Effect of the metanolic extract from the leaves of Garcinia humilis Vahl (Clusiaceae) on acute inflammation.

Garcinia humilis is popularly used to treat digestive, intestinal and inflammatory illness. We investigated the in vivo and in vitro effects of the methanol extract of G. humilis leaves (MEGh) on inflammatory cells behavior (migration and chemical mediators release) and hypersensitivity. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice treated orally with MEGh (0.1-30 mg/kg). Leucocyte migration, chemical mediators secretion (TNF, IL-1ß, IL-6 and CXCL1) and protein exudation were quantified in the exudate. The adhesion molecules expression (CD62L and CD18), chemical mediators and chemotaxis was evaluated using neutrophils or macrophages RAW.264.7 previously treated with the extract (1-100 µg/mL) and activated with LPS. The anti-inflammatory activity of the isolated compounds friedelin, canophyllol, amentoflavone and 3-desmethyl-2-geranyl-4-prenylbellidypholine xanthone (10 µM) was evaluated in macrophages nitric oxide (NO) and TNF release. MEGh, given orally (30 mg/kg), significantly reduced neutrophil migration and decreased TNF, IL-1ß and CXCL1 levels, without interfering with protein exudation and IL-6. In vitro, the extract significantly reduced IL-1ß and IL-6 levels but did not alter TNF and CXCL1. The MEGh also reduced the expression of CD62L and CD18 and consequently neutrophil chemotaxis. The compounds friedelin, amentoflavone and 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone decreased the secretion of NO and TNF by RAW264.7. The MEGh effects were extended to the pain-like behaviour induced by carrageenan in the mice hindpaw. MEGh presented important anti-inflammatory effects probably due to its activity on neutrophil migration and on important chemical mediator release, scientifically reinforcing its use as medicinal plant.

Structural Elucidation and Antimicrobial Characterization of Novel Diterpenoids from Fabiana densa var. ramulosa.

Novel diterpenoids were isolated from the extracts of Fabiana densa var. ramulosa and found to display a selective activity against Gram-positive bacterial strains with negligible cytotoxicity toward human keratinocytes. This study highlighted the role played by the acidic group at C18 of the tetracyclic ent-beyerene scaffold for antibacterial effects and how the length and flexibility of the alkyl chain between the two carbonyl groups are crucial factors to increase the antimicrobial activity of the molecules, supporting the development of natural products from F. densa and their derivatives for treatment of microbial infections.

The validation of Calophyllum brasiliense ("guanandi") uses in Brazilian traditional medicine as analgesic by in vivo antinociceptive evaluation and its chemical analysis.

Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test. The amount of 1,2-dimethoxyxanthone was determined in the fraction by UPLC-DAD. CFCB inhibited abdominal constrictions induced by acetic acid up to 97%, with an ID50 of 9.4 mg/kg (i.p.) and 131.8 mg/kg (p.o.). In the formalin test, CFCB impaired paw licking with an ID50 of 26.3 mg/kg for the first phase and 27.5 mg/kg for the second phase (i.p.). The painful response evoked by capsaicin and glutamate was significantly reduced (ID50 26.7 and 47.9 mg/kg, i.p.). The latency time was increased up to 76% at 60 mg/kg (i.p.) in the hot-plate test. 1,2-Dimethoxyxanthone was almost three times more potent (ID50 27.6 µmol/kg, i.p.) than brasiliensic acid (72.0 µmol/kg) in acetic acid-induced writhing test. The amount of the xanthone was estimated as 92.5 mg/g in the extract. CFCB inhibited the nociceptive response associated to several agents. TRPV1 channels play an important role in the mechanism of action of the fraction. In addition, 1,2-dimethoxyxanthone largely contributes to the antinociceptive effect of CFCB.

Diuretic, natriuretic and potassium-sparing effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats.

Active constituents from natural origin have long been used for the treatment of patients suffering from cardiovascular and renal diseases. This study therefore aimed to investigate the diuretic and natriuretic properties of nothofagin, a dihydrochalcone isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats. Male Wistar normotensive rats were orally treated with vehicle (1 ml/kg); hydrochlorothiazide (HCTZ; 25 mg/kg); ethyl acetate fraction from L. dasytricha (EALD; 3-30 mg/kg) and nothofagin (NOT; 0.3-3 mg/kg). Spontaneously hypertensive rats (SHR) received NOT (1 mg/kg), HCTZ (25 mg/kg) or vehicle. The cumulative diuretic index, urinary electrolytes excretion (Na+ and K+), pH, density and conductivity were measured at the end of the experiment (after 8 h). A7r5 and L929 cell lines were used to measure cell viability after exposure to NOT. Nitric oxide generation was quantified in A7r5 cell supernatant, and DPPH assay was used for evaluating the antioxidant properties of NOT. The urinary volume of normotensive rats were increased after the treatment with EALD, without any changes in Na+ or K+ excretion. NOT was able to induce diuresis and natriuresis, but not kaliuresis, in both normotensive and hypertensive rats. The reduction in prostanoids generation through cyclooxygenase inhibition, as well as the muscarinic receptor antagonism, fully avoided NOT-induced increases in diuretic index. NOT, which did not interfere with L929 or A7r5 cell viability, was able to stimulate nitric oxide generation in A7r5 cell, besides showing an antioxidant effect in scavenging the free-radical DPPH. Taken together, our study shows, for the first time, the diuretic, natriuretic and potassium-sparing effect of nothofagin in rats, which was associated with prostanoids generation, muscarinic receptor activation and antioxidant properties.

Gastroprotective xanthones isolated from Garcinia achachairu: Study on mucosal defensive factors and H(+), K(+)-ATPase activity.

The present study was designed to investigate the gastroprotective effect of xanthones 7-preniljacareubin (PJB), 1,3,5,6-tetrahydroxy xanthone (THX), 3-demethyl-2-geranyl-4-prenylbellidypholine (DGP) and 1,5,8-trihydroxy-4', 5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) isolated of branches from G. achachairu. Their structures were identified through the spectroscopic analysis in comparison with previously reported data. The xanthones were tested at dose of 10 mg/kg against ethanol 60%/HCl 0.3 N-induced gastric ulcer in female swiss mice. The xanthones PJB, THX, DGP and TDP exhibit gastroprotective effect after intraperitoneal treatment, but only the first two displayed anti-ulcer activity after oral administration. Both PJB and THX augmented the antioxidative capacity of tissue by an increase in glutathione levels, as well as were able to prevent an increase in myeloperoxidase activity and tumor necrosis factor level. On the other hand, only THX showed an in vitro free radical scavenger activity, and only PJB avoided mucus depletion on gastric mucosa, which was not associated with an increase in mucin production at glandular level. In addition, PJB and THX inhibited the in vitro H(+)K(+)-ATPase activity at similar range as omeprazole. Together, these results demonstrate the anti-ulcer efficacy of xanthones isolated from G. achachairu, which can contribute for future directions in the development of effective strategies to improve gastric diseases.

Chrysophyllum cainito leaves are effective against pre-clinical chronic pain models: Analysis of crude extract, fraction and isolated compounds in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysophyllum cainito L. (Sapotaceae), commonly known as caimito or star apple, is a neotropical tree valued for its ornamental quality and edible fruits. Besides its culinary use, the leaves are also popularly used to treat diabetes mellitus and several inflammatory diseases. AIM OF THIS STUDY: This study aimed to complement previous data obtained about the anti-hypersensitivity effects of the crude methanol extract (CME), CHCl3 fraction and isolated compounds obtained from C. cainito. MATERIALS AND METHODS: The CME, CHCl3 fraction and two isolated triterpenes identified as 3ß-Lup-20(29)-en-3-yl acetate (1) and Lup-20(29)-en-3ß-O-hexanoate (2) were evaluated regarding their effects using clinical pain models, such as post-operative, inflammatory and neuropathic pain. Acute inflammatory pain models induced by PGE2, epinephrine, LPS and CFA were also used to improve the knowledge about the mechanism of action. RESULTS: The animals treated with the CME and submitted to PGE2, epinephrine, LPS or CFA had the mechanical hypersensitivity significantly reduced. When repeatedly administered, the CME enhanced the mechanical withdrawal threshold of mice submitted to post-operative pain model, CFA-induced chronic inflammatory pain and two different models of neuropathic pain. In turn, the CHCl3 fraction presented anti-hypersensitivity effect against epinephrine- or LPS-induced hypersensitivity, with a more prominent activity in both the neuropathic pain models. The compound 1 seems to present the same profile of the CHCl3, whereas compound 2 exhibited activity similar to the CME. CONCLUSIONS: This data suggests that the CME effect involves interference in the production, release or action of some chemical mediators, such as PGE2, sympathetic amines, cytokines, etc. Part of these effects was observed with the CHCl3 fraction, emphasizing the prominent inhibition of neuropathic pain. The results also demonstrated that part of the CME effects are due to the presence of the triterpenes 1 and 2, but it is important to mention that we cannot discard the effects of countless other compounds presented in the crude extract, acting in a synergic way.

Antiproliferative effect of extracts and pyranonaphthoquinones obtained from Cipura paludosa bulbs.

CONTEXT: Cipura paludosa Aubl. (Iridaceae) is widely used in folk medicine to treat several ailments. Experimental studies have confirmed its anti-inflammatory, antinociceptive, and neuroprotective effects. OBJECTIVE: This study evaluates the possible antiproliferative potential of the crude methanol extract and three isolated compounds from the bulbs of C. paludosa. MATERIALS AND METHODS: Phytochemical analysis was carried out by conventional chromatographic techniques, and the resulting compounds were identified by NMR (1)H and (13)C. The antiproliferative activity was analysed using the sulforhodamine B assay. RESULTS: Crude methanol extract of C. paludosa bulbs showed GI50 values of between 1.6 and 30.8 µg/mL. The naphthoquinone derivatives (eleutherine, isoeleutherine, and eleutherol) isolated from the bulbs of C. paludosa exhibited promising cytotoxicity against several human tumour cell lines, especially the two main compounds, eleutherine and isoeleutherine, against glioma and breast cancer cell lines, with TGI values of between 2.6 and 13.8 µg/mL. CONCLUSION: Cipura paludosa bulbs produce active principles with relevant antiproliferative potential, such as naphthoquinone derivatives, identified as eleutherine, isoeleutherine, and eleutherol. This is the first report indicating C. paludosa with antiproliferative potential.

In vitro antiproliferative activity of uncommon xanthones from branches of Garcinia achachairu.

Context Garcinia achachairu Rusby (Clusiaceae) popularly known as 'achachairu' is used in folk medicine to treat rheumatism, inflammation, pain and gastric disorder. Objective The present study investigated the chemical profile and antiproliferative effects of the methanolic extract, fractions and two xanthones, against some carcinoma cell lines in vitro. Materials and methods The compounds were isolated and identified by chromatographic and spectroscopic methods. The extract, fractions and compounds were tested human tumour cell lines of U-251 (glioma), MCF-7 (breast), NCI/ADR-RES (ovary expressing multi-drug resistance phenotype), 786-0 (kidney), NCI-H460 (lung, non-small cells), PC-3 (prostate) and HT-29 (colon), non-tumour cell line HaCat (human keratinocytes) in doses of 0.25-250 µg mL (-) (1) for 48 h. The antiproliferative activity was determined by spectrophotometric quantification (at 540 nm) of the cellular protein content using sulphorhodamine B assay. The prediction of parameters involved in the molecular bioavailability was executed directly by ChemDoodle (version 5.0.1) software (iChemLabs, LLC, Somerset, NJ). Results 3-Demethyl-2-geranyl-4-prenylbellidypholine (1) and 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (2), gartanin (3) and stigmasterol (4) were identified on the basis of spectroscopic techniques. Compounds 1 and 2 exhibited cytocidal activity, especially against breast, prostate and kidney cell lines, with TGI values of 15.8, 4.9, 9.1 and 39.4, 44.7, 40.9 µg/mL, respectively. Discussion and conclusion The presence of two sets of hydrophobic and hydrophilic groups in separate domains in each molecule might play a role in the mediation of tumour-specific action. Our data show that G. achachairu have potent antiproliferative action and should be considered an important source of potent anticancer compounds.

A new indole-alkaloid and a new phenolic-glycoside with cytotoxic activity from Strychnos fendleri.

A new indole alkaloid strychnosinol (1) and a new phenolic-glycoside (2) were isolated from the bark and leaves of Strychnos fendleri Sprague & Sandwith, together with six known compounds reported for the first time in this species. The structures of these compounds were determined on the basis of spectroscopic data; mainly those obtained by using (1)H and (13)C NMR (1D and 2D) and mass spectrometry. Strychnosinol (1) and the phenolic glycoside (2) together with compounds 3-8 were evaluated for cytotoxicity against a panel of five tumour cell lines; IC50 values between 0.090 and 0.227 µM for the human tumour cell lines were observed for compound 2.

Macrocarpal-like Compounds from Eugenia umbelliflora Fruits and Their Antibacterial Activity.

Certain members of the genus Eugenia are used as foods. One of these species is Eugenia umbelliflora, which is used for its fruits. The aim of the study was to isolate the constituents of the CH2Cl2 fraction obtained from E. umbelliflora O. Berg (Myrtaceae) and also to evaluate its antimicrobial properties. Two new meroterpenoids, eugenial C (3) and eugenial D (4) were isolated from the unripe fruits of E. umbelliflora and their structures established mainly by extensive NMR spectroscopy. In previous studies, the CH2Cl2 extract showed significant antibacterial activity, which can be attributed to meroterpenoids isolated in this study. The compounds eugenials C and D exhibited potent activity against Bacillus subtilis and Staphylococcus aureus and different strains of MRSA and activity similar to those of the antibiotics used in antimicrobial therapies.

Uncommon Trimethoxylated Flavonol Obtained from Rubus rosaefolius Leaves and Its Antiproliferative Activity.

This study shows the evaluation the antiproliferative effect of the extract, fractions, and uncommon compounds isolated from R. rosaefolius leaves. The compounds were identified by conventional spectroscopic methods such as NMR-H(1) and C(13) and identified as 5,7-dihydroxy-6,8,4'-trimethoxyflavonol (1), 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (2), and tormentic acid (3). Both hexane and dichloromethane fractions showed selectivity for multidrug-resistant ovary cancer cell line (NCI-ADR/RES) with total growth inhibition values of 11.1 and 12.6 µg/ml, respectively. Compound 1 also showed selective activity against the same cell line (18.8 µg/ml); however, it was especially effective against glioma cells (2.8 µg/ml), suggesting that this compound may be involved with the in vitro antiproliferative action.

Seasonal phytochemical study and antimicrobial potential of Vetiveria zizanioides roots.

This paper describes the seasonal phytochemical variation and the antimicrobial potential of V. zizanioides roots collected in Brazil. Considering the high levels of chemical constituents and their biological activity in dichloromethane fraction, the plants were grown in different seasons and the respective dichloromethane fractions were analyzed by gas chromatography-mass spectrometry. The antimicrobial activity was evaluated against several pathogenic microorganisms by determining the minimum inhibitory concentration (MIC) using the agar dilution method. Yields of dichloromethane fractions from plants collected in the autumn and spring occurred in a higher proportion than in other seasons. Khusimol (2) was isolated by column chromatography and identified by NMR and CG-MS, along with other sesquiterpenes, including ß-vetivenene (1), vetiselinenol (3), isovalencenol (4), vetivenic acid (5), α-vetivone (6) and ß-vetivone (7). Some extracts showed promising antimicrobial effects, with MICs ranging from 31.25 to 500 µg mL-1. Kushimol was slightly active against the tested microorganisms.

Chemical composition, antioxidant and antinociceptive properties of Litchi chinensis leaves.

OBJECTIVES: Litchi chinensis has been traditionally used in folk medicine to treat several ailments. In this study, we investigated the chemical composition, antioxidant and antinociceptive activity of L. chinensis leaves. METHODS: The antioxidant capacity of the extract, fraction and compounds was evaluated using the 1,1-diphenyl-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, and the liposome model with peroxyl radicals generated by 2,2'-azobis (2-amidinopropane) dihydrochloride radical. The pharmacological models of acute nociception used in mice were: writhing test with acetic acid (AA), hotplate (HP), glutamate (GLU), capsaicin (CP) and formalin (FM) tests. KEY FINDINGS: The main compounds isolated were procyanidin A2 (PA2), procyanidin B2 (PB2) and (-)-epicatechin. The biochemical features of the crude extracts and their ethyl acetate fraction (EtOAcFR) presented high antioxidant activity, and the antioxidant activity of PA2 and PB2 was remarkably high, with DPPH and ABTS. The crude methanol extract (MeOHEXTR), EtOAcFR and PB2 were effective in reducing nociception in FM and HP models. MeOHEXTR and EtOAcFR treatments also reduced pain induced by GLU and AA. In the CP model, only EtOAcFR and PB2 were effective. CONCLUSIONS: The results demonstrate the antinociceptive and antioxidant of MeOHEXTR, EtOAcFR and PB2.

Discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB) inhibitors from natural products.

Protein tyrosine phosphatase B (PtpB) is one of the virulence factors secreted into the host cell by Mycobacterium tuberculosis. PtpB attenuates host immune defenses by interfering with signal transduction pathways in macrophages and, therefore, it is considered a promising target for the development of novel anti-tuberculosis drugs. Here we report the discovery of natural compound inhibitors of PtpB among an in house library of more than 800 natural substances by means of a multidisciplinary approach, mixing in silico screening with enzymatic and kinetics studies and MS assays. Six natural compounds proved to inhibit PtpB at low micromolar concentrations (< 30 µM) with Kuwanol E being the most potent with K i = 1.6 ± 0.1 µM. To the best of our knowledge, Kuwanol E is the most potent natural compound PtpB inhibitor reported so far, as well as it is the first non-peptidic PtpB inhibitor discovered from natural sources. Compounds herein identified may inspire the design of novel specific PtpB inhibitors.

Drimanes from Drimys brasiliensis with leishmanicidal and antimalarial activity.

This paper evaluates CHCl3 and CH3OH extracts of the stem bark, branches and leaves of Drimys brasiliensis and drimane sesquiterpenes isolated from the stem bark against strains of Leishmania amazonensis and Leishmania braziliensis promastigotes and Plasmodium falciparum trophozoites. All of the extracts and compounds were tested in cell lines in comparison with reference standards and cell viability was determined by the XTT method. The CHCl3 and CH3OH extracts from the stem bark and branches yielded promising results against two strains of Leishmania, with 50% inhibitory concentrations (IC50 ) values ranging from 39-100 µg/mL. The CHCl3 extract of the stem bark returned IC50 values of 39 and 40.6 µg/mL for L. amazonensis and L. braziliensis, respectively. The drimanes were relatively effective: 1-ß-(p-coumaroyloxy)-polygodial produced IC50 values of 5.55 and 2.52 µM for L. amazonensis and L. braziliensis, respectively, compared with 1-ß-(p-methoxycinnamoyl)-polygodial, which produced respective IC50 values of 15.85 and 17.80 µM. The CHCl3 extract demonstrated activity (IC50 of 3.0 µg/mL) against P. falciparum. The IC50 values of 1-ß-(p-cumaroyloxyl)-polygodial and 1-ß-(p-methoxycinnamoyl)-polygodial were 1.01 and 4.87 µM, respectively, for the trophozoite strain. Therefore, the results suggest that D. brasiliensis is a promising plant from which to obtain new and effective antiparasitic agents.

Antimicrobial activity of extracts and fractions from aerial parts of selected plants (Garcinia achachairu, Macrosiphonia velame, Rubus niveus and Pilea microphylla) against some pathogenic microorganisms.

As part of the program of our research group to search for new and effective substances from the Brazilian biodiversity, the present work evaluates the antibacterial activity of four species from the Brazilian flora (Garcinia achachairu, Macrosiphonia velame, Rubus niveus and Pilea microphylla) against Bacillus subtilis, Staphylococcus aureus and S. saprophyticus (Gram-positive bacteria), Escherichia coli (Gram-negative bacterium) and Candida albicans (yeast). The extracts of R. niveus and M. velame showed promising antibacterial activity with MICs, ranging from 1000 to 125 microg/mL. Bio-guided fractionation of M. velame yielded four compounds, with the highest inhibition being observed for compound 3, with a MIC of 125 microg/mL against S. aureus. The combinations of fractions 2 and 4 showed beneficial effect against Gram-positive bacteria (additive effect), suggesting a possible synergistic effect.

Gastroprotective effects of extracts and guttiferone A isolated from Garcinia achachairu Rusby (Clusiaceae) against experimentally induced gastric lesions in mice.

This study was undertaken to evaluate the gastroprotective properties of seed, leaf, and branch methanolic extracts and guttiferone A obtained from Garcinia achachairu (Clusiaceae). Mice were used in all the models, and treatments were administered orally only in pylorus-ligated model of the extracts, and drugs were administered intraduodenally. Treatment with different extracts (500 mg/kg) significantly reduced the ulcerative lesions in the ethanol/HCl-induced model; however, the seed extract was most active. When tested in different doses (50, 250, or 500 mg/kg), the seed extract of G. achaicharu showed a dose-dependent effect with a percentage of inhibition of gastric lesions of 41, 49, and 85 %, respectively. The seed extract also significantly reduced the ulcerative lesions in the indomethacin/bethanechol-induced ulcer. In this model, the percentage of inhibition of ulcer was 24, 58, and 90 %, respectively. Regarding the model of gastric secretion, a reduction of gastric juice volume and total acidity was observed, as well as an increase in gastric pH. Considering that the seed extract was the most active, it was subjected to silica gel column chromatography, leading to the isolation of guttiferone A. The isolated compound and omeprazole were evaluated in the HCl/ethanol-induced ulcer model. In this assay, both compounds at a dose of 30 mg/kg reduced the ulcerative lesions by about 75 %. These results demonstrate, for the first time, that extracts obtained from G. achachairu and guttiferone A produce gastroprotective effects, corroborating ethnomedicinal use of this plant.

Phytochemical analysis and antinociceptive properties of the seeds of Garcinia achachairu.

In a search for new and effective analgesic substances from the Brazilian biodiversity, the present study evaluates the chemical composition and antinociceptive potential of the methanol extract and a pure compound obtained from the seeds of Garcinia achachairu Rusby (Clusiaceae). The methanolic seed extract was directly subjected to purification by column chromatography and the purification was monitored by thin-layer chromatography. The main isolated compound was identified as Guttiferone A by comparison of conventional spectroscopic data (IR, NMR-(1)H and (13)C) to the literature data which was isolated for the first time from this plant. When evaluated in the acetic acid-induced nociception model in mice, the methanolic seed extract had an ID(50) (Inhibitory dose) of 13.1 (11.23-14.91) mg/kg and a maximal inhibition of 72 ± 4%. In the same model, Guttiferone A had an ID(50) of 4.54 (3.29-6.24) mg/kg and a maximal inhibition of 73 ± 5%. The methanolic seed extract and Guttiferone A were also active in pain models induced by formalin, capsaicin, glutamate and carrageenan. These data suggest that the antinociceptive effect of Guttiferone A partly depends on its interference with the synthesis or activity of the cytokine TNF-α, the keratinocyte-derived chemokine KC, and/or PGE(2). These data support, at least in part, the use of G. achachairu in folk medicine and suggest that this plant is an important source of compounds with a suitable profile for development as new and effective medicinal agents to treat pain processes.

New 3,4-seco-ent-kaurene dimers from Croton micans.

From the stems of Croton micans Sw., five new 3,4-seco-ent-kaurene dimers: micansinoic acid (1), isomicansinoic acid (2), and the dimethyl (3), monomethyl (4) and monoethyl ester (5) of micansinoic acid were isolated. The structures of the new compounds were elucidated by spectroscopic data interpretation, mainly 1D and 2D NMR experiments and MS. These compounds are the first 3,4-seco-ent-kaurene dimers from a Croton species.

Antibacterial activity of chalcones, hydrazones and oxadiazoles against methicillin-resistant Staphylococcus aureus.

The increase in antibiotic resistance due to multiple factors has encouraged the search for new compounds which are active against multidrug-resistant pathogens. In this context, chalcones, dihydrochalcones, hydrazones and oxadiazoles were tested against Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus (MRSA) isolates, which were obtained from clinical laboratories and were characterized as MRSA using traditional and molecular methods. Among 65 tested compounds, two chalcones, one dihydrochalcone and two hydrazones were active against MRSA. Based on the minimal inhibitory concentration and cytotoxicity, hydrazones provided a better selectivity index than chalcones. Active hydrazones are promising antibiotic-like substances and they should be the subject of further microbiological studies.