense phosphatidylserine exposure than miltefosine, highlighting compound 8 with moreover 9-times better selectivity index. In addition, the new five molecules activated the apoptosis-like process in the parasite. All the signals observed were indicative of the death process that the parasites were undergoing.

Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100.

A collection of N-substituted quinolin-2(1H)-ones were screened against a panel of clinically relevant protozoa (Leishmania, Trypanosoma and Acanthamoeba). Three quinolin-2(1H)-one compounds were identified as selective anti-Acanthamoeba agents. Further assessment revealed that these compounds were active against both trophozoite and cyst forms of A. castellanii Neff, and caused protozoa death via apoptosis. The data presented herein identify N-acyl quinolin-2(1H)-ones as a promising new class of selective anti-Acanthamoeba agents.

Este trabalho acompanha as mudanças ocorridas no processo de planejamento, no tocante à prática efetiva, seu discurso legitimador e o padrão do Estado que o pratica, como observado na cidade de São Paulo, desde os finais dos anos 60 por um período de uma década, durante a qual esteve apoiado na ideologia da social democracia, até o início da década de 2000 a partir de quando se assentou firmemente sobre a ideologia neoliberal. Destaca-se que ambas as ideologias eram importadas dos países centrais, o que aponta para uma das peculiaridades fundamentais do processo de planejamento na sociedade de elite brasileira, a saber, o descolamento do discurso da prática do planejamento. Descreve o histórico da construção do processo de planejamento urbano e de seus instrumentos de regulação urbanística na cidade de São Paulo até a década de 70, concretizados no Plano Urbanístico Básico - PUB, no Plano Diretor de Desenvolvimento Integrado - PDDI e suas leis de zoneamento, sua desconstrução nas décadas seguintes e sua substituição por práticas e discurso inteiramente novos do Plano Diretor Estratégico - PDE, de 2002, dos Planos Regionais Estratégicos - PREs e a nova Lei de uso do solo de 2004. Nesta descrição são pontuadas a retórica e as práticas dos vários grupos que assumiram a administração municipal, além da academia e de outras organizações intervenientes na formação do espaço urbano. This dissertation outlines the changes in the planning process, with respect to actual practice, its rhetoric and the State itself which executes as observed in the city of São Paulo, since the late 60\'s for a period of a decade, during which it was supported by the ideology of social democracy, until the beginning of the 2000s from when he sat firmly on the neoliberal ideology. Calls attention to the fact that both ideologies were imported from developed countries, pointing to one of the fundamental peculiarities of the planning process of the Brazilian elite in society, namely the lack adherence of the discourse to planning practice. Further it describes the history of the construction of the urban planning process and its instruments of urban regulation in São Paulo until the 70\'s, embodied in the Basic Plan Urban - PUB, the Integrated Development Plan - PDDI and its zoning laws, its deconstruction in the following decades and replaced by the entirely new discourse and practices of the Strategic Master Plan - PDE, 2002, the Strategic Regional Plans - PREs and new land use law in 2004. In this description emphasis is given to both the rhetoric and practices of the various groups which were in change of the city government, and also university and other organizations involved in the formation of urban space.

The light-induced singlet oxygen production and antifungal activity of phenylphenalenone phytoalexins isolated from infected banana plants (Musa acuminata) are reported. Upon absorption of light energy all studied phenylphenalenones sensitise the production of singlet oxygen in polar and non-polar media. Antifungal activity of these compounds towards Fusarium oxysporum is enhanced in the presence of light. These results, together with the correlation of IC50 values under illumination with the quantum yield of singlet oxygen production and the enhancing effect of D2O on the antifungal activity, suggest the intermediacy of singlet oxygen produced by electronic excitation of the phenylphenalenone phytoalexins.

The singlet and triplet excited states of 9-phenylphenalenones 1 undergo β-phenyl quenching (BPQ) via addition of the carbonyl oxygen to the ortho position of the phenyl substituent. This reaction leads to the formation of naphthoxanthenes 4, which, in the absence of quenchers, undergo a very rapid electrocyclic ring opening reaction reverting to 1 within a few microseconds. Naphthoxanthene 4a contains a remarkably weak C–H bond, which enables efficient hydrogen transfer reactions to suitable acceptors, giving rise to the production of the naphthoxanthenyl radical or the naphthoxanthenium cation, depending on the solvent polarity. The study uncovers a number of new aspects of BPQ and suggests an excited state-mediated metabolic pathway in the biosynthesis of plant fluorones.

Multisubstituted piperidines containing a phenyl group at C-2 can be opened regio- and stereoselectively with cyanogen bromide. The ring-opened products contain useful cyanamide and benzylic bromide functional groups. This methodology is useful for the stereoselective synthesis of uniquely substituted alkylamine derivatives containing multiple chiral centers and various functionality.

A stereocontrolled first total synthesis of a diastereomer of the presumed mono-tetrahydrofuran type acetogenin annonacin A, starting with enantiomerically pure precursors, is described. The absolute stereochemistry of the C15−C20 segment corresponding to the tetrahydrofuran ring of the natural product was secured by X-ray crystal structure analysis of an advanced intermediate. The synthetic product (a mixture of epimers at C10) had spectroscopic data identical to that of the natural product, but a different optical rotation.

Several approaches for the stereocontrolled introduction of a 2-propyl group into (4S)-hydroxymethyl-1,4-butyrolactonevia enolate chemistry were investigated. A practical synthesis of the (2R)- and (2S)-isomers was developed.

Racemic cis-3-phenyl-acenaphthene-1,2-diol (1), a phytoanticipin, and the related phytoalexin, 4-phenyl-benzo[de]iso-chromene-1,3-dione (2) were prepared via a short sequence of reactions from a common intermediate. Dione2 was also used to prepare the imides 6-8 which are structurally related to a set of recently identified compounds possessing anti-tumor activities.

Four new phenalenone-type phytoalexins, named musanolones C-F, have been isolated from infected rhizomes of banana plants (Musa acuminata; AAA cultivar Grand Nain). These phytoalexins were biosynthesized de novo by the plants upon infection by Fusarium oxysporum f. sp. cubense race 4, Panama's disease causal agent. The structures of the new phytoalexins were elucidated using spectroscopic data and chemical correlations. Hydroxyanigorufone has been previously described as a constitutive natural product, from Anigozanthos rufus, but it was never described as a phytoalexin. The chemical shift for all of the hydrogen and carbon atoms in the musanolones C-F were unambiguously established by mono- and bi-dimensional, homo- and hetero-nuclear NMR experiments (1H NMR, 13C NMR, COSY, HMQC and HMBC). Preliminary in vitro assays of all the musanolones tested until now show a strong inhibitory activity on the growth of the germination tube of F. oxysporum f. sp. cubense race 4.

A set of derivatives encompassing structural modifications on the privileged phenalenone scaffold were assessed for their antiplasmodial activities against a strain of chloroquine sensitive Plasmodium falciparum F32. Two compounds exhibited considerable effects against the malaria parasite (IC50 ⩽ 1 μg/mL), one of which maintained the same level of activity in a chloroquine-resistant strain. This is the first record of antiplasmodial activity on this type of scaffold, providing a new structural motif as a new lead for antimalarial activity.

Two new 4-phenyl-phenalenone-type phytoalexins ( 2 , 3 ) have been isolated from rhizomes of Musa acuminata infected with the fungus Fusarium oxysporum . The structures of the new phytoalexins were elucidated on the basis of spectroscopic evidence, chemical correlation and synthesis from commercial phenalen-1-one. The chemical shift for all of the hydrogen and carbon atoms in the substances were unambiguously established by mono- and bidimensional, homo- and heteronuclear NMR experiments ( 1 H NMR, 13 C NMR, COSY, HMQC and HMBC). In preliminary “in vitro” assays, the new phytoalexins have shown inhibitory activity on the growth of the germinative tube of Fusarium oxysporum f. sp. cubense race 4 .

Three new natural diterpenes: 5,6-didehydro-7-hydroxy-taxodone (1), 17-hydroxycryptotanshinone (2) and salvicanaraldehyde (4) plus the known compounds: taxodione, taxodone, cryptotanshinone (3), 7α-hydroxyroyleanone, ferruginol, 6,7-didehydroferruginol (6), 6,7-didehydrosempervirol (7), demethylsalvicanol, salvicanaric acid (5) and the 11,12-dihydroxy-6,7-secoabieta-8,11,13-trien-6,7-dial-11,6-hemiacetals 9 and 10 were isolated from the roots of Salvia munzii. The structures of the new compounds were established from their spectroscopic data and by chemical correlations. The co-occurence of some of these compounds in the one species together with the results obtained of photochemical oxidation of 5,6-didehydro-7-hydroxytaxodone supports our earlier hypothesis of a biogenetic pathway to highly oxidized abietatriene diterpenes in which enzymatic dehydrogenation and singlet-state oxygen appear to play important roles.

Three new natural diterpenes: 5,6-didehydro-7-hydroxy-taxodone (1), 17-hydroxycryptotanshinone (2) and salvicanaraldehyde (4) plus the known compounds: taxodione, taxodone, cryptotanshinone (3), 7α-hydroxyroyleanone, ferruginol, 6,7-didehydroferruginol (6), 6,7-didehydrosempervirol (7), demethylsalvicanol, salvicanaric acid (5) and the 11,12-dihydroxy-6,7-secoabieta-8,11,13-trien-6,7-dial-11,6-hemiacetals 9 and 10 were isolated from the roots of Salvia munzii. The structures of the new compounds were established from their spectroscopic data and by chemical correlations. The co-occurence of some of these compounds in the one species together with the results obtained of photochemical oxidation of 5,6-didehydro-7-hydroxytaxodone supports our earlier hypothesis of a biogenetic pathway to highly oxidized abietatriene diterpenes in which enzymatic dehydrogenation and singlet-state oxygen appear to play important roles.

Two new 4-phenyl-phenalenone-type phytoalexins ( 2 , 3 ) have been isolated from rhizomes of Musa acuminata infected with the fungus Fusarium oxysporum . The structures of the new phytoalexins were elucidated on the basis of spectroscopic evidence, chemical correlation and synthesis from commercial phenalen-1-one. The chemical shift for all of the hydrogen and carbon atoms in the substances were unambiguously established by mono- and bidimensional, homo- and heteronuclear NMR experiments ( 1 H NMR, 13 C NMR, COSY, HMQC and HMBC). In preliminary “in vitro” assays, the new phytoalexins have shown inhibitory activity on the growth of the germinative tube of Fusarium oxysporum f. sp. cubense race 4 .

Several approaches for the stereocontrolled introduction of a 2-propyl group into (4S)-hydroxymethyl-1,4-butyrolactonevia enolate chemistry were investigated. A practical synthesis of the (2R)- and (2S)-isomers was developed.

The new natural diterpenes, 6,7-didehydroferruginol, 6,7-didehydrosempervirol, 16-hydroxy-6,7-didehydroferruginol, 11,12,16-trihydroxy-20(10 → 5)abeo-abieta-1(10),6,8,11,13-pentaene, the diterpene quinones, 16-hydroxyroyleanone and 6-deoxo-5,6-didehydrolanugon Q plus the known compounds ferruginol, miltiodiol, cryptotanshinone, lanugon Q and salvicanol were isolated from the roots of Salvia apiana . Their structures were established by spectrometry. The co-occurrence of so many abietane diterpenes with different degrees of oxidation and modified skeletons is in accordance with the biosynthetic route previously proposed for these compounds.

A set of derivatives encompassing structural modifications on the privileged phenalenone scaffold were assessed for their antiparasitic activities against the most clinically relevant forms of trypanosomiasis and leishmaniasis. Several compounds exhibited leishmanicidal effects at levels comparable or better than the reference drug pentamidine, while the parent phenalenone was shown to have a level of activity against Trypanosoma cruzi comparable to the marketed drug benznidazole.

Various multisubstituted piperidines containing a phenyl group at C-2 can be opened regio- and stereoselectively with cyanogen bromide. The ring-opened products contain useful cyanamide and benzylic bromide functional groups. The benzyl bromide can be cleanly reduced, or substituted with various nucleophiles via an S(N)2 process to add additional heteroatoms stereoselectively. This methodology is useful for the stereoselective synthesis of uniquely substituted alkylamine derivatives containing multiple chiral centers and various functionality. Diastereomerically pure amino alcohols containing three to five contiguous stereocenters were prepared using this strategy.

The aerial part of Salvia palaefolia yielded (−)-glechomafuran, 1β,10α;4α,5β-diepoxy-8β-hydroxyglechoman-8α,12-olide and the new eudesmanolides: 1α-acetoxy-8α-hydroxy-2-oxo-eudesman-3,7(11)-dien-8,12-olide and 1α,8α-dihydroxy-2-oxo-eudesman-3,7(11)-dien-8,12-olide. The structure of the former new compound was determined from its spectral data and chemical behaviour and its absolute configuration by CD experiments. The absolute configuration of 1β,10α;4α,5β-diepoxy-8β-hydroxyglechoman-8α,12-olide was established by X-ray diffraction analysis.

Three new ent-pimarane diterpenes were isolated from Palafoxia texana. Their structures were determined from the spectral evidence. The absolute configuration of 1 was established by means of circular dichroism analysis of a derivative.

Experiments were performed to elucidate the excited-state behavior of 9-phenylphenalenones, which are phototoxic plant secondary metabolites involved in mechanisms of light-mediated plant defense. Using a combination of time-resolved and steady-state UV/visible spectroscopies, time-resolved IR absorption spectroscopy, time-resolved singlet oxygen phosphorescence measurements and cyclic voltammetry, we provide evidence of an intramolecular charge-transfer process in the excited singlet and the triplet states of 9-phenylphenalenones that modulates the photosensitized production of singlet oxygen.

During a study on iodocyclocarbamation reactions of 2-styryl-4-piperidones, a novel ring contraction was observed. Iodocyclocarbamation of 2-styryl-4-piperidone 3 gave the bicyclic carbamate 4. Reduction of 4 under free-radical conditions effected a stereoselective ring contraction to provide oxazolidinone 6. A three-electron-three-center mechanism is proposed.

The aerial part of Salvia palaefolia has already yielded squalene, lupeol, taraxerol, taraxerone, β-amyrin, olean-12-en-3 one, oleanonic, oleanolic and ursolic acids, 5-hydroxy-7,6,8,4'-tetramethoxyflavone, caryophyllene, oxide, and an enantiomer of glechomafuran. More polar fractions of the same extract have now afforded a new β-agarofuran sesquiterpene, 1α,9β-dibenzoyloxy-2β,3β,4β-trihydroxydihydro-β-agarofuran {1}

Analysis of the aerial part of Ayeratum conyzoides afforded 11 chromenes, sitosterol, (+)-sesamin and caryophyllene oxide. One chromene is new and eight of the others were obtained for the first time from this species. The ‘C NMR spectral data for four of the chromenes have not been published before. INTRODUCIION Over the last two or three decades, great attention has been focused on the biological activity of natural com- pounds of plant origin for their potential as natural pesticides against phytophagous insects. In Colombia, plants have been used for centuries for their insecticidal. repellent or antifeedant properties in the protection of crops from insect attack [I]. Ageratum conyzoides, a widespread weed in Colombia and elsewhere, known to contain precocene I and precocene II [2,3], has been used both in folk medicine and as an insecticide. A study of the insecticidal activity of various fractions of an n-hexane extract of

Nine methoxyflavones were obtained from aerial parts of Ageratum conyzoides , two of which are new: 5,6,8,3′,4′,5′-hexamethoxyflavone and 8-hydroxy-5,6,7,3′,4′,5′-hexamethoxyflavone.

Five minor eudesmane constituents of Salvia palaefolia were isolated from the same extract which had earlier yielded the two fully characterized eudesmanolides. The five new natural compounds were identified by spectral studies and comparison with known substances.

Three new intermediates (1 – 3) in de novo biosynthetic pathway to phenyl-phenalenone-type phytoalexins have been isolated from rhizomes of Musa acuminata infected with the fungus Fusarium oxysporum. The structures of the new pre-phytoalexins were elucidated on the basis of spectroscopic evidences, chemical correlation and acid catalyzed biomimetic cyclization of 1 to emenolone (4), isolated from the same source and whose previously reported structure has been unambiguously corrected by X-ray diffraction analysis. The chemical shift for all of the hydrogen and carbon atoms in the substances were unambiguously established by mono- and bidimensional, homo- and heteronuclear NMR experiments (1H NMR, 13C NMR, COSY, ROESY, HMQC and HMBC).

The new diterpenequinone columbaridione, together with the known compounds 7-methoxyrosmanol, 7-ethoxyrosmanol, 11-acetoxy carnosic acid, 20-deoxocarnosol and miltidiol were isolated from the aerial part of Salvia columbariae. The structure of the new diterpenequinone was established from spectral data and chemical correlations.

The new diterpenes 11,12-di-O-methylrosmanol and 11,12-di-O-methylcarnosol, together with the known compounds carnosic acid, carnosol, rosmanol, epirosmanol, isorosmanol, salvicanol and rosmadial were isolated from the aerial part of Salvia columbariae. The structures of the new diterpenes were established from their spectral data and by chemical correlations. The co-occurence of all these compounds in a single species provides further support of our previously postulated biogenetic pathway to highly oxidized abietatriene compounds involving enzymatic dehydrogenation processes and the participation of singlet oxygen.

A new aromatic diterpene has been obtained from the aerial parts of Salvia munzii and its structure identified on the basis of spectral data as 16

The aerial part of Salvia palaefolia yielded squalene, lupeol, taraxerol, taraxerone, β-amyrin, olean 12-en-3-one, oleanonic acid, oleanolic acid, and ursolic acid, together with 5-hydroxy-7,6,8,4'-tetramethoxyflavone, caryophyllene oxide, and an enantiomer of glechomafuran. The compounds were identified by spectroscopy, X-ray analysis