Emerson Peter da Silva Falcão

Usnic acid potassium salt: an alternative for the control of Biomphalaria glabrata (Say, 1818).

In Brazil, the snail Biomphalaria glabrata is the most important vector of schistosomiasis due to its wide geographical distribution, high infection rate and efficient disease transmission. Among the methods of schistosomiasis control, the World Health Organization recommends the use of synthetic molluscicides, such as niclosamide. However, different substances of natural origin have been tested as alternatives for the control or eradication of mollusks. The literature describes the antitumor, antimicrobial and antiviral properties of usnic acid as well as other important activities of common interest between medicine and the environment. However, usnic acid has a low degree of water solubility, which can be a limiting factor for its use, especially in aquatic environments, since the organic solvents commonly used to solubilize this substance can have toxic effects on aquatic biota. Thus, the aim of the present study was to test the potassium salt of usnic acid (potassium usnate) with regard to molluscicidal activity and toxicity to brine shrimp (Artemia salina). To obtain potassium usnate, usnic acid was extracted with diethyl ether isolated and purified from the lichen Cladonia substellata. Biological assays were performed with embryos and adult snails of B. glabrata exposed for 24 h to the usnate solution solubilized in dechlorinated water at 2.5; 5 and 10 µg/ml for embryos, 0.5; 0.9; 1;5 and 10 µg/ml for mollusks and 0.5; 1; 5; 10 µg/ml for A. salina. The lowest lethal concentration for the embryos and adult snails was 10 and 1 µg/ml, respectively. No toxicity to A. salina was found. The results show that modified usnic acid has increased solubility (100%) without losing its biological activity and may be a viable alternative for the control of B. glabrata.

Synthesis of new 4-amino-2,6-diarylpyrimidine-5-carbonitriles

A facile synthesis of the title compounds 5a–e, from appropriate amidines and benzylidenemalononitriles, is described.

Synthesis of new 1,2,4-oxadiazoles carrying (1'S,2'S)-t-butyloxycarbonyl-1-amino-2- methyl-1-butyl and (1'S)-t-butyloxycarbonyl-1'-amino-1'-ethyl groups at C-5

A facile and efficient synthesis of 3-aryl-5-[(1S)-t-butyloxycarbonyl-1-amino-(2 S)-methyl-1-butyl)]-1,2,4-oxadiazoles 4a-f and 3-phenyl-5-[(1S)-t-butyloxycarbonyl-1-amino-1-ethyl]-1,2,4 -oxadiazole 6 starting from arylamidoximes, N-t-Boc-L-isoleucine and N-t- Boc-L-alanine is decribed. The structures of the intermediates and final compounds have been deduced from spectroscopic data.

Atividade antimicrobiana de derivados fenólicos do líquen Ramalina sorediosa (B. de Lesd.) Laundron

The antimicrobian activity of crude extracts from Ramalina sorediosa was detected by the diffusion disc-paper method. Two phenolic compounds from the lichen considered active were detected by using biochromathograhyc technique. Two of those compounds were identified through thin layer chromatographic technique (TLC) as been usnic acid and the second one, wich is present in higher concentration when compared with the other substances, was the homosekikaik acid. The TLC and high-pressure liquid chromatography (HPLC) assays still detected the salazanic acid presence. The obtained data make it possible to attribute the antibiotic activity of this species to a synergic association of those two substances.

Produção de compostos fenólicos a partir de células imobilizadas do líquen Parmotrema andinum (Müll. Arg.) Hale e avaliação de atividade antimicrobiana

A utilizacao de metabolitos secundarios obtidos de liquens, na industria farmaceutica, de cosmetico, textil e de alimentos deve ser criteriosa, visto que a extracao e isolamento desses metabolitos requerem uma grande quantidade de biomassa dificilmente renovavel, devido ao crescimento lento do liquen. Atualmente, e possivel obter substâncias liquenicas tanto por cultivo de tecidos, como por imobilizacoes celulares e enzimaticas, a partir do talo in natura, utilizando pequena quantidade de material liquenico. Portanto, este trabalho objetiva investigar a producao de compostos fenolicos a partir de celulas imobilizadas de Parmotrema andinum (Mull. Arg.) Hale utilizando acetato de sodio como precursor da biossintese dos fenois. Ensaios de atividade antimicrobiana com extratos orgânicos do talo in natura, eluatos celulares e do acido lecanorico isolado de P. andinum Hale demonstraram acao contra bacterias Gram-positivas. Atraves de testes biocromatograficos foi possivel associar a atividade antibacteriana ao acido lecanorico e uma substância nao identificada presente na especie. As substâncias produzidas atraves de imobilizacao celular nao exibiram acao inibitoria frente os microrganismos testados.

Synthesis of 4-amino-2,6-diaryl-5-cyanopyrimidines as antimicrobial agents

ABSTRACT This article describes an efficient and facile synthesis of 11 2,4,6-trisubstituted 5-cyanopyrimidines starting from meta- and para-substituted 2-cyanocinnamonitriles and arylamidines. The synthesized heterocycles, 3a–k, were characterized by infrared (IR), 1H NMR, 13C NMR, and mass spectral data. The probable mechanism of formation of the title compounds employing 2-cyanocinnamonitriles and arylamidines in the presence of a base was clarified. A preliminary screening of the antibacterial tests clearly showed that 4 out of 11 pyrimidines, 3a, 3e, 3f, and 3k, were effective against bacteria Staphyloccus aureus, Bacillus subtillis, and Pseudomonas aeruginosa. Further, the minimum inhibitory concentration (MIC) against the bacteria has been determined. GRAPHICAL ABSTRACT

Produção de metabólitos bioativos pelo líquen Cladonia substellata Vainio

ABSTRACT – (Production of bioactive metabolites from lichen Cladonia substellata Vainio). This work purposed to make a comparisonbetween antimicrobial activity of crude extracts from Cladonia substellata , collected at Minas Gerais and Para States, Brazil, using thediffusion solid medium methods. Ether, chloroform, and acetone extracts, at 1 mg/mL, 0.1 mg/mL, and 0.01 mg/mL, were tested againsthuman pathogens and phytopathogens. The extracts were submitted to thin layer chromatography and their active p rinciplesattributed by biochromatography. The results demonstrated that the seven fungi species tested were no sensitive to extracts from C. substellata from Para. On the other hand, four of these microorganisms were inhibited by C. substellata extracts from Minas Gerais.All extracts were active to the same bacteria species, but samples from Minas Gerais showed the highest activity. Among the inh ibitedbacteria Staphylococcus aureus was the less sensitive, with an opposite behavior to phytopathogen ones, that showed the highestsensitivity. Chromatographic assays revealed the presence of usnic acid in all extracts, thus in the most content in Para samples. Thebiochromatograms reveals usnic acid as active principle of the species, and a synergic action to norstictic acid found in Minas Geraissamples, what justify its highest activity.

Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (1H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis.

In Vitro and in Vivo Antineoplastic Activity of Barbatic Acid

Background: Lichen compounds exhibit remarkable biological activity. Several of them are potent anticancer agent and some with low or none toxicity. The aim of this study was perform in vitro and in vivo assessments of the antineoplastic activity of organic extract and barbatic acid (BAR) isolated from the lichen Cladia aggregata (Sw.) Nyl. Methods: In vitro assays were performed with both extract and BAR against HEp-2 (Adenocarcinoma of the Larynx), NCI-H292 (Squamous Cell Lung Carcinoma) and KB (Nasopharyngeal Squamous Cell Carcinoma) cells. The tests were carried out on the Sarcoma-180 BAR, tumor and organs were analyzed histopatologically after 7 days of chemotherapy. Results: Cytotoxic tests with BAR revealed 50% inhibitory concentration (IC 50 ) of 19.06 µg mL -1 for NCI-H292 and 12.0 µg mL -1 for KB and 6.25 µg mL -1 for HEp-2 cells. Tests with Sarcoma-180 demonstrated 46.3% inhibitory activity against the tumor by BAR. This substance showed no significant effect on the expression of argyrophilic nucleolar organizer regions proteins (AgNORs). The histopathology study of neoplastic tissue, demonstrated that cell proliferation was not affected by the antineoplastic action of the compound tested. Conclusions: The results indicate that barbatic acid exhibits significant antineoplastic activity and low toxicity rate.

A SIMPLE APPROACH FOR THE SYNTHESIS OF 2,6-DIARYL-4-OXO-3,4-DIHYDROPYRIMIDINE-5-CARBONITRILES

A concise, facile and straightforward synthesis of 2,6-diaryl-4-oxo-3,4-dihydropyrimidine-5carbonitriles 12a-h is reported. The reaction for this preparation involves the condensation of ethyl a cyanocinnamate and its para substituted analogs 8a-e with arylamidines 9a-d under very mild conditions. A probable mechanism of 12a-h from l l a h is proposed. A preliminary pharmacological evaluation of compounds 12c, 12d, 12f e 12h has shown that these compounds possess analgesic activity.