Three new dibenzoylmethane derivatives, (E)-3,4-methylenedioxy-2'-methoxy-2'',2''-dimethylpyrano-(5'',6'':3',4')-7-methoxychalcone, 2'-hydroxy-5'(3'''',3''''-dimethylallyl)-8-(α,α-dimethylallyl)-furano-(4'',5'':3'4')-dibenzoylmethane and 2'-O-(3'',3''-dimethylallyl)-8-(α,α-dimethylallyl)-furano-(4'',5'':3'4')-dibenzoylmethane, were isolated from a dichloromethane extract from the root bark of Muellera filipes (Benth.) M.J. Silva & A.M.G. Azevedo, along with two dibenzoylmethane derivatives, 2'-methoxy-8-(α,α-dimethylallyl)-furano-(4'',5'':3',4')-dibenzoylmethane and 2'-hydroxy-8-(α,α-dimethylallyl)-2",2"-dimethylpyrano-(5",6":3',4')-dibenzoylmethane; one flavanone, isolonchocarpin and one flavone, pongaglabrone, which had been previously isolated from other sources. The molecular structures of the new dibenzoylmethane derivatives were determined by analysis of their spectral data (1H and 13C nuclear magnetic resonance (NMR), 2D-NMR, NOE (nuclear Overhauser effect) and HRMS (high resolution mass spectrometry). The known compounds were identified using 1D experiments and comparison with spectral data from the literature. 2'-O-(3'',3''-Dimethylallyl)-8-(α,α-dimethylallyl)-furano-(4'',5'':3'4')-dibenzoylmethane displayed strong activity against the human cancer cell line OVCAR-3 (ovarian), and 2'-methoxy-8-(α,α-dimethylallyl)-furano-(4'',5'':3',4')-dibenzoylmethane showed high selectivity for cell lines NCI-H460 (lung) and UACC-62 (melanoma).

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.

A investigação fitoquímica das folhas de Guatteria friesiana (Annonaceae) levou à obtenção de três novos alcaloides isoquinolínicos, 13-hidroxi-discretinina, 6,6a-desidroguateriopsiscina e 9-desidroxi-1-metoxi-diidroguattouregidina, juntamente com oito alcaloides conhecidos, 13-hidroxi-2,3,9,10-tetrametoxiprotoberberina, guateriopsiscina, lisicamina, liriodenina, aterospermidina, lanuginosina, 7,8-diidro-8-hidroxipalmatina e palmatina. 13-Hidroxi-2,3,9,10-tetrametoxiprotoberberina, obtido somente através de síntese, é relatada pela primeira vez como produto natural. As estruturas dos alcaloides isolados foram elucidadas por extensivas análises de ressonância magnética nuclear (RMN 1D e 2D), espectrometria de massas (MS) e comparação com os dados descritos na literatura. A atividade citotóxica in vitro dos alcaloides majoritários foi avaliada frente a linhagens de células tumorais e não tumorais. Considerando a atividade média, de acordo com os critérios do National Cancer Institute (NCI/EUA), todos os alcaloides avaliados foram inativos. Entretanto, o alcaloide palmatina apresentou efeito citostático para as linhagens MCF-7 (mama) e U251 (glioma) com valores de GI50 abaixo de 20,0 µmol L-1 (10,5 e 16,2 µmol L-1, respectivamente), sugerindo uma ação citotóxica seletiva.

Phytochemical investigation of the leaves of Guatteria friesiana (Annonaceae) afforded three new isoquinoline alkaloids, 13-hydroxy-discretinine, 6,6a-dehydroguatteriopsiscine and 9-dehydroxy-1-methoxy-dihydroguattouregidine. Eight known alkaloids were also isolated, 13-hydroxy-2,3,9,10-tetramethoxyprotoberberine, guatteriopsiscine, lysicamine, liriodenine, atherospermidine, lanuginosine, 7,8-dihydro-8-hydroxypalmatine and palmatine. 13-Hydroxy-2,3,9,10-tetramethoxyprotoberberine was only obtained by synthesis and is being reported as a natural product for the first time. The structures of the isolated alkaloids were established by extensive analysis of 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometric (MS) data, as well as by comparison with data reported in the literature. The in vitro cytotoxic activity of the major alkaloids was evaluated against tumor and non-tumor cell lines. All of the alkaloids evaluated were determined to be inactive based on National Cancer Institute (NCI/USA) criteria. However, the alkaloid palmatine exhibited a cytostatic effect on MCF-7 (breast) and U251 (glioma) human tumor cell lines, with GI50 values lower than 20.0 µmol L-1 (10.5 and 16.2 µmol L-1, respectively), suggesting a selective cytotoxic action.

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.

O estudo fitoquímico das cascas de Guatteria blepharophylla (Mart.) Mart. forneceu 12 compostos, sendo dois sesquiterpenos, óxido de cariofileno (1) e espatulenol (3), uma xantona, liquexantona (2), uma mistura de esteróides, β-sitosterol (4) e estigmasterol (5), e sete alcalóides isoquinolínicos, O-metilmoschatolina (6), lysicamina (7), nornuciferina (8), liriodenina (9), isocoreximina (10), subsessilina (11) e isomoschatolina (12). Suas estruturas foram determinadas através de métodos espectroscópicos. Os compostos 1-6, 11 e 12 são reportados pela primeira vez nesta espécie. Os dados de RMN 13C (ressonância magnética nuclear) para os compostos 11 e 12 são descritos pela primeira vez na literatura. As atividades antiproliferativa em linhagens de células tumorais humanas e antimicrobiana foram investigadas para os compostos majoritários. O composto 9 mostrou significativa atividade contra linhagens de células de mama (MCF-7, Michigan Cancer Foundation-7), superior ao controle positivo doxorrubicina. O composto 12 apresentou atividade antifúngica similar ao controle positivo nistatina contra Candida albicans

Phytochemical study of the bark of Guatteria blepharophylla (Mart.) Mart. afforded twelve compounds, namely two sesquiterpenes, caryophyllene oxide (1) and spathulenol (3), one xanthone, lichexanthone (2), a mixture of steroids, β-sitosterol (4), and stigmasterol (5), and seven isoquinoline alkaloids, O-methylmoschatoline (6), lysicamine (7), nornuciferine (8), liriodenine (9), isocoreximine (10), subsessiline (11), and isomoschatoline (12). Their structures were established on the basis of spectroscopic methods. Compounds 1-6, 11 and 12 were reported for the first time in this species. The 13C NMR (nuclear magnetic resonance) data for the compounds 11 and 12 are described for the first time in the literature. The antiproliferative activity against human tumour cell lines and antimicrobial activities were investigated for the major compounds. Compound 9 showed significant activity against cell lines of breast (MCF-7, Michigan Cancer Foundation-7), superior to the positive control doxorubicin. Compound 12 presented antifungal activity similar to the positive control nystatin against Candida albicans.

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.

Um grande número de espécies com uso medicinal tradicional ainda continua sem comprovação da eficácia e da segurança de seu uso. Este artigo apresenta uma pequena revisão sobre os trabalhos publicados com boldo (Peumus boldus) e carqueja (Baccharis genistelloides). Os estudos farmacológicos realizados com P. boldus e B. genistelloides comprovam várias das atividades atribuídas popularmente a esses chás, além de correlacionarem esses efeitos a compostos puros, isolados a partir desses extratos. Já os estudos toxicológicos sugerem que o chá de boldo deve ser consumido com moderação e cuidado, principalmente no primeiro trimestre da gravidez (indícios de teratogenia) e no uso por tempo prolongado (indícios de hepatotoxicidade), enquanto o consumo do chá de carqueja deve ser proibido para gestantes (risco comprovado de aborto) e para pacientes que utilizam drogas para tratamento de problemas pressóricos (ação hipotensora). Estes relatos reforçam a necessidade de um maior conhecimento sobre as plantas medicinais utilizadas popularmente, não apenas para a confirmação das atividades descritas pelo uso tradicional, mas também para que o uso seguro seja estabelecido.

There are a great number of medicinal plants without any scientific confirmation about their efficacy and safety. This paper is a short review about two medicinal plants, "boldo do chile" (Peumus boldus) and "carqueja" (Baccharis genistelloides). Pharmacological studies have confirmed several popular indications for P. boldus and B. genistelloides, besides have established a relationship between isolated compounds from these extracts and the pharmacological effects observed. On the other hand, toxicological researches have pointed out that P. boldus tea should not be consumed during a long period (potential hepatotoxicity) and by pregnant, especially during the first three months. Moreover, B. genistelloides tea must be prohibited for pregnant because of confirmed abortive action, and for patients using medicines for blood pressure disorders. These studies point out the continuous necessity of more studies about medicinal plants; only with this knowledge it will be possible a safe and efficient use.

Do extrato hexânico de Eleocharis sellowiana foram isolados o novo triterpeno 3alfa-hidroxi-13alfa,17alfa,21beta-hopano-15,19-diona e hexadecanoato de E-fitila, caracterizados por dados de RMN e EM.

A new triterpene named 3alpha-hydroxy-13alpha,17alpha,21beta-hopan-15,19-dione and E-phytyl hexadecanoate were isolated from the hexanic extract of Eleocharis sellowiana. NMR and MS experiments determined the molecular structures.