In the present work, dried aerial parts of Baccharis ligustrina (Asteraceae) were subjected to microwave assisted extraction (MAE) using aqueous solution of 1-butyl-3-methylimidazolium bromide (BMImBr) and the obtained extract was successively partitioned using hexane and EtOAc. Using reduced amounts of extracts and efficient chromatographic steps, four acyl C6C3 derivatives (n-hexacosyl ferulate, n-hexacosyl, n-octacosyl, and n-triacontyl p-coumarates) were obtained from hexane phase whereas two C6C3 acids (ferulic and p-coumaric) were obtained from EtOAc phase. Isolated phenylpropanoids were evaluated against amastigote forms of parasite Trypanosoma cruzi. As result, it was observed that p-coumaric and ferulic acids were inactives whereas alkyl derivatives displayed EC50 values of 6.5 µmol L-1 (n-octacosyl p-coumarate), 9.3 µmol L-1 (n-triacontyl p-coumarate), 15.7 µmol L-1 (n-hexacosyl p-coumarate), and 32.2 µmol L-1 (n-hexacosyl ferulate). All tested compounds displayed reduced toxicity against NCTC cells (CC50 > 200 mmol L-1).

Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo anti-inflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7) showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.

Although the genus Duguetia is well known for producing alkaloids as chemical constituents, there are no reports of alkaloids identified in the species D. lanceolata. Thus, aiming to identify the chemical composition of this species, the dereplication of alkaloidic phase was performed by use of ultra-high performance liquid chromatography high resolution electrospray ionization tandem mass spectrometry (UHPLC-HR-ESI-MS/MS) and 1H nuclear magnetic resonance (NMR). The chromatographic fractionation of the alkaloid extract from Duguetia lanceolata (Annonaceae) leaves afforded four fractions (I-IV) that were shown to be composed of aporphine alkaloids. 1H NMR analysis and UHPLC-HR-ESI-MS/MS based dereplication allowed the identification of eight alkaloids: glaucine (1), norglaucine (2), isocorydine (3), N-methyllaurotetanine (4), oxoglaucine (5), liriodenine (6), lanuginosine (7), dehydroglaucine (8). Compounds 2,3, 4,6 and 7 were described for the first time in this species, while alkaloids 1,5 and 8 are newly discovered in the genus Duguetia. Additionally, the antiparasitic activity of the four fractions was evaluated in vitro against Leishmania infantum and Trypanosoma cruzi. Fraction I, composed exclusively by 1, displayed activity against Leishmania infantum and Trypanosoma cruzi intracellular amastigotes, with half maximal inhibitory concentration (IC50) values of 7.5 and 28.6 µg mL-1, respectively. Fraction IV (constituted by 2,3 and 4) showed activity against promastigotes of Leishmania infantum with IC50 value of 50.0 µg mL-1, while fraction II (constituted by 5 and 6) showed activity against trypomastigotes of Trypanosoma cruzi, with IC50 values of 83.0 µg mL-1. This work showed that fragmentation in UHPLC-HR-ESI-MS/MS combined with 1H NMR analysis of fractions is useful for identifying alkaloids in mixtures. Additionally, it was also demonstrated the potential of aporphine alkaloids from Duguetia lanceolata St. -Hil (Annonaceae) in the search for new drug candidates for neglected diseases.

Meliaceae representatives are economically important in several aspects including the production of highly prized woods (mahogany, cedar, etc.), constituents for cosmetics, and insecticides. The present study aimed to verify the chemical composition as well as leishmanicidal and cytotoxic potential of essential oils from leaves of two different populations of Guarea macrophylla collected at cities of São Paulo (population I) and Cubatão (population II), São Paulo State, Brazil. Chemically, the oils showed the predominance of sesquiterpenes: cis-β-guaiene, bicyclogermacrene, viridiflorol, and isolongifolan-7α-ol from population I and α-copaene, E-caryophyllene, cis-β-guaiene, and γ-amorphene from population II. In vitro antileishmanial activity against promastigote forms of Leishmania (L.) amazonensis of essential oils was evaluated and displayed 50% effective concentration (EC50) values ranging from 11.8 to 20.5 µg mL-1. Furthermore, toxicity against peritoneal macrophages of BALB/c mice was observed, with 50% cytotoxic concentration (CC50) ranging from 17.7 to > 100 µg mL-1. Multivariate statistical analysis revealed the influence of each constituent of the oils against L. amazonensis being 1,10-di-epi-cubenol, α-amorphene, E-caryophyllene, isopimara-7,15-diene, and β-elemene associated with the antileishmanial potential.

The present study aimed to investigate the presence of compounds with antitumor activity in the plant Caesalpinia pluviosa var. peltophoroides. From bioactivity guided studies it was possible to isolate a new biflavonoid, named caesalpinioflavone, whose chemical structure was determined by spectroscopic (1H and 13C nucler magnetic ressonace, homonuclear correlation spectroscopy and heteronuclear multiple-bond correlation spectroscopy) and spectrometric (high resolution electrospray ionization mass) methods. According to in vitro assays, caesalpinioflavone was effective in reducing the cell viability of tumor cell lines A549, MCF7, Hst578T and HTC. This effect was consequent of cell cycle arrest in G1/S transition (A549 and MCF7) and cytotoxic activity (Hs578T and HTC). Taken together, these data indicate that caesalpinioflavone has a promising antitumor activity.

Essential oils of ripe fruits from Schinus terebinthifolius (Anacardiaceae), obtained using a pilot extractor and a Clevenger apparatus were chemically characterized. Due the high amount of (-)- α-pinene in both oils, this monoterpene was tested against the protozoan parasite Trypanosoma cruzi, showing a moderate potential (IC50 63.56 µg/mL) when compared to benznidazole (IC50 43.14 µg/mL). Otherwise, (-)- α-pinene oxide did not showed anti-trypanosomal activity (IC50 > 400 µg/mL) while (-)-pinane showed an IC50 of 56.50 µg/mL. The obtained results indicated that the epoxydation of α-pinene results to the loss of the anti-parasitic activity while its hydrogenation product, contributed slightly to the increased activity.

The essential oils from the leaves of six species of the Baccharis genus (B. dracunculifolia, B. microdonta, B. regnelli, B. schultzii, B. trimera, and B. uncinella), collected in the "Campos de Altitude" of the Atlantic Forest (SP), were extracted using hydrodistillation procedures and analyzed by GC and GC/MS. There was a predominance of sesquiterpenes in all studied oils as b-elemene in B. dracunculifolia and B. regnelli, a-humulene in B. trimera, g-gurjunene in B. schultzii, bicyclogermacrene in B. regnelli, d-cadinene in B. regnelli and B. uncinella, spathulenol in B. schultzii, caryophyllene oxide in B. microdonta and guaiol in B. uncinella. However, a high amount of monoterpenes was also observed in B. uncinella (a-pinene), B. regnelli (d-car-3-ene) and B. schultzii (limonene). The chemical compounds of the essential oils of B. schultzii, B. regnelli and B. microdonta are described for the first time in this work.

Bioguided fractionation of the extracts from leaves of Piper mollicomum and Piper lhotzkyanum against the fungi Cladosporium cladosporioides and C. sphaerospermum afforded seven bioactive compounds, four being chromenes: methyl 2,2-dimethyl-2H-chromene-6-carboxylate, methyl 8-hydroxy-2,2-dimethyl-2H-chromene-6-carboxylate, 2-methyl-2-[4'-methyl-3'-pentenyl]-2H-1-benzopyran-6-carboxylic acid, 2,2-dimethyl-2H-chromene-6-carboxylic acid, one a dihydrochalcone: 2',6'-dihydroxy-4'-methoxydihydrochalcone, and two flavanones: 7-methoxy-5,4'-dihydroxy-flavanone and 7,4'-dimethoxy-5-hydroxy-flavanone. The structures of the bioactive isolated derivatives were elucidated by interpretation of their NMR data [¹H and 13C (BBD, DEPT 135º)], and mass spectral data as well as by comparison with data described in the literature.

A 2-hidroxi-4,6-dimetoxiacetofenona foi isolada de folhas de Peperomia glabella (família Piperaceae). A substância cristaliza no grupo espacial P1 com duas moléculas na unidade assimétrica. A análise estrutural revela uma rede bidimensional infinita no plano (011), estabilizada por ligações de hidrogênio inter-moleculares ao longo da direção [100] e interações de van der Waals ao longo da direção [011]. As moléculas apresentam fortes ligações de hidrogênio intra-moleculares [O1-HO1...O4 = 1,53(2) Å e O5-HO5...O8 = 1,38(2) Å]. A conformação molecular foi analisada usando o MOGUL, uma base de dados de geometria molecular derivada do CSD (Cambridge Structural Database).

The 2-hydroxy-4,6-dimethoxyacetophenone was isolated from the leaves of the Peperomia glabella (Piperaceae family). The molecule crystallizes in the space group P1 with two independent molecules in the asymmetric unit. The structural analysis reveals an infinite two-dimensional network in the (011) plane, stabilized by intermolecular hydrogen bonds along [100] and van der Waals interactions along [011]. The molecules present strong intra-molecular hydrogen bonds [O1-HO1...O4 = 1.53(2) Å and O5-HO5...O8 = 1.38(2) Å]. The molecular conformation was analyzed using the MOGUL, a knowledge base of molecular geometry derived from the CSD (Cambridge Structural Database).