Jacqueline A. Takahashi

Biological screening of Annonaceous Brazilian Medicinal Plants using Artemia salina (Brine Shrimp Test)

Eighteen different extracts from five Annona species collected in Minas Gerais state, Brazil, were submitted to the brine shrimp lethality test in order to detect potential sources of novel cytotoxic, antitumor, pesticidal and anti-Trypanosoma cruzi compounds. All of the Annonaceous species tested showed good larvicidal activity as compared to a reference compounds and literature data.

N(4)-tolyl-2-benzoylpyridine thiosemicarbazones and their copper(II) complexes with significant antifungal activity: crystal structure of N(4)-para-tolyl-2-benzoylpyridine thiosemicarbazone

) para os complexos. Nossos resultados sugerem que a coordenacao ao cobre constitui estrategia interessante de reducao da dose necessaria a atividade. Three new copper complexes of general formula [Cu(HL)Cl 2 ] have been obtained with N(4)-ortho (H2Bz4oT, HL1), N(4)-meta (H2Bz4mT, HL2) and N(4)-para-tolyl-2-benzoylpyridine thiosemicarbazone (H2Bz4pT, HL3), in which the thiosemicarbazone attaches to the metal through the N py -N-S chelating system. H2Bz4pT (HL3) crystallizes in the P1 – space group, with a = 9.509(3) A, b = 9.807(4) A, c = 11.564(4) A; α = 100.76(2)°, β = 105.99(2)°, γ = 114.59(2)°. The thiosemicarbazones and their copper(II) complexes exhibit high antifungal activities against Candida albicans with low values of minimum inhibitory concentration (MIC), in the 8-0.3 μg mL -1 (23 – 0.7 μmol L -1 ) range for the free bases and in the 1-0.1 μg mL -1 (2 – 0.3 μmol L -1 ) range for the complexes. Our results suggest that coordination to copper(II) could be an interesting strategy for dose reduction.

Antibacterial activity of eight Brazilian annonaceae plants

Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X. amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A. cherimolia. Amongst the investigated extracts, six showed antibacterial activity against at least one of the tested organisms at the concentration of 100 µg/mL. The most active extracts were those prepared from X. frutescens, X. amazonica, and A. ambotay. A phytochemical screening showed the presence of anonaceus acetogenins in some active extracts. Eleven diterpenoids were also tested for comparison purposes. Six were natural products, previously isolated from Xylopia sp. (kaurenoic, frutoic, xylopic, 15β-hydroxy-kaurenoic and trachylobanic acids plus kaurenol) and five were derivatives of such compounds, obtained by esterification or reduction reactions. Trachylobanic acid showed antibacterial activity against B. subtilis and S. aureus.

Design, structural and spectroscopic elucidation, and the in vitro biological activities of new diorganotin dithiocarbamates.

The reaction of 2,2-dimethoxy-N-methylethyllamine or 2-methyl-1,3-dioxolane with CS(2) in alkaline media produced two novel dithiocarbamate salts. Subsequent reactions with organotin halides yielded six new complexes: [SnMe(2){S(2)CNR(R(1))(2)}(2)] (1), [Sn(n-Bu)(2){S(2)CNR(R(1))(2)}(2)] (2), [SnPh(2){S(2)CNR(R(1))(2)}(2)] (3), [SnMe(2){S(2)CNR(R(2))(2)}(2)] (4), [Sn(n-Bu)(2){S(2)CNR(R(2))(2)}(2)] (5), [SnPh(2){S(2)CNR(R(2))(2)}(2)] (6), where R = methyl, R(1) = CH(2)CH(OMe)(2), and R(2) = 2-methyl-1,3-dioxolane. All compounds were identified in terms of infrared, (1)H and (13)C NMR, and the complexes were also characterized using (119)Sn NMR, (119)Sn Mössbauer and X-ray crystallography. The biological activity of all derivatives has been screened in terms of IC(90) and IC(50) against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum, Curvularia senegalensis, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus sanguinis, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and Pseudomonas aeruginosa and the results correlated well with a performed study of structure-activity relationship (SAR). Complexes (3), (5) and (6) displayed the best IC(90) and IC(50) in the presence of the fungi, greater than that of miconazole, used as control drug.

Novel antimicrobial secondary metabolites from a Penicillium sp. isolated from Brazilian cerrado soil

Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.12 No.4, Issue of October 15, 2009

Antimicrobial properties of sclerotiorin, isocHromophilone VI and pencolide, metabolites from a Brazilian cerrado isolate of Penicillium sclerotiorum van Beyma

As a part of a research program that aims to identify antibacterial and antifungal substances from fungus specimen of Brazilians cerrado soil samples, Penicillium sclerotiorum was identified as a source of secondary metabolites possessing antibiotic activities. This microorganism was cultured in a liquid medium rich in glucose for fifteen days. The resulting ethyl acetate extract was chemically fractionated leading to the isolation of three metabolites pencolide, sclerotiorin and isochromophilone VI. The antimicrobial disc assay activity of these substances towards Candida albicans, Streptomyces pyogenes, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli was performed. Minimum inhibitory concentration (MIC) of the compounds was determined. All compounds showed distinguished antimicrobial activities.

New Triterpenes from Maytenus robusta: Structural Elucidation Based on NMR Experimental Data and Theoretical Calculations

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

Frutoic acid, a dimeric kaurane diterpene from Xylopia frutescens

Sitosterol and six diterpenes were isolated from green fruit, stem bark and leaves of Xylopia frutescens and characterized as ent-15α-acetoxy-kaur-16-en-19-oic acid (xylopic acid), ent-kaur-16-en-19-oic acid (kaurenoic acid), ent-16β-hydroxy-kaurane, ent-kaur-16-en-19-ol, ent-16β-hydroxy-kauran-19-oic acid and ent-16β,17-dihydroxy-kauran-19-oic acid. Acutifloric acid, a diterpenic dimer, and its 7β-hydroxy-derivative, a novel compound named frutoic acid, were also isolated.

Novel Derivatives of Kaurenoic Acid

Kaurenoic acid, a kauranic diterpenoid, presents in vitro activity against trypomastigote forms of Trypanosoma cruzi, showing, however, lytic activity on blood erythrocytes, as a side effect. The syntheses of twelve new derivatives of kaurenoic acid, four amides, four amines (and three hydroclorides) and four oximes, was carried out aiming at the improvement of the therapeutic activity and without the side effect. Among the derivatives prepared, one compound showed enhanced trypanocidal activity in vitro towards Trypanosoma cruzi trypomastigote erythrocytic forms, when compared to kaurenoic acid, but continued to show discrete lytic activity on erythrocytes; another compound showed a level of activity similar to that of kaurenoic acid, but without lysis.

Two C10 lactones from Cephalosporium aphidicola

Abstract Cephalosporolide G, diplodialide B and Z-3-methylpent-2-en-1,5-dioic acid have been obtained from the fungus, Cephalosporium aphidicola .