Triterpenes from Minquartia guianensis (Olacaceae) and in vitro antimalarial activity

Minquartia guianensis, popularly known as acariquara, was phytochemically investigated. The following triterpenes were isolated from the dichloromethane extract of leaves: lupen-3-one (1), taraxer-3-one (2) and oleanolic acid (3). The dichloromethane extract of branches yielded the triterpene 3β-methoxy-lup-20(29)-ene (4). The chemical structures were characterized by NMR data. Plant extracts, substance 3, squalene (5) and taraxerol (6), (5 and 6 previously isolated), were evaluated by in vitro assay against chloroquine resistant Plasmodium falciparum. The dichloromethane extract of leaves and the three triterpenes assayed have shown partial activity. Thus, these results demonstrated that new potential antimalarial natural products can be found even in partially active extracts.

Chemical constituents from red algae Bostrychia radicans (Rhodomelaceae): new amides and phenolic compounds

This study describes the isolation and structural determination of two amides, isolated for the first time: N,4-dihydroxy-N-(2'-hydroxyethyl)-benzamide (0.019%) and N,4-dihydroxy-N-(2'-hydroxyethyl)-benzeneacetamide (0.023%). These amides, produced by the red macroalgae Bostrychia radicans, had their structures assigned by NMR spectral data and MS analyses. In addition, this chemical study led to the isolation of cholesterol, heptadecane, squalene, trans-phytol, neophytadiene, tetradecanoic and hexadecanoic acids, methyl hexadecanoate and methyl 9-octadecenoate, 4-(methoxymethyl)-phenol, 4-hydroxybenzaldehyde, methyl 4-hydroxybenzeneacetate, methyl 2-hydroxy-3-(4-hydroxyphenyl)-propanoate, hydroquinone, methyl 4-hydroxymandelate, methyl 4-hydroxybenzoate, 4-hydroxybenzeneacetic acid and (4-hydroxyphenyl)-oxo-acetaldehyde. This is the first report concerning these compounds in B. radicans, contributing by illustrating the chemical diversity within the Rhodomelaceae family.

Tropical biodiversity: has it been a potential source of secondary metabolites useful for medicinal chemistry?

The use of natural products has definitely been the most successful strategy in the discovery of novel medicines. Secondary metabolites from terrestrial and marine organisms have found considerable use in the treatment of numerous diseases and have been considered lead molecules both in their natural form and as templates for medicinal chemistry. This paper seeks to show the great value of secondary metabolites and emphasize the rich chemical diversity of Brazilian biodiversity. This natural chemical library remains understudied, but can be a useful source of new secondary metabolites with potential application as templates for drug discovery.

Otto R. Gottlieb e as conexões com o Brasil de Ernest Wenkert

Prof. Ernest Wenkert's connections with Brazil on this side of the Atlantic Ocean involved two important links: Profs. Jayr de Paiva Campello and Otto R. Gottlieb. The former, along with Prof. Giuseppe Cilento, was one of those responsible for setting up the Institute of Chemistry of UNICAMP, while Otto Gottlieb was the great pioneer of Natural Products Chemistry in Brazil. The bridge between these two professors and Wenkert paved the way for several Brazilian chemists to visit the USA, and was also important for bringing some PhDs to Brazil.

Explorando produtos naturais microbianos nas fronteiras da Química e da Biologia

The chemistry of natural products has been remarkably growing in the past few decades in Brazil. Aspects related to the isolation and identification of new natural products, as well as their biological activities, have been achieved in different laboratories working on this subject in the country. More recently, the introduction of new molecular biology tools has strongly influenced the research on natural products, mainly those produced by microorganisms, creating new possibilities to assess the chemical diversity of secondary metabolites. This paper describes some ideas on how the research on natural products can have a considerable input from molecular biology in the generation of chemical diversity. We also explore the role of microbial natural products in mediating interspecific interactions and their relevance to ecological studies. Examples of the generation of chemical diversity are highlighted by using genome mining, mutasynthesis, combinatorial biosynthesis, metagenomics, and synthetic biology, while some aspects of microbial ecology are also discussed. The idea to bring up this topic is linked to the remarkable development of molecular biology techniques to generate useful chemicals from different organisms. Here, we focus mainly on microorganisms, even though similar approaches have also been applied to the study of plants and other organisms. Investigations in the frontier of chemistry and biology require interactions between different areas, characterizing the interdisciplinarity of this research field. The necessity of a real integration of chemistry and biology is pivotal to finding correct answers to a number of biological phenomena. The use of molecular biology tools to generate chemical diversity and control biosynthetic pathways is largely explored in the production of important biologically active compounds. Finally, we briefly comment on the Brazilian organization of research in this area, the necessity of new strategies for the graduation programs, and the establishment of networks as a way of organization to overcome some of the problems faced in the area of natural products.

Química de productos naturales aplicada a la acuicultura: una revisión interdisciplinar

This review sought to highlight the importance of natural products versus synthetic products, as bioactive molecules, towards the development of better management practices in aquaculture. The nature, structure, activity, and applications of these naturally-occurring high value-added compounds are described, as well as the methodology used for their study. Examples include the well-known rotenone, eugenol, forskolin, isatin, malyngamide, chlorodesmine, pachydictyol, fimbrolide, and other potentially active molecules in aquaculture.

Flavonoides de Lonchocarpus araripensis (Leguminoseae) - isolamento, atribuição inequívoca dos sinais de RMN ¹H e 13C e análise conformacional

In a continuing investigation for potentially bioactive natural products, flavonoids were isolated from Lonchocarpus araripensis (Leguminoseae) and identified as 3-methoxy-6-O-prenyl-6'',6''-dimethylchromene-[7,8,2'',3'']-flavone (1), 3,6-dimethoxy-6'',6''-dimethylchromene-[7,8,2'',3'']-flavone (2) and 3,5,8-trimethoxy-[6,7,2",3"]-furanoflavone (3). This is the first time compound 3 has been described. Compound 2 has been previously isolated from roots while this is the first time 1 is reported in this species. Complete NMR assignments are given for1 ,2 and 3 together with the determination of conformation for 1.

Sínteses totais das enoquipodinas

Enokipodins comprises a family of sesquiterpenes isolated from the mushroom Flammulina velutipes. These substances are attractive synthetic targets due to either their biological potential or structural characteristics. Since their isolation, about a decade ago, a considerable number of successful total syntheses have been published. Both via a racemic or enantioselective approach, these studies describe original and creative synthetic routes, particularly concerning the methodology used for constructing the benzylic quaternary center of these natural products. In this brief review, we discuss the reported total synthesis of enokipodins, focusing on the strategy adopted for the quaternary stereogenic center.

CHEMICAL STUDY OF Hortia superba (Rutaceae) AND INVESTIGATION OF THE ANTIMYCOBACTERIAL ACTIVITY OF CRUDE EXTRACTS AND CONSTITUENTS ISOLATED FROM Hortia SPECIES

In this paper, the chemical study of Hortia superba and antimycobacterial potential of Hortia species were investigated. Crude extracts and limonoids, alkaloids, dihydrocinnamic acid derivatives and coumarins isolated from Hortia superba, Hortia oreadica and Hortia brasiliana were evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and Mycobacterium avium. The results obtained demonstrated an inhibitory effect of the dichloromethane extract of leaves of H. oreadica (MIC 31.25 µg mL-1), indolequinazoline (15.62 µg mL-1) and furoquinoline (31.25 µg mL-1) alkaloids, and dihydrocinnamic acid derivatives (62.50 µg mL-1), on the growth of M. tuberculosis. These results are promising in relation to the search for biologically active natural products and could be useful in the development of effective new drugs against mycobacteria.

TRIAGEM METABÓLICA POR PKS E NRPS EM ACTINOBACTÉRIAS ENDOFÍTICAS DE Citrus reticulata

Polyketides and non-ribosomal peptides are natural products widely found in bacteria, fungi and plants. The biological activities associated with these metabolites have attracted special attention in biopharmaceutical studies. Polyketide synthases act similarly to fatty acids synthetases and the whole multi-enzymatic set coordinating precursor and extending unit selection and reduction levels during chain growth. Acting in a similarly orchestrated model, non-ribosomal peptide synthetases biosynthesize NRPs. PKSs-I and NRPSs enzymatic modules and domains are collinearly organized with the parent gene sequence. This arrangement allows the use of degenerated PCR primers to amplify targeted regions in the genes corresponding to specific enzymatic domains such as ketosynthases and acyltransferases in PKSs and adenilation domains in NRPSs. Careful analysis of these short regions allows the classifying of a set of organisms according to their potential to biosynthesize PKs and NRPs. In this work, the biosynthetic potential of a set of 13 endophytic actinobacteria from Citrus reticulata for producing PKs and NRP metabolites was evaluated. The biosynthetic profile was compared to antimicrobial activity. Based on the inhibition promoted, 4 strains were considered for cluster analysis. A PKS/NRPS phylogeny was generated in order to classify some of the representative sequences throughout comparison with homologous genes. Using this approach, a molecular fingerprint was generated to help guide future studies on the most promising strains.

SÍNTESE DE ÁCIDOS CUMARINO-3-CARBOXÍLICOS E SUA APLICAÇÃO NA SÍNTESE TOTAL DA AIAPINA, CUMARINA E UMBELIFERONA

The synthesis of 3-coumarin-carboxylic acids and their application to the total synthesis of the natural products ayapin, coumarin, and umbeliferone in undergraduate organic chemistry experiments is described herein. The synthetic approach consists of a one-pot cyclization between salyciladehydes and Meldrum's acid in water to produce the above mentioned acids, followed by decarboxylation under basic or radical conditions.

ATRIBUIÇÃO DA ESTEREOQUÍMICA DA α-SANTONINA ATRAVÉS DAS MEDIDAS DO ACOPLAMENTO DIPOLAR RESIDUAL

The measurement of nuclear magnetic resonance parameters in an anisotropic media, such as residual dipolar coupling (RDC), has proven to be an excellent methodology for the refinement of chemical structures, being used as a complementary tool in the determination of the relative configuration, conformation, and constitution of organic compounds. In this study, we applied this methodology to determine the relative configuration of α-santonin, a natural product with four stereocenters, while assigning its prochiral methylene protons using only the RDCs obtained in a polyacrylonitrile polymer gel swollen in DMSO-d6.

ALCALOIDES ACRIDÔNICOS INIBEM CATEPSINA L E V

Cathepsins represent a class of enzymes that has the primary function of randomly degrading proteins in the lysosomes, although are also involved in different pathologies. The aim of this paper was to evaluate the capacity of acridone alkaloids isolated from Swinglea glutinosa (Rutaceae) to inhibit cathepsin L in vitro . The IC50 values found were in the 0.8-57 µM range and the most promising compounds were alkaloids 1 and 2, with IC50 of 0.9 and 0.8 µM, respectively. Enzyme kinetics revealed that they are reversible competitive inhibitors with respect to the substrate Z-FR-MCA. This small series of acridone alkaloids showed low selectivity for both cathepsins, but represent promising lead candidates for the further development of competitive cathepsin L and V inhibitors.

Family-based dietary intervention in the STRIP study – influences on diet and diet-related attitudes

The focus of this dissertation was to investigate the effects of family-based dietary intervention during childhood and adolescence. The participants comprised of children and parents who participated in a longitudinal, randomised atherosclerosis prevention trial (STRIP study). The intervention families (n=540) took part in a dietary intervention since the child’s age of 8- months. The control group (n=522) did not receive any tailored dietary intervention. The main focus of the intervention was to improve the quality of dietary fat. The diet of children and parents was evaluated by daily food records and dietrelated attitudes by a questionnaire. The dietary intervention influenced, favourably, the dietary fat quality in children and parents. Fat quality improved mainly by the decrease of saturated fat intake. Some minor effects of the intervention were also observed in children’s fruit and vegetable (F&V) consumption although the F&V consumption was very low. The intervention increased parental interest in healthy eating, but there was no difference in interest in natural products or in attitudes towards hedonic eating attitudes between the intervention and control parents. Parents’ interest in healthy eating associated with parents’ and children’s high fruit and vegetable consumption but not with their fat quality ratio. On the other hand, dietary fat quality improved at every level of interest in healthy eating. It seems that the main target of the intervention, the dietary fat quality of the children, was promoted effectively. In the future, more emphasis should be given on increasing unsaturated fat intake and on elevating F&V consumption in children. Children’s diet, especially F&V consumption, associated with diet-related attitudes of the parents. Therefore, co-operation with parents and family-based premises for working should be capitalized upon when promoting healthy eating in children and adolescents.

Computational chemistry studies of wood-derived lignans

This thesis is based on computational chemistry studies on lignans, focusing on the naturally occurring lignan hydroxymatairesinol (HMR) (Papers I II) and on TADDOL-like conidendrin-based chiral 1,4-diol ligands (LIGNOLs) (Papers III V). A complete quantum chemical conformational analysis on HMR was previously conducted by Dr. Antti Taskinen. In the works reported in this thesis, HMR was further studied by classical molecular dynamics (MD) simulations in aqueous solution including torsional angle analysis, quantum chemical solvation e ect study by the COnductorlike Screening MOdel (COSMO), and hydrogen bond analysis (Paper I), as well as from a catalytic point of view including protonation and deprotonation studies at di erent levels of theory (Paper II). The computational LIGNOL studies in this thesis constitute a multi-level deterministic structural optimization of the following molecules: 1,1-diphenyl (2Ph), two diastereomers of 1,1,4-triphenyl (3PhR, 3PhS), 1,1,4,4-tetraphenyl (4Ph) and 1,1,4,4-tetramethyl (4Met) 1,4-diol (Paper IV) and a conformational solvation study applying MD and COSMO (Paper V). Furthermore, a computational study on hemiketals in connection with problems in the experimental work by Docent Patrik Eklund's group synthesizing the LIGNOLs based on natural products starting from HMR, is shortly described (Paper III).