The essential oil of roots of Jatropha ribifolia, obtained by hydrodistillation, was characterized in terms of its chemical composition by chromatographic method with flame ionization detection (GC-FID) and gas chromatography coupled to electron ionization mass spectrometry (GC-MS). The analyses and identification pointed by mass fragmentation pattern and retention index revealed the presence of 49 compounds, representing 91.4% of the total oil, with 39.5% of monoterpenes, 43.0% of sesquiterpenes and 8.5% of phenylpropanoids. The major compounds of the oil were β-pinene (9.2%), isoeugenol methyl ether (8.5%), vatirenene (8.4%), α-gurjunene (7.0%), endo-8-hydroxy-cycloisolongifolene (6.6%), α-pinene (6.4%) and p-menth-1-en-8-ol (5.2%). The fractionation by preparative thin layer chromatography (TLC) allowed obtaining five fractions (F1-F5) with different compound contents from the original oil. Some essential oil components showed a significant increase in their levels after fractionation, as borneol (17.9%, F1), 3-thujopsanone (19.1%, F4), isoeugenol methylether (21.2%, F2), 8-oxo-9H-cycloisolongifolene (21.4%, F4), 8-cis-5(1H)-azulenone,2,4,6,7,8,8a-hexahydro-3,8-dimethyl-4-(1-methylethylidene) (23.1%, F4) e endo-8-hydroxy-cycloisolongifolene (38.6%, F2). These fractions and oil were tested in vitro against nine human cancer cell lines by sulforhodamine B assay. The Jatropha oil was more effective in inhibiting the growth of cells NCI-H460 (drug resistant ovarian; GI50 6.2 µg mL–1) and OVCAR-3 (ovarian; GI508.0 µg mL–1). The cancer cells line PC-3 (prostate) was more sensitive to the effects of the fractions showing significant values of GI50 such as for fraction F1, F2 and F4 (< 0.25 µg mL–1). In general the antiproliferative activity of the fractions was more pronounced than that of crude oil.

O estudo fitoquímico das raízes de Dahlstedtia glaziovii (Fabaceae) forneceu um novo dibenzoilmetano (glaziovione), juntamente com dezoito compostos conhecidos. Suas estruturas foram determinadas através de métodos espectroscópicos de ressonância magnética nuclear (NMR) 1D e 2D (correlação heteronuclear única quântica, HSQC, e correlação heteronuclear de múltipla ligação, HMBC) e espectrometria de massas de alta resolução (HRMS). A atividade antiproliferativa foi investigada para os extratos, para os dibenzoilmetanos 2'-metóxi-8-(α-α-dimetilalil)-furano-[4",5":3',4']-dibenzoilmetano, 3,4-metilenodioxi-2'-metóxi-8-(α-α-dimetilalil)-furano-[4",5":3',4']-dibenzoilmetano e pongamol, e para as flavonas lanceolatina B, karanjina, pongapina e 3',4'-metilenodioxi-2",2"-dimetilpirano-[5",6":8,7]-flavona. Os dibenzoilmetanos foram mais ativos do que as flavonas. A atividade antimicrobiana foi investigada para os extratos, sendo que estes não se apresentaram ativos.

A phytochemical study of roots of Dahlstedtia glaziovii (Fabaceae) furnished a new dibenzoylmethane (glaziovione), along with eighteen known compounds. Their structures were determined through 1D and 2D nuclear magnetic resonance (NMR) (heteronuclear single quantum coherence, HSQC, and heteronuclear multiple bond correlation, HMBC) and high-resolution mass spectrometry (HRMS) spectral analyses. The antiproliferative activity was investigated for the crude extracts, the dibenzoylmethanes 2'-methoxy-8-(α-α-dimethylallyl)-furano-[4",5":3',4']-dibenzoylmethane, 3,4-methylenedioxy-2'-methoxy-8-(α-α-dimethylallyl)-furano-[4",5":3',4']-dibenzoylmethane and pongamol, and the flavones lanceolatin B, karanjin, pongapin and 3',4'-methylenedioxy-2",2"-dimethylpyrano-[5",6":8,7]-flavone. The dibenzoylmethanes were more active than the flavones.The extracts were evaluated for their antimicrobial effects, but none was shown to be active.

Natural products are regarded as major and important sources of molecules used in chemotherapy. Hypericum brasiliense Choisy, Hypericaceae, is an annual bush, native in the southern and southeastern Brazil. This species has been used in Brazilian folk medicine the anti-spasmodic and for the treatment of infectious diseases. H. brasiliense is chemically composed by flavonoids and xanthones. In addition, this species contain phloroglucinols, a class of substances with citotoxity effects against tumor cells lines. On the present study, hexanic extract and derivatives phloroglucinols obtained from H. brasiliense were tested against some human tumor cell lines. Hexanic extract presented a potent antiproliferative activity, with selective action on OVCAR-03 (ovarian), NCIADR/ RES (ovarian resistant) and UACC-62 (melanoma) tumor cell lines. Uliginosin B was the most active derivative phloroglucinol, presenting selectivity against NCI-ADR/ RES ( resistant ovarian) and OVCAR-03 (ovarian) tumor cell lines. Analysis of the results suggests that phloroglucinol derivatives with isoprenyl unit closed in the 9' position increases antiproliferative activity. Furthermore, this study contributes to identification of anti-tumor molecules and valorization of Hypericum brasiliense.

The cytotoxicity of a hexanic fraction produced from the ethanolic crude extract, obtained from Jatropha ribifolia (Pohl) Baill, Euphorbiaceae, roots was evaluated against ten human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460,786-O, UACC-62, K-562, U251) compared with doxorrubicine as positive control. Compounds jatrophone and cyperenoic acid were isolated from the hexanic extract and characterized by spectroscopic techniques (NMR of ¹H, 13C and IR). The in vitro antiproliferative activity of jatrophone showed selectivity in a concentration dependent way with Total Inhibition growth of: glioma 0.57 µg mL-1 (U251), breast cancer 9.2 µg mL-1 (MCF-7), adriamycin-resistant ovarian cancer 0.96 µg mL-1 (NCI-ADR/RES), kidney 4.2 µg mL-1 (786-0), prostate cancer 8.4 µg mL-1 (PC-3), colon cancer 16.1 µg mL-1 (HT29) and leukemia 0.21 µg mL-1 (K-562).

As sementes de Pterodon pubescens Benth. (Pp), disponíveis comercialmente no Brasil, são utilizadas na medicina popular em preparações anti-inflamatórias, analgésicas e anti-reumáticas. O presente estudo demonstrou as propriedades antinociceptivas da mistura de isômeros 6α-hidroxi-7β-acetoxi-vouacapano-17β-oato de metila e 6α-acetoxi-7β-hidroxi-vouacapano-17β-oato de metila (C1) isolada de Pp, empregando modelos experimentais diferentes. Um estudo de estabilidade foi realizado para investigar a relação da microencapsulação por "spray-drying" na manutenção do efeito antinociceptivo. Para isso, amostras de C1 e extrato de Pp foram monitorados no estudo de estabilidade acelerada, avaliando tanto amostras microencapsuladas como não microencapsuladas. Foi observado que a amostra C1 possui atividade antinociceptiva, revelada pelos ensaios das contorções abdominais e de formalina; foi observada também atividade significativa antialodínica, mas não efeito anti-hiperalgésico. A microencapsulação manteve a atividade e integridade de C1 e do extrato bruto de Pp, demonstrando que a microencapsulação por "spray drying" é uma alternativa útil para aumentar o tempo de prateleira.

Pterodon pubescens Benth. (Pp) seeds, commercially available in Brazil, are used in folk medicine in anti-inflammatory, analgesic, and anti-rheumatic preparations. The present study demonstrated the antinociceptive properties of isomers 6α-hydroxy-7β-acetoxy-vouacapan-17β-oate methyl ester and 6α-acetoxy-7β-hydroxy-vouacapan-17β-oate methyl ester (C1), isolated from (Pp), employing different experimental models. A stability study was performed to investigate the relationship of microencapsulation by spray-drying on the maintenance of antinociceptive action. Therefore, C1 and Pp extract samples were monitored in accelerated stability study, evaluating both microencapsulated and non-microencapsulated samples. It was observed that sample C1 possess antinociceptive activity revealed by writhing and formalin tests; C1 showed significantly anti-allodynic, but not antihyperalgesic effect; the microencapsulation maintained the activity and integrity of both, sample C1 and Pp crude extract; microencapsulation by spray drying is a useful alternative to increase shelf life.

A investigação fitoquímica dos frutos maduros de Solanum caavurana Vell. (Solanaceae) forneceu um novo alcaloide esteroidal do tipo espirosolano, caavuranamida, juntamente com os alcaloides 4-tomatiden-3-ona e 5α-tomatidan-3-ona. Suas estruturas foram elucidadas através de métodos espectroscópicos. As atividades antiproliferativa e antimicrobiana para o extrato etanólico e subfrações provenientes de partição e de extração ácido-base foram investigadas. A caavuranamida apresentou atividade antibacteriana similar ao controle positivo cloranfenicol contra Rhodococcus equi.

Phytochemical investigation of the ripe fruits of Solanum caavurana Vell. (Solanaceae) afforded a novel steroidal alkaloid with spirosolane-type skeleton, named as caavuranamide, together with the alkaloids 4-tomatiden-3-one and 5α-tomatidan-3-one. Their structures were elucidated on the basis of spectroscopic methods. The antiproliferative and antimicrobial activities for the ethanolic extract, sub-fractions obtained from partition and acid-base treatment were also evaluated. Caavuranamide showed antibacterial activity similar to the chloramphenicol positive control against Rhodococcus equi.

Croton macrobothrys Baill, Euphorbiaceae, is a tree from the Atlantic Forest in Southern Brazil, used in traditional medicine and popularly known as "dragon's blood" and "pau-sangue". Leaf n-hexane, dichloromethane and methanol extracts were analyzed by GC/MS and evaluated for their in vitro antiproliferative activity on cell lines 786-0 (kidney), HT-29 (colon), K562 (leukemia), NCI-ADR/RES (drug resistant ovary), NCI-H460 (lung), MCF-7 (mammary), PC-3 (prostate), OVCAR-3 (ovary), U251 (glioma) and UACC-62 (melanoma). The dicloromethane extract exhibited activity against all cell lines at the concentration 25 µg/mL, in particular on cell lines NCI-H460 (GI50 0.33 μg/mL) and K5662 (GI50 0.91 μg/mL). Relevant constituents in dichloromethane extract are the alkaloids corydine and salutaridine, as well as the diterpenes geranylgeraniol and crotonin-derived clerodanes.

Com o propósito de aumentar a atividade anticâncer demonstrada anteriormente pelas 1-fenilssubstituído-3-(2-tioxo-1,3,4-oxadiazol-5-il) β-carbolinas 1a-c, neste trabalho foram realizadas a síntese e a avaliação in vitro da atividade antitumoral de novas bases de Mannich 2-7(a-c), derivadas da introdução de diferentes grupos alquilamino(metil) na unidade 1,3,4-oxadiazol de 1a-c. Os derivados 1a-c e 2-7(a-c) foram também avaliados quanto às atividades antibacteriana e antifúngica. Adicionalmente, um estudo in silico das propriedades de ADME dos novos compostos sintetizados 2-7(a-c) foi realizado pela avaliação de seus parâmetros de Lipinski e de dados de área de superfície topológica polar (TPSA) e de porcentagem de absorção (% ABS).

With the purpose of activity enhancement of 1-substituted phenyl-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carbolines 1a-c, reported as potential antitumor agents in our previous study, herein we report the synthesis and antitumor activity evaluation of several novel Mannich bases 2-7(a-c), by the introduction of different alkylamino(methyl) groups in the 1,3,4-oxadiazole unity of 1a-c. The antimicrobial activities of 1a-c and of 2-7(a-c) were also evaluated. Additionally, an in silico study of the ADME properties of novel synthesized β-carboline derivatives 2-7(a-c) was performed by evaluation of their Lipinski's parameters and topological polar surface area (TPSA) and percentage of absorption (% ABS) data.

O fracionamento biomonitorado do extrato diclorometânico das sementes de Pterodon pubescens Benth forneceu o 6α-acetóxi-7β-hidróxi-vouacapano 1 (inédito), além de quatro diterpenos furânicos (2, 3, 4 e 5). A atividade antiproliferativa dos compostos foi avaliada in vitro contra as linhagens de células tumorais humanas UACC-62 (melanoma), MCF-7 (mama), NCI-H460 (pulmão), OVCAR-03 (ovário), PC-3 (próstata), HT-29 (colon), 786-0 (rim), K562 (leucemia) e NCI-ADR/RES (ovário com fenótipo de resistência a múltiplos fármacos). Os resultados foram expressos em três concentrações efetivas GI50 (concentração para que ocorra 50% de inibição de crescimento), TGI (concentração que resulta em inibição total de crescimento) e LC50 (concentração que resulta em 50% de morte celular). A citotoxicidade in vitro foi avaliada também frente a uma linhagem de célula murina normal (3T3). Este é o primeiro relato de atividade anticâncer para os compostos 1, 4 e 5, que apresentaram grande seletividade, dependente da concentração, para PC-3. O composto 1 foi 26 vezes mais potente para inibir 50% do crescimento (GI50) de PC-3, 15 vezes mais citostático (TGI) e 6 vezes menos tóxico (LC50) quando comparado com Doxorrubicina (controle).

Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC50 (concentration that produces -50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic.

No presente trabalho descrevemos a síntese e a avaliação da atividade antiproliferativa, frente a linhagens de células tumorais humanas, de derivados do R-(+)-limoneno (3-18) contendo uma unidade tiouréia substituída. Os derivados com substituintes arílicos (3-6) exibiram atividade citostática frente a todas linhagens testadas, com inibição de 50% do crescimento celular (GI50) em concentrações na faixa de 2,5 a 24 µmol L-1. Os compostos 3, 10, 12 e 16 foram os mais ativos, com GI50 na faixa de 0,41 a 3,0 mmol L-1, frente a diferentes linhagens celulares.

A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytotastic activity in the full panel of cell lines tested, with GI50 values in the range of 2.5 to 24 µmol L-1. Compounds 3, 10, 12 and 16 were the most active with GI50 values in the range of 0.41 to 3.0 µmol L-1, against different cell lines.