We have optimized the experimental conditions for the silver(I)-promoted oxidative coupling of methyl p-coumarate (I) and methyl ferulate (II), which is the most frequently used methodology to synthesize the bioactive dihydrobenzofuran neolignans 1 ((±)-trans-dehydrodicoumarate dimethyl ester) and 2 ((±)-trans-dehydrodiferulate dimethyl ester). Most of the tested conditions affected the conversion (i.e., the consumption of I and II) and the selectivity (i.e., the percentage of I and II that was converted into 1 and 2, respectively), so the optimized conditions were the ones that afforded the best balance between conversion and selectivity. Silver(I) oxide (0.5 equiv.) is the most efficient oxidant agent amongst the silver(I) reagents that were tested to convert methyl esters I and II into compounds 1 and 2, respectively. Acetonitrile, which has not yet been reported as a solvent for this reaction, provided the best balance between conversion and selectivity, besides being “greener” than other solvents that are more often employed (e.g., dichloromethane and benzene). Under the optimized conditions, the reaction time decreased from 20 to 4 h without significantly impacting the conversion and selectivity.

Copaifera species (Fabaceae) comprises approximately 70 species of large trees, from which 16 can be found in Brazil. The oleoresins obtained from their trunk are widely used in Brazilian folk medicine, which display important antitumoral potential. Chemically, these oleoresins are mainly composed of a mixture of sesquiterpenes and diterpenes. In this paper we are describing the isolation and identification of 12 already known terpenes from oleoresins obtained from three different Copaifera species (C. multijuga, C. pubiflora and C. trapezifolia) and 2 novel diterpenes (ent-16-hidroxy-3,13 clerodadien-15,18-dioic acid and ent-labda-5,13-dien-15-oic acid) from C. trapezifolia. Both new compounds were identified by nuclear magnetic resonance (NMR) spectroscopic (1H and 13C NMR, correlation 1H-1H (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)) and by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) analyses. The cytotoxic potential of these oleoresins, their main non-volatile compounds and their volatile compound fractions were evaluated against a panel of tumoral (MCF-7, ACP01, A549, HeLa) and normal cell lines (MCF-10A, GM07492-A) through XTT (tetrazolium salt) and SRB (sulforhodamine B) assays. The novel diterpene ent-labda-5,13-dien-15-oic acid displayed relevant cytotoxic effect against most of the cancer cell lines with mean inhibitory concentration (IC50) values ranging from 3.57 ± 1.12 to 22.56 ± 1.03 µg mL-1, and a high selectivity level in both assays.

ABSTRACT Abnormal multiplication of oral bacteria causes dental caries and dental plaque. These diseases continue to be major public health concerns worldwide, mainly in developing countries. In this study, the chemical composition and antimicrobial activity of the essential oil of Vitex agnus-castus leaves (VAC‒EO) collected in the North of Brazil against a representative panel of cariogenic bacteria were investigated. The antimicrobial activity of VAC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by using the broth microdilution method in 96-well microplates. The chemical constituents of VAC-EO were identified by gas chromatography (GC‒FID) and gas chromatography‒mass spectrometry (GC‒MS). VAC‒EO displayed some activity against all the investigated oral pathogens; MIC values ranged from 15.6 to 200 μg/mL. VAC-EO had promising activity against Streptococcus mutans (MIC= 15.6 μg/mL), Lactobacillus casei (MIC= 15.6 μg/mL), and Streptococcus mitis (MIC= 31.2 μg/mL). The compounds 1,8-cineole (23.8%), (E)-β-farnesene (14.6%), (E)-caryophyllene (12.5%), sabinene (11.4%), and α-terpinyl acetate (7.7%) were the major chemical constituents of VAC‒EO. VAC-EO displays antimicrobial activity against cariogenic bacteria. The efficacy of VAC-EO against S. mutans is noteworthy and should be further investigated.

In this work we present a complete proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectral analysis of two synthetic dihydrofuran neolignans (±)-trans-dehydrodicoumarate dimethyl ester and (±)-trans-dehydrodiferulate dimethyl ester. Unequivocal assignments were achieved by 1H NMR, proton decoupled 13C (13C{1H}) NMR spectra, gradient-selected correlation spectroscopy (gCOSY), J-resolved, gradient-selected heteronuclear multiple quantum coherence (gHMQC), gradient-selected heteronuclear multiple bond coherence (gHMBC) and nuclear Overhauser effect spectroscopy (NOESY) experiments. All hydrogen coupling constants were measured, clarifying all the hydrogen signals multiplicities. Computational methods were also used to simulate the 1H and 13C chemical shifts and showed good agreement with the trans configuration of the substituents at C7 and C8.

Descrevemos a síntese assistida por micro-ondas de dez derivados de 3-metoxicarbonil-γ-butirolactona e a avaliação in vitro da atividade leishmanicida desses compostos contra formas promastigotas de Leishmania amazonensis. A síntese forneceu a maioria dos compostos com 80-95% de rendimento e as reações duraram cerca de 10-20 min. A maior parte dos compostos apresentaram valores de IC50 superiores a 400 uM. Os compostos 5 (trans-3-(p-metoxi)benzil-4-metil-3-metoxicarbonil-γ-butirolactona) e 10 (trans-3-(p-metoxi)benzil-4-benzil-3-metoxicarbonil-γ-butirolactona) foram as exceções, pois exibiram valores de IC50 de 170,4 e 179,6 µM, respectivamente, o que sugere que a atividade leishmanicida das 3-metoxicarbonil-γ-butirolactonas pode estar relacionada com a natureza e o tamanho do substituinte na posição C-4.

We describe the microwave-assisted synthesis of ten 3-methoxycarbonyl-γ-butyrolactone derivatives and evaluate their in vitro antileishmanial activity against promastigote forms of Leishmania amazonensis. The synthesis furnished most of the compounds in 80-95% yield and reactions lasted about 10-20 min. Most of the compounds displayed IC50 values higher than 400 µM. Compounds 5 (trans-3-(p-methoxy)benzyl-4-methyl-3-methoxycarbonyl-γ-butyrolactone) and 10 (trans-3-(p-methoxy)benzyl-4-benzyl-3-methoxycarbonyl-γ-butyrolactone) were the exceptions: they displayed IC50 values of 170.4 and 179.6 µM, respectively, suggesting that the leishmanicidal activity of 3-methoxycarbonyl-γ-butyrolactones may be related to the nature and size of the substituent at position C-4.

This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of b-amyrin, a-amyrin, and b-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis.

The in vitro schistosomicidal effects of the essential oil obtained from Tagetes erecta L. Asteraceae, leaves (TE-EO) collected in Brazil against Schistosoma mansoni worms are reported in this paper. The oil caused a significant decrease in the motor activity at 50 µg/mL as minimal concentration after 24 h. This oil also caused death of all the parasites and the separation of coupled pairs into individual male and female at 100 µg/mL after 24 h. The viability of adult worm groups treated with the TE-EO at 100 µg/mL was similar to that of groups treated with praziquantel (positive control). In addition, the oil promoted the inhibition of eggs development at all the tested concentrations. These data indicate that the TE-EO could be considered as a promising source for the development of new schistosomicidal agents.

A atividade antimicrobiana de Aegiphila sellowiana Cham., Lamiaceae, contra patógenos da cavidade bucal foi avaliada empregando-se o método de microdiluição em caldo, segundo o protocolo CLSI M7-A7, utilizando-se clorexidina como controle positivo. O extrato etanólico bruto das partes aéreas de A. sellowiana, obtido por maceração, exibiu atividade contra os microrganismos testados neste trabalho, entretanto, os valores de CIM (concentração inibitória mínima) aumentaram após a partição com n-hexano, diclorometano e acetato de etila. Entre as frações testadas, a fração n-hexânica foi a mais efetiva contra os patógenos bucais avaliados, com valores de CIM entre 140 e 350 µg/mL-1. Dados obtidos por CG-EM revelaram que ésteres de ácidos graxos, esteróides e hidrocarbonetos sesquiterpênicos alifáticos são os constituintes majoritários desta fração. Embora esses compostos possam ser os responsáveis pela atividade da fração n-hexânica, outros constituintes químicos presentes nas frações em diclorometano, acetato de etila e hidroalcoólica podem potencializar suas atividades no extrato bruto.

The antimicrobial activity of Aegiphila sellowiana Cham., Lamiaceae, against oral pathogens is reported. The Minimal Inhibitory Concentrations (MICs) for inhibiting the microorganisms growth were determined using the broth microdilution method from the CLSI M7-A7 protocol. Chlorhexidine was used as the positive control. The ethanol crude extract of the aerial parts of A. sellowiana exhibited activity against the microorganisms tested in this work; however, the activity decreased after partition with n-hexane, dichloromethane, and ethyl acetate. Among the tested fractions, the n-hexane fraction was found to be the most effective against the evaluated oral pathogens. GC-MS analysis of this latter fraction revealed that fatty acids esters, steroids, and aliphatic sesquiterpene hydrocarbons are its major constituents. These compounds may be responsible for the activity of the n-hexane fraction, but other chemical constituents of the dichloromethane, ethyl acetate, and hydroalcoholic fraction may potentialize their activities in the crude extract.

Dois novos alcalóides indólicos com esqueleto plumerano, spruceanuminas A (1) e B (2), e oito alcalóides indólicos conhecidos, aspidospermidina (3), desmetoxipalosina (4), aspidocarpina (5), aspidolimina (6), fendlerina (7), aspidolimidina (8), obscurinervidina (9) e obscurinervina (10), foram isolados do extrato metanólico das cascas do caule e sementes de Aspidosperma spruceanum. As estruturas dos compostos foram elucidadas com base na análise de dados espectroscópicos, principalmente os obtidos por espectros de RMN ¹H e 13C (1D e 2D) e por espectrometria de massas.

Two novel indole alkaloids with plumeran skeleton, spruceanumines A (1) and B (2), and eight known indole alkaloids, aspidospermidine (3), demethoxypalosine (4), aspidocarpine (5), aspidolimine (6), fendlerine (7), aspidolimidine (8), obscurinervidine (9) and obscurinervine (10) were isolated from stem bark and seeds methanolic extracts of Aspidosperma spruceanum. Compounds structures were elucidated on the basis of spectroscopic data, mainly those obtained by ¹H and 13C NMR (1D and 2D) and mass spectrometry.

The field of application of mass spectrometry (MS) has increased considerably due to the development of ionization techniques. Other factors that have stimulated the use of MS are the tandem mass spectrometry (MS/MS) and sequential mass spectrometry (MSn) techniques. However, the interpretation of the MS/MS and MSn data may lead to speculative conclusions. Thus, various quantum chemical methods have been applied for obtaining high quality thermochemical data in gas phase. In this review, we show some applications of computational quantum chemistry to understand the formation and fragmentation of gaseous ions of organic compounds in a MS analysis.

O padrão de fragmentação de uma série homóloga de alcalóides piperidínicos isolados de Senna spectabilis foi investigado utilizando-se espectrometria de massas tandem com ionização por electrospray (ESI-EM/EM). A análise dos extratos EtOH e frações das flores e dos frutos de S. spectabilis por ESI-EM e ESI-EM/EM permitiu elucidar a estrutura de quatro componentes pertencentes a uma série homóloga destes alcalóides, bem como de quatro co-metabólitos inéditos. A elucidação estrutural dos co-metabólitos, com base no padrão de fragmentação de alcalóides piperidínicos previamente isolados, e confirmados pelos dados de EM de alta resolução, demonstra a importância desta técnica para a determinação do "perfil metabolômico" de uma espécie de importância farmacológica.

The fragmentation pattern of a homologous series of piperidine alkaloids isolated from S. spectabilis was investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS). The ESI-MS and ESI-MS/MS analyses of EtOH extracts and fractions from flowers and fruits of S. spectabilis allowed to elucidate the structures of four new compounds. The identification of these co-metabolites, based on the fragmentation patterns of previously isolated compounds, and further confirmed by accurate mass spectrometry defines this technique as a powerful tool to determine the "metabolomic profile" of species which has pharmacological importance.