Anti-Inflammatory and Antinociceptive Properties of Kielmeyerone A, a Chromenone Isolated from the Roots of Kielmeyera reticulata.

Four new chromenones, kielmeyerones A-D (1-4), were obtained from the roots of Kielmeyera reticulata. Their structures were elucidated based on spectroscopic data (NMR and HRESIMS) interpretation. The pharmacological activity of kielmeyerone A (1), the major compound, was evaluated using in vitro and in vivo inflammation and pain models. During in vitro screening, 1, at noncytotoxic concentrations (0.097-1.56 µM), inhibited NO production by J774 macrophages stimulated with LPS and IFN-γ. In the complete Freund's adjuvant-induced inflammation model in mice, 1 (12.5-50 mg/kg) inhibited paw edema, demonstrating an anti-inflammatory effect. Additionally, 1 (12.5-50 mg/kg) induced a dose-dependent antinociceptive effect in the late phase of the formalin test, a profile similar to those of nonsteroidal anti-inflammatory drugs. Mice treated with 1 (100 mg/kg) did not show motor performance alterations using a rota-rod test. Thus, the present study has characterized new chromenones from Kielmeyera reticulata and has provided evidence of the anti-inflammatory and antinociceptive properties of one of these, kielmeyerone A (1).

Prenylated 4-phenylcoumarins and 4-alkylcoumarins from Kielmeyera argentea and their cytotoxic activity.

Two new prenylated 4-phenylcoumarins, named kielcoumarin A (1) and kielcoumarin B (2) together with three known compounds, mammea B/BA (3), mammea B/BA cyclo F (4) and ferruol A (5), were obtained from stems and roots of Kielmeyera argentea (Calophyllaceae). Their structures were elucidated based on spectroscopic data. Cytotoxic activity of the 4-alkylcoumarins 3-5 was evaluated in vitro against human U251 glioblastoma cell line. Compound 3 showed significative activity with EC50 value of 6.6 µM while compounds 4 and 5 showed respective EC50 values of 52.0 and 37.0 µM.

Novel polyprenylated benzophenone derivatives from Clusia burle-marxii.

Three new caged polyprenylated benzophenone derivatives named burlemarxiones D-F (1-3) were isolated from the hexane extract of Clusia burle-marxii trunks. Burlemarxione D (1) contains the tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton also observed for burlemarxione A, its probable immediate precursor. However, two additional rings are formed to produce an unprecedented complex-caged core skeleton. These additional rings could be formed by a radical cyclization reaction of one prenyl group at C-5 with C-1 and C-33, followed by oxidative dehydrogenation (rearomatization) or by an intramolecular [4 + 2] radical cycloaddition (Diels-Alder reaction), followed by an enolization reaction (rearomatization). Burlemarxiones E and F were isolated after methylation with diazomethane that was necessary to avoid the interconversion of the pair of ß-diketones in tautomeric equilibrium. The proposed biosynthetic pathway for burlemarxiones D-F involves the condensation of either lavandulyl pyrophosphate or 2-(1-methylvinyl)-hexa-5-enyl pyrophosphate with the acylphloroglucinol derivative 6-benzoyl-5-hydroxy-5-cyclohexen-1,3-dione, followed by consecutive prenylation reactions. Therefore, Clusia burle-marxii reinforces the claim that the genus Clusia is an important source of sophisticated caged polyprenylated benzophenone derivatives.

Polyprenylated benzophenone derivatives with a novel tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton from Clusia burle-marxii exhibited cytotoxicity against GL-15 glioblastoma-derived human cell line.

Three new polyprenylated benzophenone derivatives (1-3) were identified in the hexane extract of Clusia burle-marxii trunks, through the isolation and structural elucidation of their methyl derivatives, along with two known polyprenylated benzophenone derivatives sampsonine N (4) and obdeltifolione C (5). Burlemarxiones A (1) and B (2) show an unprecedent tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton. These compounds are a pair of ß-diketones in tautomeric equilibrium, whereas isonemorosonol (3) is the respective ß-diketone pair in tautomeric equilibrium with nemorosonol. Burlemarxione A methyl derivative (1a) and sampsonine N exhibited strong in vitro cytotoxic activity against GL-15 glioblastoma-derived human cell line.

Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi cells.

Chagas disease causes considerable morbimortality in the Americas, with circa 7 to 8 million infected people, causing at least 12,000 annual deaths and 100 million people at risk. Its chemotherapy is poorly selective and effective, associated to severe side effects and unresponsive cases. Thus, R&D on therapeutic alternatives is undoubtedly required. The Brazilian poorly studied biodiversity offers uncountable bioagents, which may be exploited for chemotherapy. The triterpene arjunolic acid (AA), reduced the Trypanosoma cruzi epimastigote in vitro proliferation with an apparent IC50 of 171 µM. Electron microscopy analysis revealed remarkable effects on the parasite surface and architecture. AA-treated parasites displayed minutely corrugated plasma membranes devoid of subpellicular microtubules as well as biogenesis of multiple basal bodies. As the AA effects appeared mainly restricted or originated at the parasite peripheral cytoplasm, including the cytoskeleton membrane linkage, we inferred that the compound targeted primarily the lipid bilayer; therefore, we performed synthetic modification to increase the molecule lipophilicity and thus membrane permeability. The methyl ester (MeAA) and tri-acetylated derivatives (3AcAA) had potentiated trypanocidal activity, producing IC50 values of 21.9 and 15.8 µM, respectively. Both derivatives were able to produce remarkable ultrastructural alterations in the parasites, including inner compartments such as Golgi apparatus and the endocytic/autophagic pathway. Parasites cultured with both derivatives displayed numerous and large autophagic vacuoles, altered flagellar length and cell body connection. These data indicate that synthetically-modified natural products comprise valuable tools in antiparasitic chemotherapy and that electron microscopy may be useful not only in determining the mechanisms of action but also in directing such modifications for rational drug design.

A new biphenyl and antimicrobial activity of extracts and compounds from Clusia burlemarxii.

Phytochemical investigation on Clusia burlemarxii (Clusiaceae) led to isolation and identification of nine compounds. Were isolated from leaves 3-O-α-L- rhamnopyranosylquercetin, 3-O-α-L-rhamnopyranosylkaempferol, 4-hydroxy-5,5-dimethyldihydrofuran-2-one, 2Z-δ-tocotrienoloic acid and friedelin and were isolated from trunk betulinic acid, protocatechuic acid, lyoniresinol, and a new biphenyl 2,2-dimethyl-3,5-dihydroxy-7-(4-hydroxyphenyl)chromane. The structures were determined by ¹H, ¹³C-NMR, DEPT, HMBC, HMQC, HRESIMS. The Minimal Inhibitory Concentration against Streptococcus mutans, Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli, Salmonella choleraesuis, Pseudomonas aeruginosa, Aspergillus niger and Cladosporium cladosporioides was also determined. Extracts and compounds showed significant activity against tested Gram-positive bacteria, none activity against tested Gram-negative bacteria and fungi.

New (9betaH)-lanostanes and lanostanes from Mikania aff. jeffreyi (Asteraceae).

Four new (9betaH)-lanostanes, i.e., (9betaH)-3beta-acetoxylanosta-7,24-diene, (9betaH)-3-oxolanosta-7,24-diene, (9betaH,24R)-3beta-acetoxy-24-hydroxylanosta-7,25-diene, and (9betaH,24S)-3beta-acetoxy-24-hydroxylanosta-7,25-diene, two new lanostanes, i.e., (24R)-3beta-acetoxy-24-hydroxylanosta-8,25-diene and (24S)-3beta-acetoxy-24-hydroxylanosta-8,25-diene, and two known lanostanes, i.e., 3beta-acetoxylanosta-8,24-diene and 3-oxolanosta-8,24-diene, were obtained from a new Mikania species (Asteraceae) besides pentacyclic triterpenes, steroids, and diterpenes. The structures of the compounds were determined by spectroscopic methods. This is the second study about acetyl-lanosterols from higher plants. Moreover, (9betaH)-lanostanes are very rare metabolites from dicotyledone angiosperms. The occurrence of these terpenes together in the same plant makes the species a good source for lanostane- and (9betaH)-lanostane-biosynthesis studies.

Xantonas, triterpenos e atividade antibacteriana do extrato em diclorometano de Kielmeyera cuspidata Saddi, Clusiaceae / Xanthones, triterpenes and antibacterial activity of dichloromethane extract of Kielmeyera cuspidata Saddi, Clusiaceae

Do extrato em diclorometano do tronco de Kielmeyera cuspidata Saddi, Clusiaceae, foram isoladas cinco xantonas, 1,6-diidroxi-3,5-dimetoxixantona, 2-hidroxi-1-metoxixantona, 2,3-metilenodioxixantona, 4-hidroxi-2,3-metilenodioxixantona e 3-hidroxi-2,4-dimetoxixantona e dois triterpenos, α-amirina e β-amirina. O extrato exibiu toxicidade para Artemia salina e atividade antibacteriana para Micrococcus luteus, Bacillus subitilis, Staphylococcus aureus e Streptococcus mutans, não sendo ativo para Escherichia coli, Pseudomonas aeruginosa e Salmonela choleraesuis.

From the dichloromethane extract of trunk of Kielmeyera cuspidata five xanthones were isolated, 1,6-dihydroxy-3,5-dimethoxyxanthone, 2-hydroxy-1-methoxyxanthone, 2,3-methylenedioxyxanthone, 4-hydroxy-2,3-methylenedioxyxanthone and 3-hydroxy-2,4-dimethoxyxanthone and two triterpenes α-amirin and β-amirin. The extract displayed toxicity against Artemia salina and exhibited antibacterial activity against Micrococcus luteus, Bacillus subitilis, Staphylococcus aureus and Streptococcus mutans and it was not active against Escherichia coli, Pseudomonas aeruginosa and Salmonela choleraesuis.

Preliminary studies on the volatile constitution of Mikania species / Estudos preliminares dos constituintes voláteis de espécies de Mikania

Volatile oils obtained from the aerial parts of three Mikania species plants were analyzed by GC-MS and NMR. Forty-six terpenes among monoterpenes, sesquiterpenes and diterpenes were identified by this methodology. The analysis classified Mikania hookriana as diterpene producer as the majority Mikania species occurring in Brazil.

Óleos voláteis obtidos das partes aéreas de plantas de três espécies de Mikania foram analisados por CG-EM e RMN. Quarenta e seis terpenos, entre monoterpenos, sesquiterpenos e diterpenos, foram identificados. A análise classificou Mikania hookeriana como produtora de diterpenos, de acordo com a maioria das espécies de Mikania que ocorrem no Brasil.