Chemovariation and antibacterial activity of extracts and isolated compounds from species of Ixora and Greenea (Ixoroideae, Rubiaceae)

Background A large number of secondary metabolites can be obtained from plants used for traditional medicine in two related genera (Ixora and Greenea) in the subfamily Ixoroideae (Rubiaceae), but there are only a few detailed studies on their bioactivities. Therefore, the main goals of this study were to determine the antibacterial activities of lipophilic extracts from plants of some Ixora and Greenea species native to Thailand, and to isolate some pure compounds from those extracts. Moreover, we compared the occurrence of compounds in different plant parts of samples from different habitats to better understand their variation. Methods A total of 56 lipophilic extracts were obtained from the leaves, stem bark, and root bark of eight Ixora and two Greenea species collected at various locations in Thailand. Isolated compounds were identified using nuclear magnetic resonance. Antimicrobial activities were evaluated against four Gram-positive and nine Gram-negative human pathogenic bacterial strains. Results Extracts from I. javanica, I. nigricans, I. brunonis, and G. montana, along with isolated scopoletin, exhibited antibacterial activities against Gram-positive methicillin-resistant Staphylococcus aureus ATCC 43300, with minimum inhibitory concentration values ranging from 64 to 256 µg/mL. The occurrence of scopoletin, isofraxidin, and geniposidic acid in lipophilic extracts showed some variation among different plant parts and species. Conclusions Lipophilic extracts of Ixora and Greenea species have the potential to be developed as anti-Gram-positive agents, in particular to counter infections of methicillin-resistant S. aureus strains. The chemical profiles showed differences between floristic regions but similarity within the same plant parts

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Energie-Umweltmanagemen

Highly Aromatic Flavan-3-ol Derivatives from Palaeotropical <i>Artocarpus lacucha</i> Buch.-Ham Possess Radical Scavenging and Antiproliferative Properties

Phytochemical investigation of leaves and stembark of Artocarpus lacucha collected in Thailand resulted in three yet undescribed isomeric flavan-3-ol derivatives (1–3), the four known compounds gambircatechol (4), (+)-catechin (5), (+)-afzelechin (6) and the stilbene oxyresveratrol (7). Compounds 1 to 3 feature 6/6/5/6/5/6 core structures. All structures were deduced by NMR and MS, while density functional theory (DFT) calculations on B3LYP theory level were performed of compounds 1 to 3 to support the stereochemistry in positions 2 and 3 in the C-ring. Possible biosynthetic pathways leading to 4 are discussed. The DPPH assay revealed high radical scavenging activities for 1 (EC50 = 9.4 ± 1.0 µmol mL−1), 2 (12.2 ± 1.1), 3 (10.0 ± 1.5) and 4 (19.0 ± 2.6), remarkably lower than ascorbic acid (EC50 = 34.9) and α-tocopherol (EC50 = 48.6). A cytotoxicity assay revealed moderate but consistent antiproliferative properties of 1 in CH1/PA-1 (ovarian teratocarcinoma) and SW480 (colon carcinoma) cells, with IC50 values of 25 ± 6 and 34 ± 4 µM, respectively, whereas effects in A549 (non-small cell lung cancer) cells were rather negligible. The performed DCFH-DA assay of 1 in the former cell lines confirmed potent antioxidative effects even in the cellular environment

Phytochemistry Meets Geochemistry&mdash;Blumenol C Sulfate: A New Megastigmane Sulfate from Palicourea&nbsp;luxurians (Rubiaceae: Palicoureeae)

There is a previously neglected influence of geochemical conditions on plant phytochemistry. In particular, high concentrations of dissolved salts can affect their biosynthesis of natural products. Detoxification is most likely an important aspect for the plant, but additional natural products can also give it an expanded range of bioactivities. During the phytochemical analysis a Palicourea luxurians plant collected in a sulfate-rich environment (near the R&iacute;o Sucio, Costa Rica) showed an interesting natural product in this regard. The structure of this compound was determined using spectroscopic and computational methods (NMR, MS, UV, IR, CD, optical rotation, quantum chemical calculations) and resulted in a megastigmane sulfate ester possessing a &beta;-ionone core structure, namely blumenol C sulfate (1, C13H22O5S). The levels of sulfur and sulfate ions in the leaves of the plant were determined using elemental analysis and compared to the corresponding levels in comparable plant leaves from a less sulfate-rich environments. The analyses show the leaves from which we isolated blumenol C sulfate (1) to contain 35% more sulfur and 80% more sulfate than the other samples. Antimicrobial and antioxidant activities of compound 1 were tested against Escherichia coli, E. coli ampR and Bacillus subtilis as well as measured using complementary in vitro FRAP and ATBS assays, respectively. These bioactivities are comparable to those determined for structurally related megastigmanes. The sulfur and sulfate content of the plant leaves from the sulfate-rich environment was significantly higher than that of the other plants. Against this background of salt stress, we discuss a possible biosynthesis of blumenol C sulfate (1). Furthermore, there appears to be no benefit for the plant in terms of extended bioactivities. Hence, the formation of blumenol C sulfate (1) probably primarily serves the plant detoxification process

Yellow Twig (<i>Nauclea</i> <i>orientalis</i>) from Thailand: Strictosamide as the Key Alkaloid of This Plant Species

Comprehensive phytochemical examination from different perspectives using preparative and analytical chromatographic techniques combined with spectroscopic/spectrometric methods of the so-called “yellow twig” Nauclea orientalis (L.) L. (Rubiaceae) led to the identification of 13 tryptamine-derived (=monoterpene-indole) alkaloids. The identified alkaloids comprise strictosamide and four of its glucosidic derivatives, three oxindole derivatives, and five yellow-colored angustine-type aglycones. Qualitative and quantitative HPLC analyses showed the enrichment of strictosamide in all studied organs. Based on these results, we performed metabolomic analyses of monoterpene-indole alkaloids and made a 1H NMR in vitro monitoring of enzymatic deglucosylation of strictosamide. A comparison of the stability of strictosamide and its enantiomer vincoside lactam by theoretical calculations was also performed revealing a slightly higher stability of vincoside lactam. Additionally, we conducted two different anti-feedant assays of strictosamide using larvae of the polyphageous moth Spodoptera littoralis Boisduval. The obtained results indicate that generally two different biosynthetic pathways are most likely responsible for the overall alkaloid composition in this plant. Strictosamide is the key compound in the broader pathway and most likely the source of the identified angustine-type aglycones, which may contribute significantly to the yellow color of the wood. Its cross-organ accumulation makes it likely that strictosamide is not only important as a reservoir for the further biosynthesis, but also acts in the plants’ defense strategy

Tabernabovines A–C: Three Monoterpenoid Indole Alkaloids from the Leaves of Tabernaemontana bovina

Three monoterpenoid indole alkaloids (MIAs), tabernabovines A–C (1–3), were isolated from Tabernaemontana bovina. They were elucidated by spectroscopic data and computational calculations. Unlike precursors of MIAs, strictosidine and alstrostine A, alkaloid 1 consists of tryptamine and secologanin in a 2:1 ratio. Alkaloid 2 is a cage compound, and 3 possesses a bridged ring. Tabernabovine A exhibited inhibitory activity against NO production with IC50 44.1 μM compared to l-NMMA with IC50 of 48.6 μM

MAPkinases regulate secondary metabolism, sexual development and light dependent cellulase regulation in Trichoderma reesei

Abstract The filamentous fungus Trichoderma reesei is a prolific producer of plant cell wall degrading enzymes, which are regulated in response to diverse environmental signals for optimal adaptation, but also produces a wide array of secondary metabolites. Available carbon source and light are the strongest cues currently known to impact secreted enzyme levels and an interplay with regulation of secondary metabolism became increasingly obvious in recent years. While cellulase regulation is already known to be modulated by different mitogen activated protein kinase (MAPK) pathways, the relevance of the light signal, which is transmitted by this pathway in other fungi as well, is still unknown in T. reesei as are interconnections to secondary metabolism and chemical communication under mating conditions. Here we show that MAPkinases differentially influence cellulase regulation in light and darkness and that the Hog1 homologue TMK3, but not TMK1 or TMK2 are required for the chemotropic response to glucose in T. reesei. Additionally, MAPkinases regulate production of specific secondary metabolites including trichodimerol and bisorbibutenolid, a bioactive compound with cytostatic effect on cancer cells and deterrent effect on larvae, under conditions facilitating mating, which reflects a defect in chemical communication. Strains lacking either of the MAPkinases become female sterile, indicating the conservation of the role of MAPkinases in sexual fertility also in T. reesei. In summary, our findings substantiate the previously detected interconnection of cellulase regulation with regulation of secondary metabolism as well as the involvement of MAPkinases in light dependent gene regulation of cellulase and secondary metabolite genes in fungi

Two Novel <i>Iboga</i>-Type and an Oxindole Glucuronide Alkaloid from <i>Tabernaemontana peduncularis</i> Disclose Related Biosynthetic Pathways to <i>Tabernaemontana divaricata</i>

Phytochemical investigation of the two Tabernaemontana species (Apocynaceae) T. peduncularis Wall. and T. divaricata (L.) R.Br. ex Roem. & Schult. indicated closely related biosynthetic pathways leading to lipophilic and hydrophilic alkaloids. In total, 18 specialized metabolites comprising indole-derived alkaloid aglycones, three oxindole-derived alkaloid glycosides, and two iridoid glucosides could be identified in the studied species. Among the alkaloids, the two Iboga-type alkaloids 3,7-coronaridine isoindolenine, coronaridine 3,4-iminium and a javaniside derivative bearing a glucuronic acid, named javanuronic acid, could be described by spectroscopic and spectrometric methods for the first time. A docking experiment using alpha-fold was performed to generate a protein model of the enzyme 7-deoxyloganetic acid glucosyl transferase. Performed bioassays exhibited a growth reduction of neonate Spodoptera littoralis larvae and reduced cell viability of HepG2 cells of the extracts containing Iboga alkaloids, whilst the javaniside derivatives containing hydrophilic fraction did not show any effects. These findings indicate a high flexibility in the formation of bioactive indole alkaloid aglycones by Tabernaemontana species and also evidence similar accumulation trends in both species as well as indicate that biosynthetic routes leading to oxindole alkaloids like javanisides are more widespread than reported. Furthermore, the incorporation of the three novel compounds into potential biosynthetic pathways is discussed

Boerelasins A–D, Four Unprecedented Cytochalasins from the Endophytic Fungus Boeremia Exigua

Four undescribed cytochalasins (1–4) were isolated from the endophytic fungus Boeremia exigua. Structurally, boerelasin A (1) represents the first example of a cytochalasin with a rare 5/5 bicyclic carbon core. Boerelasin B (2) possesses an unprecedented 5/6/5/6/8 pentacyclic ring system. Boerelasin C (3), a derivative from the common biosynthetic intermediate to 1, is a macrocyclic ring-opening cytochalasin, and boerelasin D (4) contains an uncommon six-carbon alkyl acid side chain. The structures were elucidated based on spectroscopic methods, electronic circular dichroism, spin–spin coupling constants, and calculated nuclear magnetic resonance with DP4+ analysis. These compounds exhibited significant cytotoxicity against the tumor cells