Dipteryx alata Vogel is a native fruit from Brazil, which has been poorly investigated concerning its phenolic composition and the biological effects of its pulp + peel. Thus, in this study we evaluated the antioxidant activity and total phenolic content of the D. alata pulp + peel extracts obtained with different solvents, as well as determined the phenolic compounds by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis. In addition, cytotoxic effects of D. alata pulp + peel extract on non-tumor and cancer cell lines were investigated for the first time. The results showed that phenolic compounds can be efficiently extracted from pulp + peel of D. alata by organic solvent-water mixtures as an extraction system. The developed UHPLC-MS/MS method allowed the quantification of eighteen phenolic compounds in D. alata pulp + peel extract for the first time, which luteolin and trans-cinnamic acid were predominant. In addition, D. alata pulp + peel extract exhibited better cytotoxity against SiHa and C33A cervical cancer cell lines, while weak cytotoxicity was noticed against non-tumor HaCaT and L929 cell lines, pointing out its safety and providing preliminary evidence of its anticancer potential. Our findings indicate that D. alata pulp + peel can be explored as a natural source of phenolic compounds with promising antioxidant and cytotoxic properties.

Fungi and bacteria are well-known pathogens for plants, fruits, and animals, including humans. In this context, the prospection of antimicrobial agents is crucial to provide new alternatives for the treatment of microbial diseases. Hence, selenium- and tellurium-containing compounds are underexploited and herein, antimicrobial activity of several organochalcogenated compounds was evaluated against Gram-negative and Gram-positive bacteria and fungi. A direct comparison between Se- and Te-containing compounds was performed, as well as structure-activity relationship studies. Among assayed compounds, secondary Se-amines LQ16 and LQ20 and secondary Te-amine LQ28 showed excellent results against a variety of fungi, while primary Te-amine LQ10 demonstrated promising results against bacteria. These results suggest organoselenides and organotellurides may be used for the development of new antimicrobial agents.

A series of novel 1-(substituted-phenyl)-3-(4,5-dihydro-1,3-oxazol-2-yl)-9H-β-carboline (8a-8i) and 1-(substituted-phenyl)-3-(5,6-dihydro-4H-1,3-oxazin-2-yl)-9H-β-carboline (9a-9h) derivatives, as well as their respective N-(chloroalkyl)-1-(substituted-phenyl)-9H-β-carboline-3-carboxamide precursors (6a-6i and 7a-7h), were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. Compounds 8d, 8i, 9e and 9h exhibited significant activity for both promastigote and amastigote forms, with IC50 (50% inhibitory concentration) values ranging from 2.9 to 23.0 µM. In addition, spin label electron paramagnetic resonance (EPR) spectroscopy studies were carried out for the most active compounds against L. amazonensis promastigotes. The studies indicated that the tested compounds cause strong stiffness in the parasite plasma membrane and are capable of inducing internal metalloproteins oxidation of the parasite, resulting in their cross-linking to skeletal proteins. Compounds 8d and 8i produced the largest effect, showing that the presence of oxazoline group at C-3 of β-carboline nucleus is important for antileishmanial activity.

In this work a series of 28 novel pyrazolo[3,4-d]pyridazin-7-ones were synthesized and tested against Leishmania amazonensis (strain WHOM/BR/75/JOSEFA) in promastigote and axenic amastigote forms. Five compounds were active against both cellular forms with IC50 (inhibitory concentration growth of 50%) values of 20.2, 11.7, 16.2, 29.5 and 40.3 µM for promastigote and 17.4, 25.2, 3.84, 21.8 and 22.7 µM for axenic amastigote. All compounds were studied by the Lipinski rule, cytotoxicity both in silico and in vitro to fibroblast line (L929) and macrophages (J774A1), and the most active compound showed a selectivity index of 59.9.

Chagas' disease is a parasitic disease with unsatisfactory treatment, mainly in chronic stage. This study aimed to evaluate the trypanocidal activity and action mechanisms of α/β-amyrin and its semi-synthetic derivatives, together with four isolated natural triterpenes, tested against trypomastigote and amastigote forms. The structure-activity relationship was suggested and cytotoxicity was measured. In general, greater polar compounds may have improved the selectivity to the protozoan. Action mechanisms were only performed for the amastigotes of Trypanosoma cruzi by evaluating the ultrastructural alterations, membrane permeability, mitochondrial membrane potential and cell volume, since the majority of compounds displayed promising antiamastigote activities. Triterpenes promoted changes on mitochondrial membrane potential and ultrastructural features that suggest autophagy processes. Both combinations between α/β-amyrin and 3-O-acetyl-11-oxo-α/β-amyrin and 3-O-acetyl-α/β-amyrin with benznidazole displayed synergistic effects against amastigotes and antagonistic effects on LLCMK2 cells. The antiamastigote activities, chemical derivatization, drug combinations and action mechanisms revealed to be crucial approaches toward this chronic disease.

Copaiba oil, an oleoresin extracted from Copaifera genus, has been widely used in popular medicine for the treatment of several diseases. The aim of this study was to investigate the antifungal activity of the copaiba oil and its isolated compounds caryophyllene oxide, copalic acid and acetoxycopalic acid against Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum gypseum strains, using microdilution method and microscopy techniques. It was found that the copaiba oil and the copalic acid were active against dermatophytes by minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) tests. The MIC and MFC of copaiba oil against T. rubrum, T. mentagrophytes and M. gypseum were 125 µg mL-1 (250 µg mL-1), 500 µg mL-1 (500 µg mL-1) and 250 µg mL-1 (250 µg mL-1), respectively. For copalic acid, the MIC and MFC were 50 µg mL-1 (100 µg mL-1), 100 µg mL-1 (100 µg mL-1) and 50 µg mL-1 (100 µg mL-1), respectively. Fluorescence microscopy and scanning electronic microscopy were used to investigate inhibition on hyphal growth by compounds, copaiba oil and copalic acid, showing a strong inhibition and an irregular growth pattern. Cell wall, cytoplasmic membrane and intracellular contents were also damaged. In conclusion, copaiba oil and copalic acid showed great activity against dermatophytes, being potential compounds for the development of antifungal drugs.

Bioguided fractionation of a hydroethanolic extract from the stem bark of Croton echioides Baill. led to isolation of the new indole alkaloid N-trans-feruloyl-3,5-dihydroxyindolin-2-one as a stereoisomeric mixture and the known alkaloids N-trans-p-coumaroyl-tryptamine, N-trans-p-coumaroyl-5-hydroxytryptamine, N-trans-4-methoxy-cinnamoyl-5-hydroxytryptamine, N-trans-feruloyl-5-hydroxytryptamine (moschamine), from the ethyl acetate fraction. The flavonoids 3-o-methyl kaempferol, 3-o-methyl quercetin, 3,7-di-o-methyl quercetin and 3,3'-di-o-methyl quercetin, together with the benzoic acid derivatives 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid and 4-hydroxy-3,5-dimethoxybenzoic acid were also isolated. Alkaloids and the flavonoids showed strong antioxidant properties in vitro radical scavenging assay (2,2-diphenyl-1-picrylhydrazyl, DPPH), with IC50 values ranging from 9.2 to 17.5 µmol L-1, lower than those of the positive control Trolox (IC50 = 17.9 µmol L-1). Alkaloids showed cytotoxic activity against the HCT-116 human cancer cell line, with IC50 values ranging from 86.8 to 210.7 µmol L-1. Compound N-trans-4-methoxy-cinnamoyl-5-hydroxytryptamine was the most active, with an IC50 value of 86.8 µmol L-1.

The isolation and structure determination of new cyclic peptide alkaloid ixorine, along with five known constituents frangulanine, syringaresinol, cinnamtannin B-1, daucosterol and mannitol from the branches of Ixora brevifolia are described. The cyclic peptide frangulanine is being described for the first time in the Rubiaceae family. The structures were elucidated on their spectral data basis, mainly one- (1H, 13C, DEPT) and two-dimensional (COSY, NOESY, HSQC and HMBC) nuclear magnetic resonance (NMR) and by comparison with data from the literature. The mixture of two cyclopeptide alkaloids showed weak activity against Leishmania amazonensis.

The chemical study of the orchid Maxillaria picta resulted in the isolation of the bioactive stilbenes phoyunbene B and phoyunbene C, in addition to four phenolic acids, one xanthone, steroidal compounds and two triterpenes. Crude extract, fractions, subfractions and the isolated xanthone were evaluated for anticancer activity against human tumor cell lines and against evolutionary forms of T. cruzi and L. amazonensis. The structures of the compounds were determined by GC-MS, and ¹H NMR, 13C NMR spectral methods as well as bidimensional techniques.

This study investigated the antiviral potential of fractions and eupomatenoid-5 obtained from Piper regnelli (Miq.) C. DC., Piperaceae, leaves against bovine herpesvirus-1 (BHV-1) and poliovirus. VERO cell monolayers in 96-well cell culture plates were infected with BHV-1 or poliovirus and incubated in the presence and absence of samples for 48 h. The cells were then fixed and stained with sulforhodamine B, and the virus-induced cytopathic effect was measured in a 96-well plate reader at 530 nm. Cytotoxicity was assessed by incubating the cell monolayers with samples for 72 h. The hexane, chloroform, chloroform/ethyl acetate (19:1), and chloroform/ethyl acetate (9:1) fractions showed activity against BHV-1. The chloroform, chloroform/ethyl acetate (19:1), chloroform/ethyl acetate (9:1), chloroform/ethyl acetate (1:1), and ethyl acetate fractions were active against poliovirus. The chloroform/ethyl acetate (9:1) fraction presented the best selectivity index for both viruses. The present study reports the antiviral activity of the extract and fractions of P. regnelli leaves.

A continuidade do estudo fitoquímico de P. prunifolia com a análise dos extratos etanólicos obtidos a partir de suas raízes e galhos levou ao isolamento de cinco alcaloides indol-β-carbolínicos dos quais, dois derivados, o 10-hidróxi-iso-deppeaninol e o N-óxido-10-hidróxi-antirhina são descritos pela primeira vez. As estruturas foram determinadas por análise de técnicas espectroscópicas de IV, EMAR e RMN (¹H e 13C, 1D e 2D). A avaliação da atividade frente à Leishmania amazonensis e Trypanosoma cruzi, mostrou que os extratos brutos e os alcaloides 14-oxoprunifoleína e estrictosamida inibiram as formas promastigotas de L. amazonensis, com valores de CI50 de 16,0 e 40,7 µg per mL, respectivamente.

The continuity of the phytochemical study of crude extracts of P. prunifolia's roots and branches led to the isolation of five indole-β-carboline alkaloids. Among them, the 10-hydroxy-iso-deppeaninol and N-oxide-10-hydroxy-antirhine derivatives are described here for the first time. The structures were achieved through 1D and 2D NMR, IR and HRMS analyses. The branches and roots crude extracts and the alkaloids 14-oxoprunifoleine and strictosamide showed selective activity against L. amazonensis, with IC50 values of 16.0 and 40.7 µg per mL, respectively.

Endophytic fungi inhabit vegetable tissues or organs, without causing them any harm. Endophytes can co-evolve with plant hosts and possess species-specific interactions. They can protect the plant from insect attacks and diseases, and are also able to produce substances of biotechnological interest. In folk medicine, the bark, roots and fruits of Sapindus saponaria is used to produce substances with anxiolytic, astringent, diuretic and expectorant properties, as well as tonics, blood depuratives and cough medicine. This study evaluated the diversity of endophytic fungi present in the leaves of S. saponaria L. and observed the colonization of host plants by endophytes, using light and scanning electron microscopy. We verified that these fungi are found in intercellular and intracellular spaces. The genera of some isolates of S. saponaria were identified mainly by sequencing of ITS region of rDNA and, when possible, also by their microscopic features, as follows: Cochliobolus, Alternaria, Curvularia, Phomopsis, Diaporthe and Phoma. Phylogenetic analysis showed the existence of genetic variability of the genera Phomopsis and Diaporthe and interspecific variation among the Curvularia, Alternaria and Phoma, belonging to family Pleosporaceae.

O estudo fitoquímico das folhas de Calycorectes psidiiflorus (O. Berg) Sobral, Myrtaceae, resultou no isolamento e identificação de: sesquiterpeno [8-hidroxicalameneno (1)], triterpenos [α-amirina (2a) e β-amirina (2b)], flavonóide [3-O-α-ramnopiranosil-7-O-bglucopiranosil canferol (3)], e alcalóide [1,2,3,4-tetraidro-1-metil-β-carbolina (4)]. As estruturas das substâncias isoladas foram elucidadas com base nos seus dados de RMN em comparação com os da literatura. A substância 8-hydroxicalameneno apresentou atividade antibacteriana (MIC = 7,8 µg/mL) e antifúngica (MIC = 15,6 µg/mL).

The phytochemical study of Calycorectes psidiiflorus (O. Berg) Sobral leaves resulted in isolation and identification of the sesquiterpene 8-hydroxycalamenene (1), triterpenes α-amyrin (2a) and β-amyrin (2b), flavonoid 3-O-α-rhamnopyranosyl-7-O-β-glucopyranosyl kaempferol (3), and of the alkaloid 1,2,3,4-tetrahydro-1-methyl-β-carboline (4). The structures of the isolated compounds were elucidated based on their spectroscopic NMR data and comparison with those reported in literature. Substance 1 presented antibacterial (MIC = 7.8 µg/mL) and antifungal (MIC = 15.6 µg/ mL) activities.

The antimicrobial properties of the hexane, hexane/EtOAc and methanol fractions of the fresh petioles of Sagittaria montevidensis ssp montevidensis (Alismataceae) were evaluated against fungi and Gram-negative and Gram-positive bacteria. A new abietatriene-type diterpenoid, 3β,7α-dihydroxi-abieta-8,11,13-triene and the known 3β-hydroxy-abieta-8,11,13-trien-7-one were isolated from the most active fraction tested and the structures of these compounds were elucidated by data including IR, EIMS, and 1D and 2D NMR spectra.

A investigação fitoquímica das raízes de Spathelia excelsa levou ao isolamento das cromonas 10(2,3-epóxi-3-metilbutanil)spatheliacromeno e 10(2,3-diidroxi-3-metilbutanil) metoxispatheliacromeno (5-metoxispatheliabiscromeno); o limonóide desacetilspathelinae epímero C-21 do protolimonóide 3β-angeloiloxi-7α,24,25-triidroxi-21,23-óxido-14,18-cicloapotirucal-21-hemiacetal; os alcalóides 7,8-dimetoxiflindersina, casimiroinaeN-methyl-4,7,8-trimetoxiquinolino-2(1H)-ona, além da mistura de β-sitosterol e stigmasterol. Nos ensaios biológicos sobre a forma promastigosta de Leishmania braziliensis, desacetilspathelina apresentou atividade moderada e sobre a forma epimastigota de Trypanossoma cruzi, 10(2,3-epóxi-3-metilbutanil)spatheliacromeno apresentou atividade forte (IC50= 11 µg mL-1).

Phytochemical investigation from roots of Spathelia excelsa yielded the chromones 10(2,3-epoxy-3-methylbutanyl) spatheliachromen and 10(2,3-dihydroxy-3-methylbutanyl) methoxyspatheliacromen (5-methoxyspatheliabischromen); limonoid deacetylspathelin and protolimonoid C-21-epimers 3β-angeloyloxy-7α,24,25-trihydroxy-21,23-oxide-14,18-cycloapotirucall-21-hemiacetal; the alkaloids 7,8-dimethoxyflindersin, casimiroin and N-methyl-4,7,8-trimethoxyquinolin-2(1H)-one, besides a mixture of β-sitosterol and stigmasterol. Assays on promastigote forms of Leishmania braziliensis, deacetylspathelin showed moderate activity; and on epimastigote forms of Trypanossoma cruzi, 10(2,3-epoxy-3-methylbutanyl)spatheliachromen exhibited strong activity (IC50 = 11 µg mL-1).