Integrative open workflow for confident annotation and molecular networking of metabolomics MSE/DIA data.

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.

Phytochemical investigation of Nigrospora zimmermanii isolated from Poincianella pluviosa (Sibipiruna): metabolites characterisation and screening for anti-inflammatory activity.

Endophytic fungi residing symbiotically in plant tissues are promising sources of bioactive natural products. This study explored the anti-inflammatory potential of an endophytic fungus isolated from the Brazilian medicinal plant Poincianella pluviosa (Sibipiruna). The extract from the endophyte FPD13 exhibited potential ex vivo anti-inflammatory effects by inhibiting prostaglandin E2 (PGE2) release by 75.22%. Phytochemical analysis using High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) enabled the isolation and identification of three compounds, including the macrolide Nigrosporolide, the phenyl-propanol Tyrosol, and the terpene Decarestrictine A. Morphological characteristics and Internal Transcribed Spacers region (ITS) sequencing classified fungus FPD13 as Nigrospora zimmermanii. The results reveal the anti-inflammatory potential and chemical diversity of P. pluviosa endophytes, warranting further investigation into the bioactivity and structure elucidation of their bioactive metabolites.

Evaluation of the anti-inflammatory activity of Acacia polyphylla and identification of a new apigenin-3-C- glycosylated type flavonoid.

Owing to the potentially harmful adverse effects of current anti-inflammatory drugs, there is a need to identify new alternative substances. Thus, this study aimed to perform a phytochemical analysis of A. polyphylla to identify compounds responsible for its anti-inflammatory activity. Several fractions of the A. polyphylla extract were obtained and evaluated in an ex vivo anti-inflammatory assay using fresh human blood. Among the evaluated fractions, the BH fraction displayed the highest percentage of PGE2 inhibition (74.8%) compared to the reference drugs dexamethasone and indomethacin, demonstrating its excellent potential for anti-inflammatory activity. Astragalin (P1), a known 3-O-glucoside of kaempferol, was isolated from the A. polyphylla extract for the first time. In addition, a new compound (P2) was isolated and identified as the apigenin-3-C-glycosylated flavonoid. Astragalin showed moderate PGE2 activity (48.3%), whereas P2 was not anti-inflammatory. This study contributes to the phytochemical studies of A. polyphylla and confirms its anti-inflammatory potential.

Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae).

BACKGROUND: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity. PURPOSE: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus. METHODS: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity. RESULTS: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MSE spectra were compared with comprehensive databases. CONCLUSION: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.

Aporphine Alkaloids from Ocotea puberula with Anti-Trypanosoma Cruzi Potential - Activity of Dicentrine-ß-N-Oxide in the Plasma Membrane Electric Potentials.

One new aporphine, dicentrine-ß-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated in vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2 µM and reduced toxicity against NCTC cells (CC50 >200 µM - SI>11.0), similar to positive control benznidazole (EC50 of 17.7 µM and SI=10.7). Considering the promising results of dicentrine-ß-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2 h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-ß-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents.

Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease.

ETHNOPHARMACOLOGY RELEVANCE: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease. AIM OF THE STUDY: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model. MATERIAL AND METHODS: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS. RESULTS: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as ß-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results. CONCLUSION: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD.

Anti-urolithiatic and anti-inflammatory activities through a different mechanism of actions of Cissus gongylodes corroborated its ethnopharmacological historic.

ETHNOPHARMACOLOGICAL RELEVANCE: Species Cissus gongylodes has been used in the traditional medicine in South America and India for the treatment of urolithiasis, biliary and inflammatory problems without any scientific evidence. AIM OF THE STUDY: This work was developed to investigate for the first time the anti-inflammatory and anti-urolithiatic activities of leaf decoction of C. gongylodes. MATERIALS AND METHODS: Decoction was subjected to anti-inflammatory evaluation by the in vivo assay of ear oedema and quantification of the main mediators of inflammation PGE2 and LTB4, and the cytokine TNF-α. The decoction's anti-urolithiatic activity was determined by different in vitro assays to evaluate the inhibition and dissolution of the most prevalent types of kidney stones: calcium oxalate (CaOx) and struvite. Diffusion in gel technique and fresh urine of a patient with renal stone were used to investigate the inhibition and dissolution of CaOx, respectively, and the single diffusion gel growth technique was used to evaluate the inhibition and dissolution of struvite crystals. The decoction was chemically characterized by UHPLC-ESI-HRMS analysis. RESULTS: Decoction showed in vivo anti-inflammatory activity by potent decreasing the level of both the main mediators of inflammation and dose-dependent in vitro anti-urolithiatic action by inhibition and dissolution of both type of crystals, CaOx and struvite. CONCLUSIONS: Results obtained corroborate the reports of the traditional use of the decoction of Cissus gongylodes. Besides, it showed multi-target mechanisms actions, inhibition of the main inflammatory pathways, and inhibition/dissolution of the most prevalent types of crystals on urolithiasis. These actions make the decoction a promissory source to the development of new and more efficient drugs.

Anti-Inflammatory Derivatives with Dual Mechanism of Action from the Metabolomic Screening of Poincianella pluviosa.

Metabolomics approaches have become fundamental strategies for the analysis of complex mixtures, guiding the isolation of target compounds by focusing on unpublished or promising pharmacological properties. The discovery of novel anti-inflammatory agents is important due to several limitations regarding their potency, efficacy, and adverse effects. Thus, novel anti-inflammatory candidates are essential, aiming to find agents with better mechanisms of action. In this context, extracts from Poincianella pluviosa var. peltophoroides demonstrated significant in vivo anti-inflammatory potential. Thus, metabolomics analysis based on UHPLC-UV-HRFTMS data was performed for the identification of biomarkers with anti-inflammatory properties. Metabolomics-guided chromatographic process led to the isolation of novel compounds 4‴-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, as well as known derivatives rhuschalcone VI and caesalpinioflavone. Isolated compounds caused edema inhibition and neutrophil recruitment. Two of them showed better efficacy than reference drugs (indomethacin and dexamethasone). Results of in vivo experiments corroborated those obtained through metabolomics and statistical analyses guiding the isolation of substances of interest.

Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells.

Guarea macrophylla is a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves from G. macrophylla using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3ß,25-diol (1), (23S*,24S*)-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2α,3ß-diol (3), and isopimara-7,15-dien-3ß-ol (4), in which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 1-4 against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound 1 induced cytotoxic effects on tumor cells, with IC50 values of 18.3, 52.1, and 58.9 µM against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound 1 induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway.

Antileishmanial Activity and Immunomodulatory Effects of Tricin Isolated from Leaves of Casearia arborea (Salicaceae).

Bioactivity-guided fractionation of antileishmanial active extract from leaves of Casearia arborea led to isolation of three metabolites: tricin (1), 1',6'-di-O-ß-d-vanilloyl glucopyranoside (2) and vanillic acid (3). Compound 1 demonstrated the highest activity against the intracellular amastigotes of Leishmania infantum, with an IC50 value of 56 µm. Tricin (1) demonstrated selectivity in mammalian cells (SI > 7) and elicited immunomodulatory effect on host cells. The present work suggests that tricin modulated the respiratory burst of macrophages to a leishmanicidal state, contributing to the parasite elimination. Therefore, the natural compound tricin could be further explored in drug design studies for leishmaniasis treatment.

Cytotoxic and Antimicrobial Constituents from the Essential Oil of Lippia alba (Verbenaceae).

Backgroud:Lippia alba (Verbenaceae) is a plant widely used in folk medicine to treat various diseases. The present work deals with the chemical composition of the crude essential oil extracted from leaves of L. alba and evaluation of its antimicrobial and cytotoxic activities. Methods: Leaves of L. alba were extracted by hydrodistillation and analyzed by gas chromatography/mass spectrometry (GC/MS) as well as by nuclear magnetic resonance (NMR) spectroscopy. Cytotoxic and antimicrobial activities of crude essential oil were evaluated in vitro using MTT and broth microdilution assays, respectively. Results: Chemical analysis afforded the identification of 39 substances corresponding to 99.45% of the total oil composition. Concerning the main compounds, monoterpenes nerol/geraniol and citral correspond to approximately 50% of crude oil. The cytotoxic activity of obtained essential oil against several tumor cell lines showed IC50 values ranging from 45 to 64 µg/mL for B16F10Nex2 (murine melanoma) and A549 (human lung adenocarcinoma). In the antimicrobial assay, was observed that all tested yeast strains, except C. albicans, were sensitive to crude essential oil. MIC values were two to four-folds lower than those determined to bacterial strains. Conclusion: Analysis of chemical composition of essential oils from leaves of L. alba suggested a new chemotype nerol/geraniol and citral. Based in biological evidences, a possible application for studied oil as an antifungal in medicine, as well as in agriculture, is described.

7-Epiclusianone, a Benzophenone Extracted from Garcinia brasiliensis (Clusiaceae), Induces Cell Cycle Arrest in G1/S Transition in A549 Cells.

Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 µM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.

Assessing the Chemical Composition and Antimicrobial Activity of Essential Oils from Brazilian Plants-Eremanthus erythropappus (Asteraceae), Plectrantuns barbatus, and P. amboinicus (Lamiaceae).

The chemical composition and antimicrobial activity of essential oils obtained from three Brazilian plant species-leaves and branches of Eremanthus erythropappus (Asteraceae), leaves of Plectranthus barbatus, and leaves of P. amboinicus (Lamiaceae)-were determined. Analysis by GC/MS and determination of Kovats indexes both indicated δ-elemene (leaves-42.61% and branches-23.41%) as well as (-)-α-bisabolol (leaves-24.80% and stem bark-66.16%) as major constituents of E. erythropappus essential oils. The main components of leaves of P. barbatus were identified as (Z)-caryophyllene (17.98%), germacrene D (17.35%), and viridiflorol (14.13%); whereas those of leaves of P. amboinicus were characterized as p-cymene (12.01%), γ-terpinene (14.74%), carvacrol (37.70%), and (Z)-caryophyllene (14.07%). The antimicrobial activity against yeasts and bacteria was assessed in broth microdilution assays to determine the minimum inhibitory concentration (MIC) necessary to inhibit microbial growth. In addition, the crude oil of branches of E. erythropappus was subjected to chromatographic separation procedures to afford purified (-)-α-bisabolol. This compound displayed biological activity against pathogenic yeasts, thus suggesting that the antimicrobial effect observed with crude oils of E. erythropappus leaves and branches may be related to the occurrence of (-)-α-bisabolol as their main component. Our results showed that crude oils of Brazilian plants, specifically E. erythropappus, P. barbatus, and P. amboinicus and its components, could be used as a tool for the developing novel and more efficacious antimicrobial agents.

Chemical composition and in vitro cytotoxic effects of the essential oil from Nectandra leucantha leaves.

CONTEXT: Nectandra (Lauraceae) species have been used in folk medicine as an antidiarrheal, analgesic, antifungal, etc., and have many pharmacological proprieties. OBJECTIVE: Investigation of the chemical composition and cytotoxicity of essential oil from Nectandra leucantha Nees & Mart. leaves. This is the first study involving N. leucantha reported in the literature. MATERIAL AND METHODS: The essential oil of N. leucantha leaves was obtained by hydrodistillation. Its chemical composition was determined using a combination of GC/FID, GC/MS, and determination of Kovats index (KI). In vitro cytotoxic activity was evaluated against six cancer cell lines - murine melanoma (B16F10-Nex2), human glioblastome (U-87), human cervical carcinoma (HeLa), human colon carcinoma (HCT), human breast adenocarcinoma (MCF7), and human cervical tumor (Siha) as well as against one non-tumorigenic cell line - human foreskin fibroblast (HFF). RESULTS: Thirty-three compounds were identified primarily sesquiterpenes (81.41%), the main compounds being bicyclogermacrene (28.44%), germacrene A (7.34%), spathulenol (5.82%), and globulol (5.25%). Furthermore, monoterpenes were also found in the analyzed oil (12.84%), predominantly α- and ß-pinenes (6.59 and 4.57%, respectively). The crude essential oil displayed significant cytotoxic activity against B16F10-Nex2 (IC50 33 ± 1 µg/mL) and U87 (IC50 75.95 ± 0.03 µg/mL) and HeLa (IC50 60 ± 12 µg/mL) cell lines. The main identified compound, bicyclogermacrene, displayed IC50 ranging from 3.1 ± 0.2 to 21 ± 6 µg/mL. DISCUSSION AND CONCLUSION: The results indicate that the crude oils from leaves of N. leucantha displayed cytotoxic activity being bicyclogermacrene, the main compound identified in the crude oil responsible, at least in part, for this potential.

Chemical composition and cytotoxicity evaluation of essential oil from leaves of Casearia sylvestris, its main compound α-zingiberene and derivatives.

Casearia sylvestris (Salicaceae), popularly known as "guaçatonga", is a plant widely used in folk medicine to treat various diseases, including cancer. The present work deals with the chemical composition as well as the cytotoxic evaluation of its essential oil, its main constituent and derivatives. Thus, the crude essential oil from leaves of C. sylvestris was obtained using a Clevenger type apparatus and analyzed by GC/MS. This analysis afforded the identification of 23 substances, 13 of which corresponded to 98.73% of the total oil composition, with sesquiterpene a-zingiberene accounting for 50% of the oil. The essential oil was evaluated for cytotoxic activity against several tumor cell lines, giving IC50 values ranging from 12 to 153 mg/mL. Pure a-zingiberene, isolated from essential oil, was also evaluated against the tumor cell lines showing activity for HeLa, U-87, Siha and HL60 cell lines, but with IC50 values higher than those determined for the crude essential oil. Aiming to evaluate the effect of the double bonds of a-zingiberene on the cytotoxic activity, partially hydrogenated a-zingiberene (PHZ) and fully hydrogenated a-zingiberene (THZ) derivatives were obtained. For the partially hydrogenated derivative only cytotoxic activity to the B16F10-Nex2 cell line (IC50 65 mg/mL) was detected, while totally hydrogenated derivative showed cytotoxic activity for almost all cell lines, with B16F10-Nex2 and MCF-7 as exceptions and with IC50 values ranging from 34 to 65 mg/mL. These results indicate that cytotoxic activity is related with the state of oxidation of compound.

Electrophysiological responses of the Naupactus bipes beetle to essential oils from Piperaceae species.

Electrophysiological responses based on electroantennographic detection (GC-EAD) and electroantennography (EAG) analysis of Naupactus bipes beetles (Germar, 1824) (Coleoptera: Curculionidae: Brachycerinae) were used to test volatile oils of Piper gaudichaudianum, P. regnellii and P. hispidum. In the EAG experiments, female and male beetles showed significant EAG response to the three volatile oils of Piper species, with the females' responses slightly higher than the males'. The experiments with GC-EAD revealed that some terpenoids (namely, alpha-pinene, beta-pinene, myrcene, alpha-copaene and germacrene) present in the leaf essential oils of the Piper species are perceptible to female and male beetles.

Essential oils from Schinus terebinthifolius leaves - chemical composition and in vitro cytotoxicity evaluation.

CONTEXT: In folk medicine, Schinus terebinthifolius Raddi (Anacardiaceae), has been used as a remedy for ulcers, respiratory problems, wounds, rheumatism, gout, diarrhea, skin ailments and arthritis, as well as to treat tumors and leprosy. OBJECTIVE: To investigate the chemical composition and cytotoxicity of essential oil from leaves of S. terebinthifolius as well as the identification of active compounds from this oil. MATERIAL AND METHODS: Essential oil from S. terebinthifolius leaves, obtained by hydrodistillation using a Clevenger-type apparatus, was characterized in terms of its chemical composition. Also, the crude oil was subjected to chromatographic separation procedures to afford an active fraction composed of α- and ß-pinenes. These compounds, including hydrogenation (pinane) and epoxydation (α-pinene oxide) derivatives from α-pinene, were tested in vitro against murine melanoma cell line (B16F10-Nex2) and human melanoma (A2058), breast adenocarcinoma (MCF7), leukemia (human leukemia (HL-60) and cervical carcinoma (HeLa) cell lines. RESULTS: Forty-nine constituents were identified in the oil (97.9% of the total), with germacrene D (23.7%), bicyclogermacrene (15.0%), ß-pinene (9.1%) and ß-longipinene (8.1%) as the main compounds. The crude essential oil showed cytotoxic effects in several cell lines, mainly on leukemia and human cervical carcinoma. Fractions composed mainly of α- and ß-pinenes as well as those composed of individually pinenes showed effective activities against all tested cell lines. Aiming to determinate preliminary structure/activity relationships, α-pinene was subjected to epoxydation and hydrogenation procedures whose obtained α-pinene oxide showed an expressive depression in its cytotoxicity effect, similar as observed to pinane derivative. DISCUSSION AND CONCLUSION: The obtained results indicated that the monoterpenes α- and ß-pinenes could be responsible to the cytotoxic activity detected in the crude oil from leaves of S. terebinthifolius. In addition, it was possibly inferred that the presence of double bond in their structures, mainly at endocyclic position, is crucial to cytotoxic potential detected in these derivatives.

The genus Caesalpinia L. (Caesalpiniaceae): phytochemical and pharmacological characteristics.

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia.

Intraspecific variation in the essential oils from Drimys brasiliensis leaves and stem barks.

The essential oils from leaves and stem barks of Drimys brasiliensis Miers (Winteraceae), collected in July and December 2008, were analyzed by GC/FID and GC/MS. The stem bark oils were composed mainly of monoterpenes (July, 45 +/- 3%; December, 92 +/- 4%), while the oils from leaves showed the predominance of sesquiterpenes (July, 47 +/- 1%; December, 55 +/- 1%). The variation in the relative amount of constituents could be associated, at least in part, to several microclimatic parameters such as precipitation, temperature and/or phenological state, which were different for each collection of D. brasiliensis.