Natural Products and Bioprospecting最新文献

A chemical investigation of Streptomyces sp. GZWMJZ-662, an endophytic actinomycete isolated from Houttuynia cordata Thunb., has yielded eleven bohemamine dimers (1–11). Notably, the newly identified dibohemamines I–O (1–7) have not been previously reported. Their structures were elucidated through detailed spectroscopic analysis, encompassing high-resolution electrospray ionization mass, nuclear magnetic resonance, infrared radiation, ultraviolet–visible, and electronic circular dichroism spectroscopy. Dibohemamine I (1) exhibited selective cytotoxic effects against the cancer cell lines 786-O and GBC-SD among the 18 cell lines evaluated, with the half-inhibitory concentration values of 3.24 ± 0.20 and 7.36 ± 0.41 μM, respectively.

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Teucrifarides A–D (1–4), four previously unreported neo-clerodane-type diterpenoids, combined with sixteen known analogs (5–20), were purified from Teucrium quadrifarium. The absolute forma of compounds 1–4 were determined via spectroscopic and ECD calculation methods, together with X-ray crystallography experiments. Among them, compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo [5.3.2.0^1,6]undecane skeleton. Meanwhile, 2 incorporated a 6,20-epoxy ring with a novel 12-oxatricyclo [6.2.2.0^2,7]undecane skeleton. Compounds 1 and 12 exhibited significant inhibitory effects against HT-22 cells ferroptosis induced by RSL3, with EC₅₀ values of 11.8 ± 1.0 μM, and 4.52 ± 1.24 μM, respectively. Moreover, ROS accumulation in HT22 cells treated with compound 1 was also observed.

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The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis. These compounds have antiproliferative activity against fungal pathogens and mammalian cancer cell lines. Analysis of E. gracilis extracts revealed that the algae produce not only the euglenatides, but also a corresponding family of analogs that have the same molecular weights as the euglenatides, but are lacking the characteristic triene chromophore. In comparison to the euglenatides, the activity of these analogs is greatly reduced in a mammalian cytotoxicity assay, indicating that the triene is critical to the biological activity of the euglenatides.

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Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules. Prepared through direct derivatization of natural extracts, they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs. Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent, and their α-glucosidase inhibition properties were compared. For the most bioactive mixture, a chemically modified propolis extract, enzyme inhibition increased 22 times due to the reaction sequence. Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin. The inhibitor results from the action of the two reagents used on four common functional groups present in natural products (carbonyl, phenol, aromatic carbon, and a double bond). The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one, as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material, all within a complex mixture of natural products. Overall, these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.

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In the twenty-first century, we have witnessed multiple coronavirus pandemics. Despite declining SARS-CoV-2 cases, continued research remains vital. We report the discovery of sydowiol B, a natural product, as a dual inhibitor of SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro). Sydowiol B interacts with the nano-channel at the Mpro dimer interface and the PLpro active site. Molecular dynamics simulations suggest that sydowiol B inhibits Mpro by limiting active site expansion rather than inducing collapse. Furthermore, sydowiol B binding may amplify the fluctuation of two loops coordinating with the structural Zn²⁺ in PLpro, displacing Zn²⁺ from the zinc finger domain to the S2 helix. Sydowiol B and its analogue, violaceol I, exhibit broad-spectrum antiviral activity against homologous coronaviruses. Given the conservation of Mpro and PLpro, sydowiol B and violaceol I are promising leads for designing and developing anti-coronavirus therapies.

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The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier, providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach. This study explores the dynamic intersection of phytochemistry and forensic science, highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites, serve as distinctive markers for forensic investigations. By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography (UHPLC) and High-Resolution Mass Spectrometry (HRMS), the detection and quantification of plant-derived are made more accurate in forensic contexts. Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings. The challenges, potential, and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed. This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses, offering new insights into the complex stories embedded in plant toxins.

Fifteen novel carbazole alkaloids, euchrestifolines A–O (1–15), were obtained from Murraya euchrestifolia. Their structures were elucidated by spectroscopic analysis, Mosher’s ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A–C (1–3) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D–F (4–6) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (7) features a unique benzopyranocarbazole skeleton. More importantly, these compounds exhibited significant anti-ferroptotic activity, along with inhibitory effects of nitric oxide (NO) production and notable cytotoxicity. This study marks the first disclosure of carbazole's inhibitory effects against ferroptosis, and the EC₅₀ values of some carbazoles ranging from 0.04 to 1 μM, substantially lower than the positive control, ferrostatin-1. In sum, this research not only enhances our understanding of carbazole alkaloids but also opens new avenues for the discovery of ferroptosis-related leading compounds.

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Angelica L. has attracted global interest for its traditional medicinal uses and commercial values. However, few studies have focused on the metabolomic differences among the Angelica species. In this study, widely targeted metabolomics based on gas chromatography-tandem mass spectrometry was employed to analyze the metabolomes of four Angelica species (Angelica sinensis (Oliv.) Diels (A. sinensis), Angelica biserrata (R.H.Shan & Yuan) C.Q.Yuan & R.H.Shan (A. biserrata), Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (A. dahurica) and Angelica keiskei Koidz. (A. keiskei)). A total of 698 volatile metabolites were identified and classified into fifteen different categories. The metabolomic analysis indicated that 7-hydroxycoumarin and Z-ligustilide accumulated at significantly higher levels in A. sinensis, whereas bornyl acetate showed the opposite pattern. Furthermore, a high correspondence between the dendrogram of metabolite contents and phylogenetic positions of the four species. This study provides a comprehensive biochemical map for the exploitation, application and development of the Angelica species as medicinal plants or health-related dietary supplements.

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The Plectranthinae clade, which includes genera such as Plectranthus, Ocimum, and Aeollanthus, is well known for its diverse array of diterpenoids. While numerous studies have deepened the understanding of diterpene diversity across the clade, Aeollanthus species remain underexplored, with only two studies focusing on their diterpene profiles. The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq. reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues. Interestingly, the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra. These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.

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Thirty-six structurally diverse sesquiterpenoids, including caryolanes (1–12), germacranes (13–16), isodaucane (17), cadinanes (18–22), epicubenols (23, 24), oplopanane (25), pallenanes (26, 27), and eudesmanes (28–36), were isolated from the fermentation broth of Streptomyces fulvorobeus derived from Elephas maximus feces. Pallenane is a kind of rarely reported sesquiterpene with a distinctive C5/C3 bicyclic skeleton and was firstly found from microbial source. The structures of fifteen new compounds (1–4, 13–15, 17, 18, 22, 23, 25–28) were established through detailed spectroscopic data analysis, which included data from experimental and calculated ECD spectra as well as Mosher’s reagent derivative method. Compound 34 exhibited moderate antifungal activity against Cryptococcus neoformans and Cryptococcus gattii with MIC values of 50 μg/mL. It effectively inhibited biofilm formation and destroyed the preformed biofilm, as well as hindered the adhesion of Cryptococcus species. The current work would enrich the chemical diversity of sesquiterpenoid family.

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