Chalcone-quinolinone hybrid compounds, as well as the synthesis of such compounds, have few reports in the literature. Such compounds may be quite useful in therapeutics, since various biological activities are reported for both chalcones and quinolinones. In the present work, several novel chalcone-quinolinone compounds have been synthesized. The reaction conditions developed allowed to obtain the compounds in a single step of synthesis from the chalcones. The products precipitated pure and were isolated by filtration. The yields of such reactions, from 45 to 94%, were promising. The product structures were confirmed by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS) techniques. Their antitumor activities were evaluated in HCT-116 (colon) cell lines by the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test. The half maximal inhibitory concentration (IC50) values obtained for the most active chalcones were between 2.9 and 7.5 and for active quinolinone was 19.3 mg L-1. The antitumor activities results suggest that the class of compounds studied has potential for use in cancer research.

Natural α,β-amyrins were isolated from endemic Brazilian Esenbeckia grandiflora Mart., and eight synthetic derivatives were obtained by esterification reactions with bromo acetate, followed by amine treatment. The structures of the all compounds were confirmed by 1H and 13C nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) and high-resolution mass spectrometry (HRMS) data analysis. The derivatives were screened for cytotoxic activity against human tumor cell-lines PC3 (prostate carcinoma), HCT-116 (colon carcinoma) and HL60 (leukemia). HCT-116 and PC3 cell-lines showed weak tumor growth inhibition (range of 13.9-25.4 and 10.3-28.8%, respectively), but the derivatives presented moderate activity against HL60 (range of 13.6-59.0%). Diethyl, aniline, morpholine and imidazole moieties presented higher activities (range of 45.9-59.0%).

Four new alkaloids, Brazoides A-D, together with three known compounds squalene, β-sitosterol and lupeol, were isolated from leaves of Justicia gendarussa. These structures were established by spectrometric techniques, mainly high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR), including comparative analysis with literature values. Structural determination of the compounds, Brazoides A-D, was strengthened by molecular modeling and density functional theory (DFT) calculations to predict the NMR data and compare with the experimental NMR values of these natural products. The new compounds were tested against three human cancer cell lines (glioblastoma, prostate and colon), but none exhibited activity.

Four sulfonamide-chalcone derivatives were prepared and their crystal structure were elucidated by single-crystal X-ray diffraction technique. They were synthesized by Claisen-Schmidt condensation reaction between N-(4-acetylphenyl)benzenesulfonamide or N-(4-acetylphenyl)-2,5-dichlorobenzenesulfonamide with benzaldehyde or p-nitrobenzaldehyde. Values of Z' > 1 are found in three compounds as a consequence of conformerism. The chalcone molecular backbones are featured by different levels of planarity in their conformers. Another conformational variability is in its benzenesulfonamide moiety. In the compound came from N-(4-acetylphenyl)benzenesulfonamide and benzaldehyde, there is a rotation of ca. 180° on the bond axis bridging the sulfonamide and chalcone motifs of one conformer if the two others are taken as references. The cytotoxic activity of all compounds synthesized here and of two other related sulfonamide chalcones was also assessed against three cancer cell lines (SF-295, HCT-8 and MDA-MB-435). The para-nitro compounds were the most active ones among all those tested, regardless of substitution pattern in benzenesulfonamide core.

Vários estudos têm mostrado o potencial citotóxico de derivados da nor-β-lapachona contra células tumorais. Considerando a nor-β-lapachona um importante protótipo, uma série inédita de nor-β-lapachonas substituídas em C-3 foi sintetizada através de uma nova metodologia sintética envolvendo intermediário sintético 3-hidróxi-nor-β-lapachona para o acoplamento de alguns nucleófilos contendo núcleos derivados de carboidratos ou 2H-pirazóis. Todos os derivados foram avaliados frente a quatro linhagens de células tumorais. Duas das substâncias apresentaram moderada citotoxicidade, enquanto as demais inibiram fortemente todas as linhagens tumorais testadas.

Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.

Ethyl acetate extracts of cultures grown in liquid Czapek and on solid rice media of the fungal endophyte Fusarium oxysporum SS46 isolated from the medicinal plant Smallanthus sonchifolius (Poepp.) H. Rob., Asteraceae, exhibited considerable cytotoxic activity when tested in vitro against human cancer cells. Chromatographic separation yielded anhydrofusarubin (1) and beauvericin (2) that were identified based on their ¹H and 13C NMR data. Compounds 1 and 2 showed the strongest cytotoxic activity against different cancer cell lines. Compound 2 also showed promising activity against Leishmania braziliensis. Hexanic extract of F. oxysporum SS50 grown on solid rice media also afforded a mixture of compounds that displayed cytotoxic activity against different cancer cell lines. Chemical analysis of the mixture of compounds, investigated by gas chromatography-mass spectrometry (GC-MS), showed that there was a predominance of methyl esters of fatty acids and alkanes.

The phytochemical investigation of the ethanol extract from leaves of Lecythis pisonis Cambess., Lecythidaceae, resulted in the isolation of seven triterpenes: α- and β-amyrin, uvaol and erythrodiol, ursolic and oleanolic acids and 3β-friedelinol, as well as a mixture of sitosterol and stigmasterol steroids and a diterpene (E)-phytol. The structures of these compounds were identified by¹H and 13C NMR spectral analysis and compared with literature data. The mixture of triterpenes ursolic and oleanolic acids isolated from the active ethereal fraction showed moderate cytotoxic activity. This paper describes for the first time the phytochemical and cytotoxic study of Lecythis pisonis' leaves.

Neoplasias encefálicas constituem a segunda causa neurológica de morte. Foi desenvolvido um modelo animal simplificado de tumor cerebral em ratos utilizando a linhagem celular W256 (carcinoma 256 de Walker) para permitir teste de novos tratamentos. Ratos Wistar foram inoculados nos gânglios da base (caudato subfrontal direito) com uma solução celular tumoral, por via estereotáxica. Este modelo demonstrou crescimento tumoral em 95% dos animais inoculados com sucesso, além de mostrar ausência de metástases extracranianas e infecção sistêmica. A mediana de sobrevida dos animais foi de 10 dias. O volume tumoral estimado foi de 17,08±6,7 mm³ no sétimo dia e de 67,25±19,8 mm³ no nono dia após a inoculação. O tempo de duplicação foi estimado em 24,25 h. O crescimento tumoral induziu a caquexia, mas não houve alterações bioquímicas ou hematológicas. Esse modelo permite fácil reprodução e comporta-se como um tumor indiferenciado, mostrando potencial para estudar migração celular tumoral no sistema nervoso central. Dexametasona 3,0 mg/kg/dia reduziu significantemente a sobrevida dos animais inoculados com tumor nesse modelo. Ciclosporina 10 mg/kg/dia não teve efeito na sobrevida, sendo sua administração bem tolerada.

Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker) cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate). This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Cytotoxic activity of eight plant extracts, native from the Mid-West of Brazil comprising Cerrado, Pantanal and semideciduous forest, was evaluated for MDA-MB-435, SF-295, and HCT-8 cancer cell strains. A single 100 µg.mL-1 dose of each extract was employed with 72 h of incubation for all tests. Doxorubicin (1 µg.mL-1) was used as the positive control and the MTT method was used to detect the activity. Cytotoxicity of distinct polarities was observed in thirty extracts (46%), from different parts of the following species: Tabebuia heptaphylla (Vell.) Toledo, Bignoniaceae, Tapirira guianensis Aubl., Anacardiaceae, Myracrodruon urundeuva Allemão, Anacardiaceae, Schinus terebinthifolius Raddi, Anacardiaceae, Gomphrena elegans Mart., Amaranthaceae, Attalea phalerata Mart. ex Spreng., Arecaceae, Eugenia uniflora L., Myrtaceae, and Annona dioica A. St.-Hil., Annonaceae. Extracts of at least two tested cell strains were considered to be highly active since their inhibition rate was over 75%.

Este artigo descreve a caracterização por CLAE-DAD-EM/EM e CLAE-DEC dos perfis de metabólitos secundários de extratos das folhas de Lychnophora ericoides Mart. de diferentes procedências e suas propriedades citotóxicas e antioxidantes. Extratos foliares de populações representando sete diferentes localidades foram avaliados quanto à atividade antioxidante pelo sistema DPPH e à atividade citotóxica em três linhagens tumorais. Os extratos foram eletroquimicamente caracterizados por CLAE-DEC e seus metabólitos secundários majoritários foram identificados por CLAE-DAD-EM e CLAE-DAD-EM/EM. Um metabolismo secundário defensivo amplificado, juntamente com as mais altas bioatividades antioxidantes e citotóxicas, foi encontrado para as plantas coletadas na interface entre dois tipos de vegetação. Estes resultados fornecem apoio adicional para a hipótese de que plantas ocorrendo na interface entre dois ecossistemas podem ser estimuladas a amplificar sua produção e armazenamento de metabólitos secundários defensivos, devido ao maior número de influências ambientais.

This paper reports HPLC-DAD-MS/MS and HPLC-ECD characterisation of secondary metabolite profiles of Lychnophora ericoides Mart. leaf extracts from different provenances and their cytotoxic and antioxidant properties. Leaf extracts from populations representing seven different locations were evaluated for antioxidant activity by the DPPH radical scavenging system and activity towards cellular growth in three tumor cell lines. The extracts were electrochemically analysed by HPLC-ECD and their main secondary metabolites were identified by HPLC-DAD-MS and HPLC-DAD-MS/MS. An amplified defensive secondary chemistry, together with maximal cytotoxic and antioxidant bioactivities, were found for plants collected at the interface between two types of forest. These findings furnish additional support for the hypothesis that plants occurring at the interface between two forests ecosystems might be stimulated to amplify their own production and storage of defensive secondary metabolites due to the greater number of environmental influences.

Novas 2-(R-fenil)amino-3-(2-metilpropenil)-[1,4]-naftoquinonas (R = H, 4-OMe, 4-Ferrocenil, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 e 3-NO2) derivadas do nor-lapachol [2-hidroxi-3-(2-metilpropenil)-1,4-naftoquinona] foram obtidas em bons rendimentos. A estrutura dos compostos foi proposta com base em estudos de difração de raios-X (R = OMe, 2b), dados de RMN de ¹H e 13C e cálculos teóricos utilizando o funcional B3LYP e a base 6-311+G(2d,p). Os potenciais de meia-onda das aminonaftoquinonas e o deslocamento químico do hidrogênio da cadeia 3-propenil dos compostos 2a-k mostraram boa correlação com as constantes de Hammett dos substituintes presentes no anel fenileno. A avaliação da citotoxicidade evidenciou atividade antitumoral promissora para o substrato metóxi-nor-lapachol 1 e o derivado 4-ferrocenil 2c.

Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 and 3-NO2) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), ¹H and 13C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and ¹H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxy-nor-lapachol 1 and the 4-ferrocenyl derivative 2c.

Cálculos teóricos utilizando os funcionais B3LYP e PBE1PBE e as bases 6-31G(d) e 6-311+G(2d,p) para o sistema 3-(2-fenil-hidrazona)-naftaleno-1,2,4-triona, em solução (dmso) e em fase gasosa, evidenciaram, em ambos os casos, a maior estabilidade da forma ceto-hidrazona (rotâmeros Ia e Ib) comparada às formas enol-azo (rotâmeros IIa/IIb, por volta de 14 kcal mol-1) e III (aproximadamente 6 kcal mol-1). A natureza do substituinte no grupo fenil não influenciou a estabilidade relativa dos tautômeros. Estes resultados foram confirmados por dados espectroscópicos dos derivados HL1-HL13, sintetizados a partir da 2-hidroxi-1,4-naftoquinona e arilaminas (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). A avaliação da atividade anticâncer in vitro (contra linhagens de células cancerosas SF-295, HCT-8, MDAMB-435 e HL-60) e bactericida (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia e Pseudomonas aeruginosa) dos compostos HL1-HL13 e dos seus respectivos complexos de cobre(II), [Cu(L1-13)2], foi avaliada. Em geral a atividade bactericida foi baixa, exceto para o derivado HL5 (R = 3-I), mais ativo do que o controle; entretanto, seu complexo não foi ativo. Por outro lado, a complexação levou, em geral, ao aumento da atividade antitumoral dos pré-ligantes. O complexo [Cu(L13)2] (R = 3-NO2) apresentou moderada citotoxicidade contra leucemia humana (HL-60).

DFT calculations using the B3LYP and PBE1PBE functionals with the standard 6-31G(d) and 6-311+G(2d,p) basis sets were carried out for the 3-(2-phenylhydrazone)-naphthalene-1,2,4-trione system in solution (dmso) and in the gas phase, and showed the keto-hydrazone forms (rotamers Ia and Ib) to be more stable than the enol-azo forms (rotamers IIa and IIb, by about 14 kcal mol-1) and III (by approximately 6 kcal mol-1), independently of the nature of the substituent in the phenylene ring. These results were confirmed by spectroscopic data on the derivatives HL1-HL13, obtained from 2-hydroxy-1,4-naphthoquinone and arylamines (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). The in vitro antitumor (against SF-295, HCT-8, MDAMB-435 and HL-60 cancer cell lines) and antibacterial activities (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa) of compounds HL1-HL13 and of their respective copper(II) complexes, [Cu(L1-13)2], were tested. In general, these compounds exhibited low antibacterial activity, except for HL5 (R = 3-I), more active than the control; however, the corresponding complex was inactive. In contrast, increased cytotoxicity was observed upon complexation. Complex [Cu(L13)2] (R = 3-NO2) presented moderate cytotoxicity against human leukemia (HL-60).

Extracts obtained from 57 marine-derived fungal strains were analyzed by HPLC-PDA, TLC and ¹H NMR. The analyses showed that the growth conditions affected the chemical profile of crude extracts. Furthermore, the majority of fungal strains which produced either bioactive of chemically distinctive crude extracts have been isolated from sediments or marine algae. The chemical investigation of the antimycobacterial and cytotoxic crude extract obtained from two strains of the fungus Beauveria felina have yielded cyclodepsipeptides related to destruxins. The present approach constitutes a valuable tool for the selection of fungal strains that produce chemically interesting or biologically active secondary metabolites.

No presente estudo apresentamos resultados da triagem biológica realizada com 349 extratos obtidos de esponjas marinhas, ascídias, briozoários e octocorais do Brasil, em testes contra 16 linhagens de bactérias comuns e resistentes à antibióticos, uma levedura (Candida albicans), Mycobacterium tuberculosis H37Rv, três linhagens de células tumorais MCF-7 (mama), B16 (melanoma murínico) e HCT8 (cólon), e de inibição da enzima adenina fosforribosil transferase de Leishmania tarentolae (L-APRT). Menos de 15% dos extratos de esponja marinhas apresentaram atividade antibacteriana, contra linhagens resistentes ou não a antibióticos. Quase 40% dos extratos de esponjas marinhas apresentaram atividade antimicobacteriana contra Mycobacterium tuberculosis H37Rv. Foi observada citotoxicidade para 18% dos extratos de esponjas marinhas. Finalmente, menos de 3% dos extratos de esponjas apresentaram atividade inibitória da enzima L-APRT. Menos de 10% dos extratos de ascídias apresentaram atividade antibacteriana. Mais de 25% dos extratos de ascídias apresentaram atividade contra M. tuberculosis e as três linhagens de células tumorais. Somente dois extratos obtidos da ascídia Polysyncraton sp. coletada em duas diferentes épocas (1995 e 1997) apresentaram atividade contra L-APRT. Menos de 2% dos extratos de briozoários e octocorais apresentaram atividade antibacteriana, mas uma alta percentagem de extratos destes animais apresentaram atividades citotóxica (11% e 30%, respectivamente) e antimicobacteriana (60%). O extrato de somente uma espécie de briozoário, Bugula sp., apresentou atividade inibitória da enzima L-APRT. A análise taxonômica de algumas espécies de invertebrados que forneceram alguns dos extratos mais ativos, indicou a ocorrência de atividade biológica em espécies pertencentes a grupos taxonômicos que já foram anteriormente investigados do ponto de vista químico. Estes incluem esponjas marinhas pertencentes aos gêneros Aaptos, Aplysina, Callyspongia, Haliclona, Niphates, Cliona, Darwinella, Dysidea, Ircinia, Monanchora e Mycale, ascídias dos gêneros Didemnum, Aplidium, Botrylloides, Clavelina, Polysyncraton e Symplegma, o briozoário Bugula sp. e octocorais dos gêneros Carijoa e Lophogorgia. A subseqüente investigação química de alguns dos extratos ativos levou ao isolamento de vários metabólitos secundários biologicamente ativos. Os resultados obtidos estão de acordo com resultados obtidos em programas de triagem de atividade biológica de extratos brutos de invertebrados marinhos anteriormente reportados, que apresentaram altas percentagens de extratos bioativos oriundos de Porifera, Ascidiacea, Cnidária e Bryozoa.

Herein we present the results of a screening with 349 crude extracts of Brazilian marine sponges, ascidians, bryozoans and octocorals, against 16 strains of susceptible and antibiotic-resistant bacteria, one yeast (Candida albicans), Mycobacterium tuberculosis H37Rv, three cancer cell lines MCF-7 (breast), B16 (murine melanoma ) and HCT8 (colon), and Leishmania tarentolae adenine phosphoribosyl transferase (L-APRT) enzyme. Less than 15% of marine sponge crude extracts displayed antibacterial activity, both against susceptible and antibiotic-resistant bacteria. Up to 40% of marine sponge crude extracts displayed antimycobacterial activity against M. tuberculosis H37Rv. Cytotoxicity was observed for 18% of marine sponge crude extracts. Finally, less than 3% of sponge extracts inhibited L-APRT. Less than 10% of ascidian crude extracts displayed antibacterial activity. More than 25% of ascidian crude extracts were active against M. tuberculosis and the three cancer cell lines. Only two crude extracts from the ascidian Polysyncraton sp. collected in different seasons (1995 and 1997) displayed activity against L-APRT. Less than 2% of bryozoan and octocoral crude extracts presented antibacterial activity, but a high percentage of crude extracts from bryozoan and octororal displayed cytotoxic (11% and 30%, respectively) and antimycobacterial (60%) activities. The extract of only one species of bryozoan, Bugula sp., presented inhibitory activity against L-APRT. Overall, the crude extracts of marine invertebrates herein investigated presented a high level of cytotoxic and antimycobacterial activities, a lower level of antibacterial activity and only a small number of crude extracts inhibited L-APRT. Taxonomic analysis of some of the more potently active crude extracts showed the occurrence of biological activity in taxa that have been previously chemically investigated. These include marine sponges belonging to genera Aaptos, Aplysina, Callyspongia, Haliclona, Niphates, Cliona, Darwinella, Dysidea, Ircinia, Monanchora and Mycale, ascidians of the genera Didemnum, Aplidium, Botrylloides, Clavelina, Polysyncraton and Symplegma, the bryozoan Bugula sp. and octocorals of the genera Carijoa and Lophogorgia. The subsequent chemical investigation of some of the active extracts led to the isolation of several new biologically active secondary metabolites. Our results are in agreement with previous screening programs carried out abroad, that showed a high percentage of bioactive extracts from Porifera, Ascidiacea, Cnidaria and Bryozoa.

No âmbito de uma linha de pesquisa que visa a obtenção de novas substâncias bioativas, a partir de lipídeos fenólicos não-isoprenóides de Anacardium occidentale, descrevemos a síntese e avaliação citotóxica de novas macrolactonas salicílicas, preparadas a partir da mistura de ácidos anacárdicos, principal constituinte do líquido da casca da castanha de caju (LCC) in natura.

In connection with our ongoing investigation in the search for new bioactive compounds using non-isoprenoid phenolic lipids from Anacardium occidentale as starting material, we describe the synthesis and cytotoxicity screening of some novel salicylate macrolactones prepared from anacardic acids, the major constitutents of natural cashew nut-shell liquid (CNSL).