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Abstract: Antibiotic resistance can be characterized, in biochemical terms, as an antibiotic’s inability to reach its bacterial target at a concentration that was previously effective. Microbial resistance to different agents can be intrinsic or acquired. Intrinsic resistance occurs due to inherent functional or structural characteristics of the bacteria, such as antibiotic-inactivating enzymes, nonspecific efflux pumps, and permeability barriers. On the other hand, bacteria can acquire resistance mechanisms via horizontal gene transfer in mobile genetic elements such as plasmids. Acquired resistance mechanisms include another category of efflux pumps with more specific substrates, which are plasmid-encoded. Efflux pumps are considered one of the main mechanisms of bacterial resistance to antibiotics and biocides, presenting themselves as integral membrane transporters. They are essential in both bacterial physiology and defense and are responsible for exporting structurally diverse substrates, falling into the following main families: ATP-binding cassette (ABC), multidrug and toxic compound extrusion (MATE), major facilitator superfamily (MFS), small multidrug resistance (SMR) and resistance-nodulation-cell division (RND). The Efflux pumps NorA and Tet(K) of the MFS family, MepA of the MATE family, and MsrA of the ABC family are some examples of specific efflux pumps that act in the extrusion of antibiotics. In this review, we address bacterial efflux pump inhibitors (EPIs), including 1,8-naphthyridine sulfonamide derivatives, given the pre-existing knowledge about the chemical characteristics that favor their biological activity. The modification and emergence of resistance to new EPIs justify further research on this theme, aiming to develop efficient compounds for clinical use.

Nos processos de regulação das relações entre a sociedade, os sistemas socioculturais, natureza e o meio ambiente, a gestão de recursos naturais surge como sendo um elemento essencial. Nesta esteira, a perda da diversidade biológica torna-se então um problema crítico para a existência humana, devido ao fato que a extinção de espécies é irreversível representando a perda de um genoma que é único. Estudos para conhecimento das espécies nativas com potencial terapêutico ganham grande relevância. Nesta abordagem encontram-se as pesquisas com extratos e óleos essenciais de espécies nativas. Conhecer a composição química e possíveis atividades biológicas, relacionadas com os extratos e constituintes voláteis advindos de recursos naturais nativos, amplia a possibilidade de criação de protocolos de uso sustentável da biodiversidade. Neste artigo abordou-se a constituição da REBIFLORA – Rede de Bioprospecção e Inovação na Floresta Atlântica, sua atuação nos estados do Paraná e Santa Catarina, visando contribuir para o entendimento acerca da composição química e a atividade biológica, relacionadas às espécies nativas e potencialidade de agregar valor aos produtos da biodiversidade.

a Universidade Regional do Cariri, URCA, Cel Ant^onio Luis, 1161, 63105-000, Pimenta, Crato, CE, Brazil b Universidade Federal do Paran a, UFPR, XV de Novembro, 1299, 80.060-000, Centro, Curitiba, PR, Brazil c Universidade Regional de Blumenau, FURB, Ant^onio da Veiga, 140, 89030-903, Itoupava Seca, Blumenau, SC, Brazil d Laborat orio de investiga¸c~ao em Gen etica e Hematologia Translacional, Instituto Gon¸calo Moniz (IGM), Funda¸c~ao Oswaldo Cruz (FIOCRUZ), Salvador, BA 40296- 710, Brazil e Centro Universit ario Doutor Le~ao Sampaio (Unile~ao), Av. Maria Leticia Leite Pereira s/n, Lagoa Seca, Juazeiro do Norte, Brazil

Aiming to valorise the Atlantic Rainforest biodiversity in Santa Catarina, the chemical characterisation of the essential oils (EOs) from leaves of Vernonanthura montevidensis (Spreng.) H. Rob. is described for the first time. Fresh leaves collected in the year 2014 and 2015, were submitted to hydrodistillation to give pale blue EOs in yields of 0.21 and 0.19%, respectively. The EOs were characterised by GC-MS and GC-FID semi- and quantitative methods. The monoterpene β-pinene was the major constituent in both samples reaching a maximum of 26.3%. The monoterpene α-pinene and the sesquiterpene β-caryophyllene, were also among the major constituents in both samples. By means of the extracted ion chromatogram procedure, it was possible to detect chamazulene, which was associated with the pale blue colour of the essential oils. In the in vitro antimollicute assays, the essential oil was moderately active against Mycoplasma genitalium and M. pneumoniae with MIC values of 250 µg mL−1.

This study aimed to evaluate the intrinsic antibacterial activity and antibiotic-enhancing effect of an arylamino methylene derivative (MAD) in association with fluoroquinolones. The antibacterial activity against multiresistant Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli was analyzed by determining the minimum inhibitory concentration (MIC) using the broth micro dilution method. A reduction in the MIC of the fluoroquinolones against strains treated simultaneously with the MAD was interpreted as an enhanced antibiotic activity. While the MAD exhibited no clinically effective action (MIC ≥ 1.024 µg/mL), it was found to significantly potentiate the activity of norfloxacin, ofloxacin and lomefloxacin against all the strains, which may be related to structural similarities between the MAD and quinolones. Our findings suggest that Meldrum’s acid arylamino derivatives may represent promising molecules in the elaboration of new drugs to reverse resistance to fluoroquinolones.

Aiming to valorise the Atlantic Rainforest biodiversity in Santa Catarina, the chemical characterisation of the essential oils (EOs) from leaves of

Objective Efflux pumps are transmembrane proteins associated with bacterial resistance mechanisms. Bacteria use these proteins to actively transport antibiotics to the extracellular medium, preventing the pharmacological action of these drugs. This study aimed to evaluate in vitro the antibacterial activity of 1,8-naphthyridines sulfonamides, as well as their ability to inhibit efflux systems of Staphylococcus aureus strains expressing different levels of the NorA efflux pump. Methods The broth microdilution test was performed to assess antibacterial activity. Efflux pump inhibition was evaluated in silico by molecular docking and in vitro by fluorometric tests, and the minimum inhibitory concentration (MIC) was determined. The MIC was determined in the association between 1,8-naphthyridine and norfloxacin or ethidium bromide. Results The 1,8-naphthyridines did not show direct antibacterial activity. However, they effectively reduced the MIC of multidrug-resistant bacteria by associating with norfloxacin and ethidium bromide, in addition to increasing the fluorescence emission. In silico analysis addressing the binding between NorA and 1,8-naphthyridines suggests that hydrogen bonds and hydrophilic interactions represent the interactions with the most favourable binding energy, corroborating the experimental data. Conclusion Our data suggest that 1,8-naphthyridines sulfonamides inhibit bacterial resistance through molecular mechanisms associated with inhibition of the NorA efflux pump in S. aureus strains.

Piper mikanianum from Santa Catarina, southern Brazil, is a well known source of safrole, an arylpropanoid precursor of several bioactive molecules. This work determined the seasonal and hydrodistillation time influence on the essential oil (EO) yield and composition. Dehydrated leaves were hydrodistilled with and without fractioning during a total period of 240 min. The EO yields varied from 0.66-0.84% with the highest values been observed during spring and summer seasons. The highest concentration of safrole was found in the winter oil (81%). In the fractioning experiments the concentration of safrole varied from 75-80% in F1 (oil distilled during 60 min) and 42-64% in F2 (oil distilled between 60-240 min).

The commercialisation of the biorefinery approach involving the integration of the multi-step valorisation of low value biomass feedstock into a variety of chemicals, fuels and bioproducts is still very limited. In this context, the present work proposes an advanced methodology that comprises a cascaded approach towards wheat straw valorisation. The studied concept lies in the employment of an aqueous solution of the acidic 1-ethyl-3-methylimidazolium hydrogen sulfate ionic liquid in a selective and efficient hydrolysis of the hemicellulose fraction of wheat straw into pentoses, namely xylose and arabinose. An experimental design was utilised to search for the optimisation parameters, resulting in a maximum 80.5 wt% pentose yield in the liquor. Furthermore, the remaining solid, which contained practically all of the initial cellulose and lignin, was processed by considering two scenarios: (i) a direct enzymatic hydrolysis of the reaction solid, which yielded 75.8 mol% glucose; or (ii) a preceding extraction of lignin followed by enzymatic saccharification of the cellulose pulp, which yielded 91.3 mol% glucose. For both scenarios, lignin-rich solid fractions were obtained with distinct purities and yields. Additionally, the second scenario allowed producing a stream of value-added aromatic (phenolic) compounds. This work also overcame the challenges in IL recycling and reuse, with a simultaneous recovery of the pentoses from the reaction liquor as high as 88.6 mol%. info:eu-repo/semantics/publishedVersion

The secular use of plants in popular medicine has emerged as a source for the discovery of new compounds capable of curing infections. Among microbial resistance to commercial drugs, species such as Piper diospyrifolium Kunth, which are used in popular therapy, are targets for pharmacological studies. With this in mind, antimicrobial experiments with the essential oil from the P. diospyrifolium (PDEO) species were performed and its constituents were elucidated. The oil compounds were identified by gas chromatography coupled to mass spectrometry (GC/MS). The broth microdilution method with colorimetric readings for bacterial tests (Escherichia coli and Staphylococcus aureus) and spectrophotometric readings for fungal tests (Candida albicans and Candida tropicalis), whose data were used to create a cell viability curve and calculate its IC50 against fungal cells, were used to determine the minimum inhibitory concentration of the oil and its combined action with commercial drugs. The oil's minimal fungicidal concentration and its action over fungal morphological transition were analyzed by subculture and microculture, respectively. Chemical analysis revealed Z-Carpacin, Pogostol and E-Caryophyllene as the most abundant compounds. Results from the intrinsic analysis were considered clinically irrelevant, however the oil presented a synergistic effect against multiresistant E. coli and S. aureus strains when associated with gentamicin, and against the standard and isolated C. tropicalis strains with fluconazole. A fungicidal effect was observed against the C. albicans isolate. Candida spp. hyphae inhibition was verified for all strains at the highest tested concentrations. The P. diospyrifolium essential oil presented a promising effect when associated with commercial drugs and against a fungal virulence factor. Thus, the oil presented active compounds which may help the development of new drugs, however, new studies are needed in order to clarify the oil's mechanism of action, as well as to identify its active constituents.

This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum's acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5‑chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10a); 2,5-dichloro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4‑bromo-2,5-difluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.

Naphthyridines represent a class of heterocyclic compounds formed by two condensed aromatic rings. This study aimed to evaluate the antibacterial activity and in vitro inhibition of efflux resistance mechanisms of a series of 1,8-naphthyridine sulfonamides against strains carrying Tet(K) and MsrA efflux pumps. The efflux pump inhibitory capacity was evaluated by analyzing synergistic effects between 1,8-naphthyridine sulfonamides and standard antibiotics, as well as ethidium bromide. The following 1,8-naphthyridines were used: 4-methyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 1); 2,5-Dichloro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 2); 2,3,4-trifluoro-N-(5-chloro-1,8-naphthyridin-2-yl)benzenesulfonamide (Naph 7); 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 9). The 1,8-naphthyridine sulfonamide derivatives possessed a potential Tet(K) and MsrA efflux pump inhibitory action.

Gas chromatography–mass spectrometry (GC–MS) analysis of Aloysia gratissima (Gill. et Hook) Tronc. essential oil obtained by hydrodistillation lead to the identification of twenty-two compounds. The major compounds found in this study were 1,8-cineole (13.7%), germacrene D (13.4%), β-caryophyllene (12.7%) and β-pinene (11.7%). The oil demonstrated antibacterial and antifungal activities against mainly Bacillus cereus and Trichophyton mentagrophytes. Aloysia gratissima oil was also screened for its antioxidant activity by 2,2-diphenylpicrylhydrazyl (DPPH) free radical; however, it was less effective than butylated hydroxytoluene (BHT). These findings suggest feasible application of A. gratissima essential oil as an antimicrobial agent and its chemical characteristic may lead to the extraction of active compounds in isolated or combined forms with useful applications.

The Piper mikanianum species were investigated by the antimicrobial potential and chemical composition. Chemical analysis was performed by gas chromatography coupled to mass spectrometry (GC/MS). The Minimum Inhibitory Concentration (MIC) as well as the 50% Inhibitory Concentration against Candida strains were determined by microdilution. The effect of the drug-oil combination was also evaluated to verify possible synergism. The Minimum Fungicidal Concentration (MFC) was evaluated by subculturing the microdilution in Petri dishes and the anti-pleomorphism potential of the oil was tested in humid chambers. Chemical analysis revealed safrol as the major compound. The results from the intrinsic activity evaluation of the oil did not reveal a clinical importance, however, it presented a synergistic effect when associated with gentamicin against the multidrug resistant E. coli strain and when associated with fluconazole against fungal strains. Moreover, the oil possessed a fungistatic effect. Total inhibition of filamentous structures occurred in both Candida species in the anti-virulence test. The P. mikanianum essential oil showed a potentiating activity of drugs for which resistance exists and an inhibitory effect of one of the main virulence factors of the Candida genus, morphological transition, which has been previously shown to be responsible for causing invasive infections in human tissues.

Due to the biological properties associated to the Baccharis genus and the limited information on its antimicrobial properties, the present work investigates the chemical composition and antibacterial, antifungal and antiprotozoal activities of the essential oils of two species, B. uncinella from Campo Alegre and B. semiserrata from Atalanta, both places located in Santa Catarina State, Southern Brazil. Oils were obtained by hydrodistillation and were analyzed by gas chromatography–flame ionization detector (GC–FID) and GC–mass spectrometry (GC–MS). The dry leaf essential oil yield from B. uncinella was 0.65% (m/m), and 0.50% and 0.22% (m/m) for dry leaf and twig from B. semiserrata, respectively. The main components in the oil from B. uncinella were α-pinene (9.0%), β-pinene (9.2%), limonene (11.5%), β-caryophyllene (13.2%) and spathulenol (9.3%). The following major compounds were identified in the leaf essential oil from B. semiserrata: α-pinene (4.3%), β-pinene (11.4%), limonene (6.7%), β-caryophyllen...

In our continuous search for naturally occurring compounds of scientific and technological relevance, the chemical composition and antibacterial activity of the essential oils of two populations of Piper xylosteoides from Santa Catarina, Brazil, is described. Both oils showed a very high safrole concentration, being the highest value associated to the sample collected in Orleans (84.1%). As the second major compound, the monoterpene α-pinene was present with the highest concentration (15.3%) in the Sao Bonifacio sample. The antibacterial activity was examined towards both Gram-positive and Gram-negative bacteria. The oils showed weak activity against the bacteria tested. This species can be considered a new economically important natural source of the arylpropanoid safrole.

Two 1,8-naphthyridines were synthesized and found to be fluorescent in solution. These compounds were studied in the presence of Cu + and Cu 2+ ions and it was verified that the metal causes the quenching of their fluo- rescence emission, due to the formation of complexes be- tween the naphthyridine and the metal. A displacement assay was carried out in a DMSO-water mixture with the addition of various anions to the solutions of the complexes, and it was observed that these systems have a high capacity to selectively detect cyanide.

The present paper reports the synthesis and antiprotozoal activity of N-quinolin-8-yl-arylsulfonamides and their copper and zinc complexes. Sulfonamides 2-5 were synthesized by reacting 8-aminoquinoline with several commercial arylsulfonyl chlorides. The corresponding complexes 6-13 were obtained using copper (II) acetate or zinc chloride in methanol. In vitro activity was carried out against promastigote forms of Leishmania braziliensis and L. chagasi, and epimastigote forms of Trypanosoma cruzi. Selected compounds were tested against axenic amastigote forms of L. braziliensis. The new 2,5-dichlorobenzenesulfonamide ligand was found to be inactive under the selected bioassays, however its copper complex 8 was active with the highest selective indexes (SI) against L. braziliensis promastigote and amastigote forms, with IC50 values of 2.59 and 0.35 μM, respectively. Difluorinated copper 10 and zinc 11 complexes were most active against L. braziliensis, with IC50 of 1.11 μM and 1.25 μM, respectively. However, the SI values were about 12 for both compounds. In general, the complexation of sulfonamides increases the antiprotozoal activity, as well as the cytotoxicity on Vero cells. These results confirm the antiprotozoal potential of sulfonamides and metal-based sulfonamides.

We have investigated the effects of phosphate fertilization and inoculation with isolates of arbuscular mycorrhizal fungi Scutellospora heterogama SCT120E, Gigaspora decipiens SCT304A, Acaulospora koskei SCT400A, Entrophospora colombiana SCT115, and an assemblage (Mix) of all four isolates on growth, development and oleoresin production of micropropagated Zingiber officinale. After 120 and 210 d of growth, the Mix and phosphorus addition significantly increased shoot height relative to control plants. Phosphorus addition was the only treatment resulting in significantly large shoot dry biomass relative to control after 120 d. No statistical differences were observed between treatments for shoot dry biomass after 210 d and for fine and coarse root biomass at both harvests. Inoculation with S. herogama and G. decipiens resulted in larger yields of oleoresin, corresponding to 3.48% and 1.58% of rhizome fresh biomass respectively. Based on retention index and mass spectrometry, we have characterized the following constituents present in ginger rhizomes: ar-curcumene, zingiberene, γ-cadinene, bisabolene, δ- or α-cadinene and farnesol. Two other constituents were characterized as possible members of the gingerol class. Results suggest that the screening and inoculation of arbuscular mycorrhizal fungi in ginger plants is a feasible procedure to increase the oleoresin production of Z. officinale and consequently increase the aggregate value of ginger rhizome production. Avaliou-se o efeito da adubação fosfatada e da inoculação de isolados de fungos micorrízicos arbusculares [Scutellospora heterogama SCT120E, Gigaspora decipiens SCT304A, Acaulospora koskei SCT400A, Entrophospora colombiana SCT115 e uma mistura (Mix) de todos os quatro isolados] sobre o crescimento e desenvolvimento vegetativo e produção de óleo-resina em plantas micropropagadas de gengibre (Zingiber officinale). Verificou-se que, aos 120 e 210 d após o cultivo, as plantas dos tratamentos Mix e sob adição de fósforo tiveram maior altura em relação às plantas-controle. A adição de fósforo foi o único tratamento que resultou em aumento significativo na biomassa seca da parte aérea relativamente ao tratamento-controle, após 120 d de cultivo. A biomassa seca da parte aérea, aos 120 d, bem como a biomassa de raízes finas e grossas, aos 120 e 210 d, não responderam aos tratamentos aplicados. A inoculação com S. herogama e G. decipiens foram os únicos tratamentos que proporcionaram incrementos significativos de produção de óleo-resina, respectivamente 3,48 e 1,58% em relação à biomassa fresca de rizomas de gengibre. Baseado no índice de retenção e espectrometria de massa, caracterizaram-se os seguintes constituintes presentes nos rizomas de gengibre: ar-curcumeno, zingibereno, γ-cadineno, bisaboleno, δ- ou α-cadineno e farnesol. Outros dois constituintes foram caracterizados como possíveis membros da classe dos gingeróis. Os resultados sugerem que a seleção e a inoculação de fungos micorrízicos arbusculares em plantas de gengibre é uma alternativa viável para aumentar a produção de óleo-resinas e, conseqüentemente, aumentar o valor agregado da produção de rizomas nessa espécie.

This work describes the antimicrobial, antioxidant and anticholinesterase activities in vitro of organic extracts from fourteen seaweeds, eleven sponges, two ascidians, one bryozoan, and one sea anemone species collected along the Brazilian and Spanish coast, as well as the isolation of the diterpene (4R, 9S, 14S)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) and halogenated sesquiterpene elatol (2). The most promising antimicrobial results for cell wall bacteria were obtained by extracts from seaweeds Laurencia dendroidea and Sargassum vulgare var. nanun (MIC 250 μg/ml), and by the bryozoan Bugula neritina (MIC 62.5 μg/ml), both against Staphylococcus aureus. As for antimollicutes, extracts from seaweeds showed results better than the extracts from invertebrates. Almost all seaweeds assayed (92%) exhibited some antimicrobial activity against mollicutes strains (Mycoplasma hominis, Mycoplasma genitalium, Mycoplasma capricolum and Mycoplasma pneumoniae strain FH). From these seaweeds, A1 (Canistrocarpus cervicornis), A11 (Gracilaria sp.) and A4 (Lobophora variegata) showed the best results for M. pneumoniae strain FH (MIC 250 μg/ml). Furthermore, compounds 1 and 2 were also assayed against mollicutes strains M. hominis, M. genitalium, M. capricolum, M. pneumoniae strain 129 and M. pneumoniae strain FH, which showed MIC > 100 μg/ml. Antioxidant activities of extracts from these marine organisms were inactive, except for E7 (from sponge Ircinia sp.), which exhibited moderated antioxidant activities for two methods assayed (IC50 83.0 ± 0.1 μg/ml, and 52.0 ± 0.8 mg AA/g, respectively). Finally, for the anticholinesterase activity, all the 29 samples evaluated (100%) exhibited some level of activity, with IC50

The thermocyclisation of phenylenediamine-bis(methylene Meldrum's acid) derivatives has been investigated. Those of o-phenylenediamines give 1,10-phenanthroline derivatives, while those of m- and p-phenylenediamines lead to the preferential formation of angular diazatricycles. Thus, for example, the di-Meldrum's acid derivative of 2,5-dichloro-1,4-phenylenediamine gives, via ipso-substitution, the unexpected angular product 19.

The title mol­ecule, [Zn(C10H8NO)2(H2O)], lies on a crystallographic twofold axis. The ZnII atom is in a trigonal–bipyramidal coordination geometry formed by two N atoms of two quinoline groups, two O atoms and a water mol­ecule. In the crystal structure, inter­molecular hydrogen bonds link mol­ecules into a two-dimensional network.

The essential oil composition of two Piperaceae from the Itajai Valley in Santa Catarina, Brazil, is described by means of GC and GC/MS analysis. Piper cernuum provided an oil constituted mainly by α-pinene (2.5%), β-elemene (2.6%), β-caryophyllene (4.4%), germacrene D (2.7%), β-dihydroagarofuran (31.0%), elemol (12.0%), 10-epi-γ- eudesmol (13.0%) and β-eudesmol (2.6%). Twenty-eight compounds representing 87.8% of the oil were identified. Peperomia emarginella provided the most interesting oil due to its pleasant and intense odor, where limonene (29.0%) and decanal (33.0%) accounted for 62.0% of the overall composition. Thirty-one compounds representing 94.4% of the oil composition were identified.

The title compound, C 11 H 2 Cl 5 N 3 O, crystallizes in the mono, clinic system with two molecules in the asymmetric unit. The molecules are chemically identical but have different structural parameters. In the three-dimensional packing, the molecules are arranged in dimers that are connected by slipped π-π stacking, and these dimers are connected to one another through several C-H...O and Cl...Cl interactions.

Essential oils have been extensively studied in recent years as a natural source of new antimicrobial agents. In this work, essential oils of leaf and branch from Drimys angustifolia growing in Southern Brazil were obtained by hydrodistillation and analyzed by gas chromatographies with flame ionization detector (GC-FID) and with mass spectrometer (GC-MS). Drimenol and bicyclogermacrene were isolated by column chromatography from branch and leaf essential oils, respectively. Oils, isolated compounds and combinations of them were assayed against Gram-(+) and Gram-(-) bacteria. The oils showed to be more active against Bacillus cereus, with minimum inhibitory concentration (MIC) 125 and 250 µg mL-1 for branch and leaf oils, respectively, strongly inhibiting bacterial growth. Bicyclogermacrene was more active then drimenol, providing a MIC value of 167 µg mL-1 against B. cereus. Synergism was not observed in any of the combinations tested. Nos últimos anos, os óleos essenciais vêm sendo intensamente estudados como fonte natural de novos agentes antimicrobianos. Neste trabalho, os óleos essenciais das folhas e galhos de Drimys angustifolia do sul do Brasil foram obtidos por hidrodestilação e analisados por cromatografias gasosas com detector de ionização de chama (GC-FID) e com espectrômetro de massa (GC-MS). Os constituintes drimenol e biciclogermacreno foram isolados por cromatografia em coluna do óleo essencial dos galhos e folhas, respectivamente. Os óleos, os constituintes isolados e combinações destes foram testados contra bactérias Gram-(+) e Gram-(-). Os óleos essenciais foram mais ativos contra Bacillus cereus, com MIC (concentração inibitória mínima) de 125 e 250 µg mL-1 para os galhos e folhas, respectivamente, inibindo fortemente o crescimento bacteriano. Biciclogermacreno foi mais ativo que drimenol, fornecendo um valor de MIC de 167 µg mL-1 contra B. cereus. Não foi observado qualquer efeito sinérgico nas combinações testadas.

This work reports the chemical composition as well as the antibacterial, antifungal and antiparasitic activities of the leaf essential oil from Piper malacophyllum. The oil was extracted by hydrodistillation and analyzed by GC-FID, GC-MS and polarimetry. Among the 28 compounds identified, (+)-camphor was the major constituent. The essential oil showed activity against most of the microorganisms tested, especially antifungal action, with a MIC of 500 µg mL-1 against Trichophyton mentagrophytes and Cryptococcus neoformans. This is the first study reporting the composition and biological properties of leaf essential oil from P. malacophyllum.

Piper mikanianum (Kunth) Steudel collected from the Atlantic Rainforest at Atalanta in Santa Catarina state, southern Brazil, afforded by hydrodistillation of the fresh leaf oil in 0.65% yield. The oil, which was analyzed by GC and GC/MS, was found to contain a high content of safrole (82%). The identified compounds accounted for 99% of the oil composition. This species can be regarded as a new source of safrole.

Plum (Prunus salicina Lindl. cv. Harry Pickstone), a China indigenous fruit, is widely produced and consumed in countries such as Japan and Brazil. The practice of thinning is common in horticulture and the fruits removed are discarded as waste. Like the great majority of vegetables, these thinning discards also contain essential oils which have not been investigated until the present time. The extraction of the plum thinning discards volatile oil, through the hydrodistillation method, produced a yield of 0.06% (m/m) and a total of 21 components were identified, with 11 of them being responsible for 72,9% of the total oil composition. The major compounds determined through GC and GC-MS were Z-α-bisabolene (13.7%), n-hexadecanoic acid (12.7%), phytol (12.7%), and β-caryophyllene (10.4%).

A short new route to the pyrido[2,3,4-kl]acridine ring system has been developed from readily available quinoline precursors involving two key steps: (i) a palladium(0)-catalysed Suzuki cross-coupling reaction of 4-chloroquinolines with arylboronic acids, and (ii) an intramolecular nitrene insertion reaction of the nitrenes derived from 4-phenyl-5-azidoquinolines.

The palladium-catalysed cross-coupling reactions of arylboronic acids with a variety of π-deficient heteroaryl chlorides proceed in high yield. [1,4-Bis(diphenylphosphino)butane]palladium(II) dichloride was found to be a very satisfactory catalyst for monocyclic heteroaryl chlorides, whereas tetrakis(triphenylphosphine)palladium(O) was found to be excellent for a range of chloroquinoline derivatives.

According to the Health’s World Organization, leishmaniasis and trypanossomiasis are growing problems of public health, being endemic particularly in Latin America. The medicines utilized in the handling of these illnesses were developed many decades ago, and they show a low efficacy and strong side effects. The pyridoquinolines are heterocyclic diazaantracenic compounds that have showed cytotoxic activity. The biological importance of the pyridoquinolines, and the interest in discovering new leishmanicides and trypanocides agents have been stimulating the synthesis of substituted pyrido[2,3–g]quinolines, and the evaluation of their leishmanicide and trypanocide potential. So, this work describes the diazatricicles’s synthesis, using the termociclization’s reaction of the fenilenediaminic bis-adduct of Meldrum’s acid. The 2,5-dimethyl-1,4-bis[(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-ylidenomethyl)amino]-benzene has been obtained in good yield by the condensation of the Meldrum’s acid with the 2,5-dimethyl-1,4-phenylenediamine in trimethylorthoformate. The termociclization in diphenylether has been accompanied for a spontaneous elimination of acetone and carbon dioxide generating the diazatricycle, that has been chlorinated without prior purification with phosphorus oxichloride, giving the 4,9-dichloro-5,10-dimethyl-pyrido[2,3-g]quinoline, in low yield. The nucleophilic substitution’s reaction with the 2-amine-5-diethylaminepentane has been repeated several times in different reaction’s conditions, but we haven’t obtained the expected product, needing the search of new procedures and optimization of the reaction’s conditions. The obtained compounds have been characterized by spectroscopic technicals of IV and RMN 1H. The evaluation of the leishmanicide and trypanocide activity was done for the compound called 4,9-dichloro-5,10-dimethyl-pyrido[2,3-g]quinoline, however it hasn’t even presented any activity

In the present paper 12 N-quinolin-8-yl-arylsulfonamides synthesized by coupling 8-aminoquinolines with various arylsulfonylchlorides were assayed in vitro against Leishmania amazonensis, Leishmania chagasi and Trypanosoma cruzi strains. This series of new compounds were found to be selective for Leishmania spp. promastigote and amastigote forms. The most active compound was the N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide 10 with an IC50 against L. amazonensis and L. chagasi of 2.12 and 0.45 μM, respectively. The less cytotoxic biphenyl derivative 7 was very effective against intracellular L. amazonensis with a reduction of macrophage cell infection of 82.1% at 25 μM. In addition, a copper complex 17 of an inactive ligand was readily synthesized and showed high leishmanicidal and trypanocidal activity against both extra and intracellular forms.

Formigas causam danos e perdas econômicas em florestas plantadas, principalmente em plantios de Pinus taeda, e no seu controle são utilizados agroquímicos que podem contaminar os processos ecológicos, sendo que a busca por formas alternativas de controle destes insetos nas atividades florestais é prática desejável. Entre as várias formas de controle alternativo existentes, como o manejo do habitat e o controle biológico, há o controle com a utilização de extratos e óleos essenciais obtidos de plantas com propriedades inseticidas. O objetivo principal deste estudo foi avaliar o efeito do óleo essencial extraído das folhas de Drimys angustifolia, em colônias de formigas cortadeiras do gênero Acromyrmex spp., em plantio de P. taeda, como alternativa de controle. O óleo essencial foi aplicado em dois tratamentos com concentração de 100% e 10% no interior de oito formigueiros ativos com um pulverizador manual e comparado com quatro formigueiros de controle. O resultado final demonstrou que os oito formigueiros tratados com óleo estavam abandonados, evidenciando a potencial atividade do óleo essencial sobre as formigas, comparado com os formigueiros de controle que se mantiveram ativos. O óleo essencial de D. angustifolia apresentou potencial para ser aplicado como controle alternativo de formigas cortadeiras do gênero Acromyrmex. AbstractEffect of essential oil from leaves of Drimys angustifolia in colonies of Acromyrmex spp. in pinus taeda planting. Ants cause damage and economic losses in plantation forests, mainly in Pinus taeda; their control implies agrochemicals that can contaminate the ecological processes, and the search for alternative ways to control these insects in the forest activities is a desirable practice. Among the various existing alternative forms of control, such as the habitat management and biological control, there is the control with use of extracts and essential oils of plants with insecticidal properties. The main objective of this research was to evaluate the effect of the essential oil extracted from the leaves of Drimys angustifolia, in colonies of leaf cutting ants of the genus Acromyrmex spp., in planting P. taeda, as an alternative control. The essential oil was applied in two treatments with 100% and 10% concentrations within eight active nests with a hand sprayer and compared with four nests as control. The final result showed that the eight nests treated with the oil were abandoned, highlighting the potential activity of the essential oil to ants, compared to control nests that remained active. The essential oil of D. angustifolia exhibited potential to be applied as alternative control of leaf-cutting ants of the genus Acromyrmex.Keywords: Leaf cutting ants; alternative control; extraction by steam distillation; bark-of-anta; secondary metabolites.

The synthesis of 5,6-methylenedioxy-indol-3-yl-methanoic acid 8 and 5,6-methylenedioxy-indol-3-yl-acetic acid 13 is described. Piperonal was employed as starting material, and the construction of the heterocyclic ring based on the Hemetsberger reaction of the corresponding b-azidostyrene was highly regiospecific. Compound 8 was obtained as a key intermediate towards 13, and a Mannich reaction was used to introduce the required alkyl side chain. The route comprised eight steps giving 13 in 26% overall yield. The formation of the indolic ring via reductive cyclisation of o,b-dinitrostyrene is also presented.

The mol­ecular packing of the title compound, C24H30N2O3S, is stabilized by a hydrogen-bonded network. Both sulfonyl O atoms are involved in inter­molecular hydrogen bonds of types N—H⋯O and C—H⋯O. An inter­molecular N—H⋯N hydrogen bond is also observed.

Departamento de Quimica, Instituto de Ciencias Exatas e da Terra, Universidade Federal de Mato Grosso, Cuiaba, 78060-900 Mato Grosso, Brazil Departamento de Quimica, Centro de Ciencias Fisicas e Matematicas, Universidade Federal de Santa Catarina, Campus Trindade, Florianopolis, 88040-900 Santa Catarina, Brazil Departamento de Microbiologia e Parasitologia, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Trindade, Florianopolis, 88040-900 Santa Catarina, Brazil Departamento de Quimica, Centro de Ciencias Exatas e Naturais, Universidade Regional de Blumenau, Blumenau, 89010-971 Santa Catarina, Brazil Clemens Schopf-Institut fur Organische Chemie und Biochemie, Technische, Universitat Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany

A short new route to the pyrido[2,3,4-kl]acridine ring system has been developed from readily available quinoline precursors involving two key steps: (i) a palladium(0)-catalysed Suzuki cross-coupling reaction of 4-chloroquinolines with arylboronic acids, and (ii) an intramolecular nitrene insertion reaction of the nitrenes derived from 4-phenyl-5-azidoquinolines.

The preparation of several amides and hydrazides from the reaction of the title compounds with different nitrogen nucleophiles is shown to be a general high-yield conversion of synthetic utility.