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Species from the Ocotea genus have shown scientific evidence of anti-inflammatory activity through a promising mechanism of action. This study is the first in vivo evaluation of the anti-inflammatory potential and mechanism of action of extracts and essential oils from the leaves and bark of O. diospyrifolia. We isolated and identified compounds from the leaf and bark extracts and chemically characterized these extracts by ultra high-performance liquid chromatography–high-resolution mass spectrometry (UPLC-HRMS). Additionally, the essential oils were characterized by gas chromatography–mass spectrometry (GC–MS). Nine compounds (1-9) were isolated; among them, a new compound (9) was elucidated as 6aS,7S-(-)-11-hydroxy-7-methoxy-1,2-methylenedioxy-aporphine, named as diospirifoline. The aporphine substitution pattern found in diospirifoline, with substitution at C-7, was identified for first time in the Ocotea genus. Mururin A(1) and salsoline (5) were also isolated for the first time in this genus. The biosynthetically linked alkaloids coclaurine (7), reticuline (6), and isoboldine (8) were found to be 6aR-(-) isomers, which is different from the 6aS-(+) isomers that are most often found in other Ocotea spp. UPLC-HRMS analysis detected various classes of compounds in the leaf and bark extracts, such as flavonolignans, flavonoids, chlorogenic acids, alkaloids, and many other unidentified compounds. The GC–MS analysis revealed that both leaf and bark essential oils contained α-phellandrene as the major compound and that the chemotaxonomic marker of the Lauraceae family, the phenylpropanoid safrole, was not detected. Furthermore, some of the compounds identified in the extracts and essential oils have known anti-inflammatory activities, such as 5-caffeoylquinic acid, quercitrin, α-humulene, and (E)-caryophyllene. Indeed, the leaf extract, its ethyl acetate fraction, and the essential oils showed in vivo anti-inflammatory activity through the dual inhibition of edema and neutrophil recruitment, suggesting the inhibition of main inflammatory pathways. This mechanism of action is associated with a better efficacy and safety profile than that of the currently available anti-inflammatory drugs. The extract and essential oils of O. diospyrifolia showed high chemical diversity and a promising anti-inflammatory mechanism of action; thus, clearly indicating that this species should be further investigated.

This work describes the chemical and biological investigations of leaves and stems of Macrolobium latifolium (Vogel). The DCM, EtOAc soluble fractions obtained by liquid-liquid partition the crude methanolic extract of this species were submitted to usual chromatographic techniques which permitted to isolate an unusual 5,7-dihydroxychromone-3α- d -C-glucoside, named macrolobin, along with the known compounds identified as β-taraxerol, friedelin, stigmasterol, β-sitosterol, campesterol, and apigenin. The structures of all compounds were elucidated by 1H, 13C, HSQC and HMBC NMR spectra, IR spectra data analysis, and MS. Furthermore, the chemical profile from fatty acids and/or triglycerides fraction was also determined after transesterification. The reaction products were subjected to GC-FID and GC–MS permitted to detected methyl palmitate as the main fatty acid derivate present in the oil and, lauric (7.52 %), octadecanoic (17.15 %), docosanoic (5.36 %), tricosanoic (11.83 %) and tetracosanoic as minor methyl esters. Concerning the biological activities, the organic soluble fractions and macrolobin displayed antimicrobial activity against Salmonella enterica, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli (MIC values 125−1000 μg.mL−1) and, macrolobin exhibited significant acetylcholinesterase inhibition (IC50 0.8 μM). These findings indicate M. latifolium can contribute with the development of new bioactive compounds, especially the AChE inhibition.

Hundreds of millions of people worldwide are affected by Chagas' disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (-3.38), corroborating with IC50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development.

Ferulic acid (FA) is a natural hydroxycinnamic acid widely found in medicinal and edible plants. Several experts have reported the biological potential of FA, including antioxidant and antimicrobia...

The ubiquitous compound 4-hydroxy-3-methoxycinnamic acid, also known as ferulic acid (FA), constitutes a bioactive ingredient of many foods that may offer beneficial effects against disorders related to oxidative stress, including cancer, diabetes, and neurodegenerative diseases. This review discusses the antioxidant properties of FA, establishing relationships to several biological activities already described for this natural product. Next, 387 naturally occurring compounds, all isolated from plants and published between 1990 and 2015, the structures of which bear 1 or more feruloyl moieties, are covered in this review along with their structural formulas, botanical sources, and bioactivities. The compounds' distribution, structural patterns, bioactivities, and perspectives on food research are also succinctly discussed.

This work describes the isolation of pure bergenin from Peltophorum dubium roots with good yields and its further derivatization through Williamson synthesis. The alkyl derivatives of the bergenin were identified by nuclear magnetic resonance and mass spectrometry data analysis. Among them, three derivatives were reported for the first time herein, 8,10-dihexyl-bergenin, 8,10-didecyl-bergenin, and 8,10-ditetradecyl-bergenin, along with three previously reported ones (8,10-dimethylbergenin, 8-methylbergenin, 8,10-dioctyl-bergenin). Most derivatives of the bergenin displayed moderate cytotoxicity against Artemia salina, except the 8,10-dihexyl-bergenin (lethal concentration doses for 50% (LC50) = 70.55 µg mL-1). The antimicrobial assay showed that all derivatives selectively inhibited the Gram-positive bacteria Staphylococcus aureus, and two of them (8,10-dihexyl-bergenin and 8,10-didecyl-bergenin) had promising activities (minimum inhibitory concentration (MIC) = 5.1-6.2 µmol L-1). In addition, bergenin displayed interesting inhibition on acetylcholinesterase (half maximal inhibitory concentration (IC50) = 141.19 ± 0.41 µmol L-1), while its semi-synthetic derivatives displayed modest activity. Our results revealed that the antibacterial activity of bergenin could be greatly improved through its structural modification.

Labdane diterpenes and their derivatives have shown remarkable biological activities and are useful as chiral building blocks for the synthesis of a variety of bioactive compounds. There is great interest in developing biocatalyst technology to achieve regio- and stereoselective hydroxylation of unactivated C-H bonds in complex natural products, since the functionalization of unactivated C-H bonds generally requires hard reaction conditions and highly reactive oxidizing agents, which are limited regarding the control of regio- and stereoselectivity. Filamentous fungi are efficient biocatalysts capable of catalyzing a wide variety of hydroxylation reactions, and the use of whole cell biocatalysts provides advantages regarding cofactor regeneration and is much less expensive. Therefore, the goal of this study was to select biocatalysts to develop biotransformation processes that can be scalable under mild reaction conditions for hydroxylation of a labdane diterpene, 3β-acetoxy-copalic acid, which contains the trans-decalin moiety and a side chain dienic system appropriate for the preparation of a variety of compounds. Biotransformation processes were carried out and five filamentous fungi were selected as capable of producing hydroxylated diterpenes at positions C-3, C-6, C-7 and C-18 of the trans-decalin moiety and C-13 of the side chain dienic system. Hydroxylation reactions occurred with regio- and stereoselectivity by using some fungi that produced only the 6α, 7α and 13α-hydroxyl derivatives. The chemical structures of the hydroxylated diterpenes were determined from spectrometric and spectroscopic data, and the relative stereochemistry of stereogenic centers was established from coupling constants, by NOE-diff experiments and/or by computational calculations.

Natural coumarins are present in remarkable amounts as secondary metabolites in edible and medicinal plants, where they display interesting bioactivities. Considering the wide enzymatic arsenal of filamentous fungi, studies on the biotransformation of coumarins using these microorganisms have great importance in green chemical derivatization. Several reports on the biotransformation of coumarins using fungi have highlighted the achievement of chemical analogs with high selectivity by using mild and ecofriendly conditions. Prompted by the enormous pharmacological, alimentary, and chemical interest in coumarin-like compounds, this study evaluated the biotransformation of nine coumarin sca olds using Cunninghamella elegans ATCC 10028b and Aspergillus brasiliensis ATCC 16404. The chemical reactions which were catalyzed by the microorganisms were highly selective. Among the nine studied coumarins, only two of them were biotransformed. One of the coumarins, 7-hydroxy-2,3-dihydrocyclopenta[c]chromen-4(1H)-one, was biotransformed into the new 7,9-dihydroxy-2,3-dihydrocyclopenta[c]chromen-4(1H)-one, which was generated by selective hydroxylation in an unactivated carbon. Our results highlight some chemical features of coumarin cores that are important to biotransformation using filamentous fungi.

The filamentous fungus Trametes versicolor is a rich source of laccase (Tvlac). Laccases catalyze reactions that convert substituted phenol substrates into diverse derivatives through aromatic oxidation. We investigated methyl p-coumarate, methyl ferulate, and methyl caffeate biotransformation by Trametes versicolor ATCC 200801. Despite substrate similarity, the biotransformation reactions varied widely. Only methyl p-coumarate was converted into three derivatives. We isolated and identified the chemical structures of such derivatives by NMR and IR analysis. Hydroxylation, methylation, and hydrolysis were the main reactions resulting from the studied biotransformation. We also analyzed the interactions between Tvlac (PDB ID: 1GYC) and the three phenolic substrates by molecular docking simulations. The substituents in the phenol ring influenced substrate conformation and orientation in the Tvlac site. The biotransformation reaction selectivity correlated with the different binding energies to the Tvlac site. Our results demonstrated that docking studies successfully predict the biotransformation of cinnamic acid analogs by T. versicolor.

This study reports on the chemical composition and antimicrobial activity of the essential oil from Artemisia absinthium L. leaves AA EO collected in Brazil against a representative panel of cariogenic bacteria. The minimum inhibitory concentrations MICs were determined by the broth dilution method in 96-well microplates. AA EO was inactive against most of the investigated oral pathogens, but it displayed moderate activity against Streptococcus mutans MIC = 250 μg/mL and very promising activity against Streptococcus mitis MIC = 62.5 μg/mL. Gas chromatography GC FID and gas chromatography mass spectrometry GC-MS revealed that camphor 1, 19.0 %, E-caryophyllene 2, 9.3 %, eucalyptol 3, 6.8 %, germacrene D 6.7 %, and α-cadinol 6.5 % were the major chemical constituents of AA EO. However, when tested alone, compounds 1, 2, and 3 were inactive MIC > 1000 μg/mL against all the studied microorganisms.

β-Lapachone is a drug candidate in phase II clinical trials for treatment of solid tumors. The therapeutic efficacy of β-lapachone is closely related to its metabolism, since this o-naphthoquinone produces cytotoxic effect after intracellular bioreduction by reactive oxygen species formation. The aim of this study was to produce β-lapachone human blood phase I metabolites to evaluate their cytotoxic activities. The biotransformation of β-lapachone was performed using Mucor rouxii NRRL 1894 and Papulaspora immersa SS13. The metabolites were isolated and their chemical structures determined from spectrometric and spectroscopic data. Cell cytotoxicity assays were carried out with β-lapachone and its metabolites using the neoplastic cell line SKBR-3 derived from human breast cancer and normal human fibroblast cell line GM07492-A. Microbial transformation of β-lapachone by filamentous fungi resulted in the production of five metabolites identical to those found during human blood metabolism, a novel metabolite and a product stated before only in a synthetic procedure. The analysis of the results showed that β-lapachone metabolites were not cytotoxic for the neoplastic cell line SKBR-3 derived from human breast cancer and the normal human fibroblast cell line GM07492-A. The cytotoxic activity assay against the neoplastic cell line SKBR-3 revealed that the lowest half-maximal inhibitory concentration (IC50) values of these β-lapachone metabolites were 33- to 52-fold greater than IC50 values of β-lapachone. The cytotoxic activity of β-lapachone in vivo may be reduced due to its swift conversion in blood.

The saturated nitrogen-containing heterocyclic compounds include many drugs and compounds that may be used as synthons for the synthesis of other pharmacologically active substances. The need for new derivatives of saturated nitrogen-containing heterocycles for organic synthesis, biotechnology and the pharmaceutical industry, including optically active derivatives, has increased interest in microbial synthesis. This review provides an overview of microbial technologies that can be valuable to produce new derivatives of saturated nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-, regio- and enantioselectivity of microbial processes can be indispensable for the synthesis of new compounds. Microbial processes carried out with fungi, including Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum, Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many substrates efficiently. Among the biological activities of saturated nitrogen-containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive and anti-HIV activities; some derivatives are effective for the treatment and prevention of malaria and trypanosomiasis, and others are potent glycosidase inhibitors.

In the screening for biological active compounds, the biotransformation processes catalyzed by filamentous fungi are useful because they can provide information about the possible appearance of toxic metabolites after oral administration and also generate new leads. In this paper, biotransformation of lapachol (1) by three fungal strains, Mucor circinelloides NRRL3631, Botrytis cinerea UCA992 and Botrytis cinerea 2100, has been investigated for the first time. Lapachol (1) was biotransformed into avicequinone-A (2) by M. circinelloides, 3′-hydroxylapachol (3) by B. cinerea, and into dehydro-α-lapachone (4) by both fungi. All these compounds were evaluated for their cytotoxic activities. The metabolite 2 displayed non-selective cytotoxicity against tumor and normal cell lines, 3 did not show cytotoxicity against the same cells, while 4 showed higher cytotoxicity against cancer cell lines than lapachol (1). The transformation of 1 into harmless and reactive metabolites evidences the importance of the evaluation of drug metabolism in the drug discovery process. Antifungal potential of lapachol (1) and its metabolites 2 and 4 against B. cinerea has also been evaluated. Dehydro-α-lapachone (4) has been shown to be less toxic to fungal growth than lapachol (1), which indicates a detoxification mechanism of the phytopathogen.

In the natural products research, a valuable approach is the prospection of uncommon sources and unexplored habitat. Special attention has been given to endophytic fungi because of their ability to produce new and interesting secondary metabolites, which have several biological applications. The endophytes establish exclusive symbiotic relationships with plants and the metabolic interactions may support the synthesis of some similar valuables compounds. Among secondary metabolites, phenol-derived structures are responsible for several bioactivities such as antioxidant, cytotoxic, antimicrobial, among others. Phenolic compounds might be biosynthesized from the shikimate pathway. Although shikimic acid is a common precursor in plants, it is described as rare in microorganisms. To the best of our knowledge, this is the first review about phenolic compounds produced by endophytic fungi and a comparison has been made with those produced by the plant host. This review covers 124 phenolic secondary metabolites produced by endophytic fungi. Considering the data analyzed by us, only seven of such compounds were isolated from fungi and from their hosts. These observations claim for more attention to phenolic compounds produced by endophytic fungi with a view to understand the real importance of these compounds to endophytes survival.