Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF.

Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases catalyze various oxidative biotransformations. Due to their catalytic flexibility and high efficiency, Fe/αKG oxygenases have attracted keen attention for their application as biocatalysts. Here, we report the biochemical and structural characterizations of the unusually promiscuous and catalytically versatile Fe/αKG oxygenase SptF, involved in the biosynthesis of fungal meroterpenoid emervaridones. The in vitro analysis revealed that SptF catalyzes several continuous oxidation reactions, including hydroxylation, desaturation, epoxidation, and skeletal rearrangement. SptF exhibits extremely broad substrate specificity toward various meroterpenoids, and efficiently produced unique cyclopropane-ring-fused 5/3/5/5/6/6 and 5/3/6/6/6 scaffolds from terretonins. Moreover, SptF also hydroxylates steroids, including androsterone, testosterone, and progesterone, with different regiospecificities. Crystallographic and structure-based mutagenesis studies of SptF revealed the molecular basis of the enzyme reactions, and suggested that the malleability of the loop region contributes to the remarkable substrate promiscuity. SptF exhibits great potential as a promising biocatalyst for oxidation reactions.

Phytochemical Profile and Antioxidant Activity of Nigella sativa L Growing in Morocco.

BACKGROUND: Nigella sativa L (NS) is a powerful antioxidant and medicinal plant with many therapeutic applications particularly in traditional medicine for respiratory, gastrointestinal, rheumatic, and inflammatory disorders, as well as cancer. OBJECTIVE: The aim of this study is to extract the active ingredients from the Moroccan Nigella sativa L and determine its antioxidant properties. We hypothesize that the separation of the compounds from Nigella sativa L has either a positive or negative effect on antioxidants. To study this, we explored different methods to simultaneously extract and separate compounds from Nigella sativa L and performed antioxidant tests (ß-carotene and DPPH) for all collected fractions. METHODS: Nigella sativa L was hot-extracted by Soxhlet and mother extracts and was separated using silica column chromatography with adequate eluents. Qualitative phytochemical tests to determine the chemical families in Nigella sativa L seeds were performed on the fractions. They were also identified and characterized by GC-MS and HPLC-DAD. Then, antioxidant activity was examined by ß-carotene bleaching and DPPH radical scavenger tests. Results and Conclusion. The mother extract hexane FH generated eight different fractions (SH1-8) and the acetone extract FA generated 11 fractions (SA1-11). The FH fractions had a high percentage of fatty acids, and the FA fractions had some interesting polyphenols derivative compounds. Phytochemical screening revealed secondary metabolites such as polyphenols flavonoids, alkaloids, steroids, terpenes coumarins, tannins, and saponins. We found that only two solvents (hexane, acetone) of different polarities could easily extract and simultaneously separate the components of Nigella sativa L. The antioxidant fractions that we collected had close activity to reference compounds but were more active than the corresponding mother extracts. Moreover, several IC50 values of fractions from acetone extract were better than those from hexane. Therefore, the antioxidant activity of Nigella sativa L is more attributed to flavonoids and polyphenols than fatty acids. In summary, the separation of hexane extract presents a more pronounced positive effect for antioxidant tests than acetone extract.

Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity.

In recent years, many studies have shown that phytochemicals exert their antibacterial activity through different mechanisms of action, such as damage to the bacterial membrane and suppression of virulence factors, including inhibition of the activity of enzymes and toxins, and bacterial biofilm formation. In this review, we summarise data from the available literature regarding the antibacterial effects of the main phytochemicals belonging to different chemical classes, alkaloids, sulfur-containing phytochemicals, terpenoids, and polyphenols. Some phytochemicals, besides having direct antimicrobial activity, showed an in vitro synergistic effect when tested in combination with conventional antibiotics, modifying antibiotic resistance. Review of the literature showed that phytochemicals represent a possible source of effective, cheap and safe antimicrobial agents, though much work must still be carried out, especially in in vivo conditions to ensure the selection of effective antimicrobial substances with low side and adverse effects.

Chemical constituents of Pseudobrickellia brasiliensis leaves(Spreng. ) R.M. King & H. Rob. (Asteraceae) / Constituintes químicos das folhas de Pseudobrickellia brasiliensis (Spreng. ) R.M. King & H. Rob. (Asteraceae).

ABSTRACT Pseudobrickelliabrasiliensisis aspecies endemic toBrazil, popularlyknown as “arnica”/ “arnica-do-campo”/ “arnica-do-mato” and used for itsanalgesicand anti-inflammatoryproperties. The objective of this research was thephytochemical studyof the essential oilandhexaneandethyl acetateextracts of the leaves of this species. The essential oilwasextracted byhydrodistillation using a Clevengerapparatusand was analyzed byGC/MS, 25components were identified, with a predominance ofmonoterpenes. The extractswere subjected toclassicalchromatographyand the fractionswere analyzed byGC/MS, 1D 1H-NMR, 13C-NMR and 13C-NMR-DEPT 135.α-amyrin, α-amyrin acetate, β-amyrin, β-amyrin acetate, lupeol, lupeolacetate, pseudotaraxasterol andtaraxasterol (triterpenes), andkaurenoicacid (diterpene) were identified.Theseterpenesarechemo-taxonomicallyrelated to theEupatorieaetribe(Asteraceae) and may be responsible for the anti-inflammatory activity attributed to the plant.

RESUMO Pseudobrickellia brasiliensis é uma espécie endêmica do Brasil, popularmente conhecida como “arnica”/ “arnica-do-campo”/ “arnica-do-mato” e usada por suas propriedades analgésica e antiinflamatória. O objetivo do trabalho foi o estudo fitoquímico do óleo essencial e dos extratos hexânico e em acetato de etila das folhas dessa espécie. O óleo essencial foi extraído por hidrodestilação em aparato de Clevenger e foi analisado por CG/EM, sendo identificados 25 componentes, com predomínio de monoterpenos. Os extratos foram submetidos a cromatografia clássica, e as frações foram analisadas por CG/EM, 1D 1H-RMN, 13C-RMN e 13C-RMN-DEPT 135. Foram identificados α-amirina, acetato de α-amirina, β-amirina, acetato de β-amirina, lupeol, acetato de lupeol, pseudotaraxasterol e taraxasterol (triterpenos) e o ácido caurenóico (diterpeno). Estes terpenos estão quimiotaxonomicamente relacionados a tribo Eupatorieae (Asteraceae) e podem ser responsáveis pela atividade antiinflamatória atribuída a planta.

Terpenes from the soft corals Litophyton arboreum and Sarcophyton ehrenbergi.

The new cembrane diterpene (3E,11E)-cembra-3,8(19),11,15-tetraene-7alpha-ol (1), nephthenol (2), and all-trans-peridinin (3) have been isolated from the soft coral Litophyton arboreum. The tetraterpene 3, (+)-7,8-epoxy-7,8-dihydrocembrene C (4), emblide (5), sarcophytoxide (6), sarcoglaucol-16-one (7), guajacophine (8), and 1,4-peroxymuurol-5-ene (9) have been obtained from the soft coral Sarcophyton ehrenbergi. The compounds were characterized primarily by NMR spectroscopy. Some of the terpenes were tested for their antiproliferative activity against the cell lines HUVEC and K-562 and for cytotoxicity against the cell line HeLa, and they showed moderate activities.

Molecular basis of the anti-inflammatory effects of terpenoids.

Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, anti-inflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-kappaB) activation. NF-kappaB plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-kappaB expression is a characteristic phenomenon in several inflammatory diseases and NF-kappaB has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-kappaB. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.

Composition, irregular terpenoids, chemical variability and antibacterial activity of the essential oil from Santolina corsica Jordan et Fourr.

A detailed analysis of Santolina corsica essential oil was carried out by combination of GC (RI), GC-MS and 13C NMR spectroscopy. After fractionation by column chromatography, 50 components were identified, accounting for 88.2% of the total amount of the oil. The chemical composition was dominated by monoterpene hydrocarbons, myrcene (34.6%), santolina triene (13.5%) and beta-phellandrene (11.7%). Beside the main compounds, we noted the occurrence of irregular mono and sesquiterpenes belonging to five families: santolinane, artemisane, chrysanthemane, lavandulane and sesquilavandulane. Three compounds, lyratyl butyrate, isolyratone and epi-isolyratol were isolated and their structure elucidated by 2D NMR. Antibacterial activity was tested against six bacteria strains. The essential oil was effective against Staphylococcus aureus and C. jejuni. Lyratol was identified as main responsive of the antibacterial activity. The content of lyratol was measured in 33 oil samples isolated from individual plants.

Chromenes from the brown alga Sargassum siliquastrum.

Sargachromanols A-P (1-16), sixteen new meroterpenoids of the chromene class, were isolated from the brown alga Sargassum siliquastrum collected from Jaeju Island, Korea. On the basis of the combined results of spectral and chemical analyses, the structures of the polyprenyl portions of these chromanol-containing compounds were determined to be linear triprenyls (1 and 2) and tetraprenyls (3-11), while others were the corresponding rearranged (12-15) and cyclized (16) tetraprenyls, respectively. The new compounds exhibited significant antioxidant activity in the DPPH assay. Compounds 7 and 15 also showed inhibitory activity toward butylcholine esterase.