In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha / Atividade antitumoral in vitro de lactonas sesquiterpenicas de Lychnophora

The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae), which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA), against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition) values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50) for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

As lactonas sesquiterpênicas licnofolida e eremantolida C foram isoladas de Lychnophora trichocarpha Spreng. (Asteraceae), espécie vegetal nativa do cerrado brasileiro e popularmente conhecida por arnica brasileira. As lactonas sesquiterpênicas são conhecidas por apresentarem variadas atividades biológicas, incluindo atividade antitumoral. O presente artigo relata a avaliação da atividade antitumoral in vitro de licnofolida e eremantolida C frente a um painel de 52 linhagens de células tumorais, provenientes de tumores humanos referentes a nove principais tipos de câncer. Os testes foram conduzidos no National Cancer Institute, USA (NCI, USA). Licnofolida apresentou atividade significativa frente a 30 linhagens de células tumorais referentes a sete tipos de câncer, com valores de CI100 (concentração que inibe 100% do crescimento celular) entre 0,41 µM e 2,82 µM. Eremantolida C mostrou atividade significativa frente a 30 linhagens de células tumorais referentes a oito tipos de câncer, com valores de CI100 entre 21,40 µM e 53,70 µM. Licnofolida apresentou valores de concentração letal 50% (CL50) para 30 linhagens de células tumorais humanas entre 0,72 e 10,00 µM, enquanto eremantolida C mostrou valores de CL50 para 21 linhagens entre 52,50 e 91,20 µM. Licnofolida apresentou um interessante perfil de atividade antitumoral. A presença na estrutura química da licnofolida de uma α-metileno-γ-lactona, além de dois grupos ésteres α,β-insaturados, podem ser responsáveis pela melhor atividade e maior citotoxicidade desta substância em relação à eremantolida C.

Antinociceptive effect from Ipomoea cairica extract.

Ipomoea cairica L. Sweet (Convolvulaceae) is used in Brazilian folk medicine for the treatment of rheumatism and inflammations. Ipomoea cairica ethanolic extract (100, 300, 1000 and 3000 mg/kg; per os) induced dose-dependent reduction of response in the formalin test inflammatory phase in mice. The same dose range did not modify neurogenic pain in formalin test, tail-flick reflex latency, carrageenan-induced paw edema, and Rota-Rod test motor performance. From the bio-active fraction 3,5-di-O-caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid were obtained. These compounds have been previously reported to have analgesic and antioxidative effects. A possible explanation for the antinociception is that somehow the compounds present in the extract reduced the release of pro-nociceptive mediators unrelated to carrageenan-induced edema, such as histamine. Interestingly, caffeoylquinic acid derivatives have been reported to inhibit histamine release on in vitro models. The isolated caffeoylquinic acids could explain, at least in part, the antinociceptive effect of Ipomoea cairica polar extract.

Biological activity of the aqueous extract of Lychnophora pinaster Mart.

Lyophilized aqueous extract (LAE) from Lychnophora pinaster Mart (Asteraceae) aerial parts was evaluated in the search of possible biological activities. LAE exhibited trypanocidal activity (113.62 mg/mL), but could not inhibit 5-lipoxygenase in vitro (17 percent of inhibition). LAE chemical characterization by HPLC with UV-Diode Array Detector showed the presence of caffeic acid, isochlorogenic acid, vitexin, isovitexin and quercetin, in comparison with authentic samples.

Neutralizing properties of Musa paradisiaca L. (Musaceae) juice on phospholipase A2, myotoxic, hemorrhagic and lethal activities of crotalidae venoms.

The use of plants as medicine has been referred to since ancient peoples, perhaps as early as Neanderthal man. Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. The study of how people of different culture use plants in particular ways has led to the discovery of important new medicines. In this work, we verify the possible activity of Musa paradisiaca L. (Musaceae) against the toxicity of snake venoms. Musa paradisiaca, an important source of food in the world, has also been reported to be popularly used as an anti-venom. Interaction of Musa paradisiaca extract (MsE) with snake venom proteins has been examined in this study. Phospholipase A2 (PLA2), myotoxic and hemorrhagic activities, including lethality in mice, induced by crotalidae venoms were significantly inhibited when different amounts of MsE were mixed with these venoms before assays. On the other hand, mice that received MsE and venoms without previous mixture or by separated routes were not protected against venom toxicity. Partial chemical characterization of MsE showed the presence of polyphenols and tannins and they are known to non-specifically inactivate proteins. We suggest that these compounds can be responsible for the in vitro inhibition of the toxic effects of snake venoms. In conclusion, according to our results, using mice as experimental model, MsE does not show protection against the toxic effects of snake venoms in vivo, but if was very effective when the experiments were done in vitro.

Anti-PLA2 action test of Casearia sylvestris Sw.

Casearia sylvestris (Flacourtiaceae) is a plant which grows in the wild. The crude extract and pure substances from this plant induced partial inhibition of the PLA: (phospholipase A2) activity of snake venoms and some purified toxins. C. sylvestris extract efficiently neutralized the hemorrhagic and myotoxic activities caused by crude venoms and toxins.

Atividade antibacteriana de furanoeliangólidos / Antibacterial activity of furanoeliangolides

As lactonas sesquiterpênicas licnofólido (1) e eremantólido C (2) e alguns derivados: 1 ,2 -epóxieremantólido C (3), 1 β -hidróxi-2,3-diidroeremantólido C (4), 3 - hidróxieremantólido C (5), cloreto de 4,5-diidroeremantólido-5-n-propilamônio (6) e 1 β -hidróxi- 2,3-diidrolicnofólido (7) foram testadas contra as bactérias Enterococus faecalis S48, Bacillus subtilis CECT 397, Staphylococus aureus ATCC 8, Salmonella typhymurium LT2, Escherichia coli U9 e Proteus sp. Os compostos 1, 4, 5 e 7 apresentaram atividade antibacteriana.

Sesquiterpene lactones lychnopholide (1) and eremantholide C (2) and some derivatives: 1 ,2 -epoxyeremantholide C (3), 1 β -hidroxy-2,3-dihydroeremantolide C (4), 3 -hydroxyeremantholide C (5), 5-n- propylamonium- 4,5-dihydroeremantholide C chloride (6) and 1 β -hydroxy-2,3- dihydrolychnopholide (7) were tested against Enterococus faecalis S48, Bacillus subtilis CECT 397, Staphylococus aureus ATCC 8, Salmonella typhymurium LT2, Escherichia coli U9 e Proteus sp. Compounds 1, 4, 5 and 7 showed activity.

Estudo quimico de Zeyheria montana M. (bolsa de pastor)

Do extrato hexânico das raízes de Zeyheria montana M., uma Bignoniácea conhecida como bolsa‑de‑pastor, empregada popularmente contra doenças de pele, foram isolados os seguintes compostos: lapachol, α‑lapachona, desidro‑α‑lapachona, 4‑hidróxi­-α‑lapachona, β‑sitosterol, ácido esteárico e uma mistura de ácidos graxos. Estas substancias foram identificadas por métodos espectrométricos usuais e/ou comparação com amostras autênticas. No cromatograma do extrato etanólico, obtido por CLAE, foram identificados os picos correspondentes às naftoquinonas isoladas e ao ácido esteárico. A ocorrência de naftoquinonas nas raizes de Z. montana e a atividade antimicrobiana comprovada para o lapachol e a α‑lapachona justificam o uso popular desta espécie.

Zeyheria montana M. (Bignoniaceae) is a widespread species in the Cerrado area of Minas Gerais, Brazil, and is popularly known as bolsa‑de‑pastor. In the Brazilian tradicional medicine its roots are used for the treatment of skin diseases. Several species of Bignoniaceae contain naphthoquinones, and lapachol was previously reported in the stem wood of Z. digitalis. This paper describes the isolation of three naphtoquinones from Z. montana stem barks, namely α‑lapachone, dehydro‑α‑lapachone and 4‑hydroxy‑α‑lapachone, besides lapachol, stearic acid and β‑sitosterol. Furthermore, we report the HPLC fingerprint for the species, which allowed the identification of the isolated compounds, except β‑sitosterol. Since the in vitro antimicrobial activity of lapachol and α‑lapachone has been previously described, the presence of these naphthoquinones in the roots of Z. montana corroborates its popular use for the treatment of skin diseases.

Chemical characterization and biological activity of Macfadyena unguis-cati (Bignoniaceae).

Macfadyena unguis-cati (L.) has been widely used in folk medicine as an anti-inflammatory, antimalarial and antivenereal. The purpose of this study was to chemically characterize the main plant components, and to evaluate the biological properties of some of the fractions derived from leaves (MACb) and liana (MACa) of this plant. Chemical characterization allowed the identification of the compounds corymboside, vicenin-2, quercitrin, chlorogenic acid, isochlorogenic acid, lupeol, beta-sitosterol, beta-sitosterylglucoside, allantoin and lapachol. The biological screening of fractions and/or purified substances derived from fractions revealed antitumoral and antitrypanosomal activities in fractions MACa/lapachol and MACb/MACb21, respectively. The anti-lipoxygenase and anti-cyclooxygenase effect seen in fractions MACa and MACb showed a partial correlation with the anti-inflammatory property attributed to this plant.

New sources and antifungal activity of sesquiterpene lactones.

In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones.

Screening in vitro of natural products against blood forms of Trypanosoma cruzi.

Transmission of Chagas disease by blood transfusion is a major health problem in Central and South America. The annual incidence of transfusion-transmitted Chagas disease in Brazil is about 20,000 cases. Crystal violet is the only trypanosomicidal agent available at present, but there are some restrictions on its use. In a search for possible new chemoprophylactic agents, several natural products of different structural types were tested in vitro against infective blood trypomastigotes of Trypanosoma cruzi. Four compounds had high activity at a concentration of 5 x 10(-4) M: the diarylpropanoids (3R)-claussequinone, (R)-4-methoxydalbergione and (S)-4,4'-dimethoxy-dalbergione, and 15-deoxygoyazensolide, a sesquiterpenelactone. Haemoculture and serology of mice inoculated with infected blood treated with these active compounds were negative after 3 and 6 months. The benzoquinone moiety seemed to be important for this activity since lapachol and related naphthoquinones are known to be trypanosomicidal. 15-Deoxygoyazensolide has previously been recognized as a schistosomicide.

In vitro activity of natural and synthetic naphathoquinones against erythrocytic stages of Plasmodium falciparum

In an attempt to identify new antimalarial compounds we studied the blood schizonticide effect of chemically defined natural products which were isolated from plants (Bignoniaceae) or synthesized. Different concentrations of there drugs (up to 20 micronM) were incubated in vitro with blood forms of Plasmodium falciparum for 72 h. A total of 12 drugs of the naphtoquinones group were tested. Eight of them were isolated from plants (NP) and 4 synthesized (S). Three of the drugs (2 NP and one S) were very active and completely inhibited parasite growth at the higher concentrations used (20 micronM); 5 drugs were partially active (3S and 2NP) and 3 (NP) were totally inactive. Lapachol was among the drugs tested. Although it has been considered a potential antimalarial agent, it exhibited very low activity (20% inhibition of schizogony). The antimalarial activity of our naphthoquinones against drug-resistant strains was superior to that of chloroquine and quinine which were as controls. Two of the P. falciparum strains used for the tests were strongly chloroquine resistant. If these naphthoquinones prove to be active in vivo and are of low toxicity, they will be promising candidates for treatment of human malaria particularly since they are easily synthesized

In vitro activity of natural and synthetic naphthoquinones against erythrocytic stages of Plasmodium falciparum.

In an attempt to identify new antimalarial compounds we studied the blood schizonticide effect of chemically defined natural products which were isolated from plants (Bignoniaceae) or synthesized. Different concentrations of these drugs (up to 20 microM) were incubated in vitro with blood forms of Plasmodium falciparum for 72 h. A total of 12 drugs of the naphthoquinones group were tested. Eight of them were isolated from plants (NP) and 4 synthesized (S). Three of the drugs (2 NP and one S) were very active and completely inhibited parasite growth at the higher concentrations used (20 microM); 5 drugs were partially active (3S and 2NP) and 3 (NP) were totally inactive. Lapachol was among the drugs tested. Although it has been considered a potential antimalarial agent, it exhibited very low activity (20% inhibition of schizogony). The antimalarial activity of our naphthoquinones against drug-resistant strains was superior to that of chloroquine and quinine which were used as controls. Two of the P. falciparum strains used for the tests were strongly chloroquine resistant. If these naphthoquinones prove to be active in vivo and are of low toxicity, they will be promising candidates for treatment of human malaria particularly since they are easily synthesized.