Natural Products and Bioprospecting最新文献

Tuberculosis (TB) is a leading infectious disease killer and one of the major causes of deaths worldwide. Although TB is a curable and preventable disease, in 2023, approximately 10.8 million people fell ill with TB and there were an estimated 1.25 million of deaths worldwide. Despite some research progress for new drug candidates, drug repurposing, and new regimens, there is still an urgent need for the new medicins to treat TB, especially due to the growing cases of multidrug and extensively drug-resistant (MDR/XDR) strains. Drug resistance is a challenging obstacle to TB care and prevention globally, making TB harder and longer to treat, often with poorer outcomes for patients. The Actinomycetota encompass Gram-positive bacteria that produce a milieu of bioactive metabolites, including antibiotics, antiproliferative drugs, immunosuppressive agents, and other important medical molecules. Actinomycetota have a special place in the therapeutic arsenal to fight TB, as rifamycins, aminoglycosides, and cycloserine are derived from Streptomyces species, one of the most important genera in this phylum. Furthermore, hundreds of antimycobacterial metabolites have been isolated from Actinomycetota and can serve as effective drugs or useful agents for the discovery of new lead compounds to combat TB. The present review covers more than 171 isolated substances as potential antimycobacterial agents discovered between the years 1972 to 2024. Among the most potent compounds, with MIC in the submicromolar range, steffimycins, ilamycins/rufomycins, nosiheptide, actinomycins, lassomycin and boromycin are the most promising compounds. These compounds represent highly promising candidates for development of new antitubercular drugs. Additionally, some of these substances also demonstrated activity against resistant Mycobacterium tuberculosis (Mtb) strains, which is particularly relevant given the difficulty of treating MDR and XDR strains. Thus, actinobacteria have played and continue to play an important role in fight TB, remaining a promising source of antibiotic metabolites. Their unique metabolic diversity enables the production of metabolites with innovative mechanisms of action, making them a strategic reservoir for discovering therapies against untreatable forms of the disease.

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Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4, bearing a 4-bromobenzoylmethyl substituent at the N-1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC₅₀ values of 1.40–1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC₅₀ of 9.24 ± 0.20 μM and exerts effective inhibition of the phosphorylation of key PI3K/Akt/mTOR signaling proteins. Besides, a4 significantly downregulates the expression of the immune checkpoint protein PD-L1, indicating its potential to activate tumor immunity. These findings demonstrate that tanshinone I-pyridinium salt derivative a4 is a novel PI3Kα inhibitor, providing a solid foundation for further development of antitumor agents.

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The extraction of anticancer agents from medicinal plants represents a highly promising research frontier. Ginkgetin, a natural biflavone, is one of the effective pharmacological components of Ginkgo biloba leaves (GBLs). This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity. Additionally, ginkgetin synergizes with chemotherapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects. These compelling findings underscore Ginkgetin's potential as a promising candidate for novel anti-cancer therapeutics. Therefore, this review systematically summarizes the remarkable anticancer effects of ginkgetin and elucidates its multifaceted anticancer mechanisms, including inducing cell cycle arrest, triggering programmed cell death, and preventing invasion and angiogenesis. From a molecular mechanism perspective, ginkgetin exerts anti-cancer activity by modulating critical signaling pathways (e.g. JAK/STAT, Wnt/β-catenin, AKT/GSK-3β, MAPKs, and estrogen receptor pathways) and regulating microRNA expression levels. Furthermore, target identification, research limitations, future directions, and application prospects are comprehensively outlined, aiming to facilitate the clinical translation of ginkgetin.

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The trace element selenium is essential for human nutrition but is distributed unevenly in soils worldwide with extensive selenium-deficient regions and selenium-enriched (seleniferous) areas. Neptunia amplexicaulis is one of the strongest selenium hyperaccumulator plants known and native to Australian seleniferous soils. Research in the genetic background of the selenium accumulation and tolerance mechanisms of this species lacks biotechnological and molecular tools for functional genetics. Therefore, this study aimed to develop a de novo shoot regeneration protocol for N. amplexicaulis and validate an selenium accumulation test system. Callus was induced on root and hypocotyl explants excised from 5-day old seedlings and cultured on an adjusted MS medium (SIM9) containing 4.5 µM Thidiazuron (TDZ) for two weeks in darkness. After this period, the TDZ concentration was reduced to 0.45 µM, and the explants were transferred to light conditions. In addition, seedlings of N. amplexicaulis, N. heliophila and Medicago truncatula were placed on vertical MS agar plates containing 1.5 mM (standard) or 0.1 mM (low) magnesium sulphate with 0, 30, 90 µM sodium selenate. Initial shoot differentiation was observed 6 weeks after culture initiation. This regeneration response was successfully repeated in a second experiment. The outgrow of the shoot buds into complete shoots was not yet achieved but requires additional media optimization. Additionally, spontaneous shoot regeneration from a root was observed, highlighting potential for further studies. In vitro grown seedlings demonstrated efficient, selective selenium uptake in N. amplexicaulis and identified M. truncatula as a secondary selenium accumulator with selenium concentrations of > 300 µg Se g⁻¹ DM. This project presents the first protocol for inducing early stages of development of indirect shoot organogenesis in N. amplexicaulis from hypocotyl and root explants as prerequisite for genetic transformation, though completing the regeneration cycle remains challenging. Neptunia amplexicaulis hyperaccumulates selenium also under in vitro conditions.

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This study focuses on the peptaibiome produced by different species of Trichoderma belonging to clade Viride: T. koningii SZMC 28387 (CBS 979.70), T. cf. strigosellum SZMC 28007 (TUCIM 4886/IQ 191), T. cf. dorothopsis SZMC 28390 (TUCIM 416/TUB F-597), T. cf. strigosellum SZMC 28391 (TUCIM 423/DAOM 230018), T. atroviride SZMC 28748 (IMI 206040), T. hamatum SZMC 28747 (TUCIM 2730) and T. cf. dorothopsis SZMC 28005 (TUCIM 4882/IQ 11). We were able to identify new compounds with similarity to already known groups of peptaibiotics, as well as completely newly discovered compounds using high-performance liquid chromatography (HPLC) -mass spectrometry (MS). From the 367 peptaibiotics identified, 216 are peptaibols and 111 are lipopeptaibols. Out of all peptaibols, 55 are previously known, while 161 are newly discovered. The new peptaibol subgroups Strigosellin A, B and Dorothopsin A, B are introduced. Furthermore, besides 38 previously known lipopeptaibols, 73 new lipopeptaibol sequences, named Lipostrigosellins and Lipohamatins are also reported. In addition, 41 peptaibol-like compounds with unusual C-terminus were also found. Out of the 7 strains examined, 5 produced both peptaibols and lipopeptaibols, while 2 only peptaibols. The well-known compound, Trikoningin KA V (TRK-V) also produced by T. koningii SZMC 28387 (CBS 979.70), was studied for its folding dynamics using accelerated molecular dynamics simulations (aMD) for understanding the plausible three-dimensional structures adopted by these peptaibols of clade Viride. We observed a propensity to form kinked, right-handed helical structures when simulated in an aqueous environment.

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The Meliaceae family, widely distributed in tropical and subtropical regions, has been traditionally used for medicinal purposes, particularly in treating infections and inflammatory diseases. The objective of this study is to provide a comprehensive account of the nitrogen-containing secondary metabolites and their biological activities that have been isolated from the Meliaceae family between the years 1979 and 2024. Studies on nitrogen-containing compounds of the Meliaceae family were collected and analyzed using data from SciFinder, PubMed, Google Scholar, Scopus and World Flora Online. Over the course of more than four decades, numerous studies have been conducted on a variety of plant parts, including twigs, stems, barks, roots, fruits, seeds, and leaves. These studies have identified approximately 326 compounds belonging to diverse chemical groups, such as alkaloids, limonoids, triterpenoids, and nitrogen-containing flavaglines being the largest group of natural products, comprising 118 compounds (36.2%). Several compounds have been evaluated for insecticidal, anti-inflammatory, molluscicide, antibacterial, antimalarial, tyrosinase inhibition, osteoclast differentiation inhibition, and α-glucosidase inhibition activity. The systematic classification and analysis of these compounds provide insights into their biosynthesis and bioactivities, paving the way for future drug development.

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Seven previously undescribed polycyclic meroterpenoids talarines K–Q (1–7), along with five known ones (8–12), were isolated from desert-derived fungi Talaromyces sp. HMT-8. The structure of the novel compounds were elucidated using spectroscopic methods, including electronic circular dichroism (ECD), HRESIMS and nuclear magnetic resonance (NMR) spectroscopy. Among the isolated meroterpenoids, compounds 3, 5, and 7 exhibited rare chlorine substitution patterns. Halogenation, particularly chlorination, is uncommon in natural meroterpenoids and implies the involvement of halogenase enzymes during biosynthesis. Compounds 1–12 were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Compounds 1–4 and 12 exhibited inhibitory activity against PTP1B with IC₅₀ values ranging from 1.74 to 17.60 μM. Among them, compounds 2 and 12 displayed significant inhibitory effects with an IC₅₀ value of 1.74 and 3.03 μM, respectively. Furthermore, Molecular docking analysis revealed that compounds 2 and 12 bind tightly to the catalytic site of PTP1B, forming key hydrogen bonding and hydrophobic interactions. Enzyme kinetics studies further demonstrated that both compounds act as competitive inhibitor.

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Purpose

The purpose of this study was to phytochemically profile Himantoglossum robertianum leaves. In fact, despite its wide distribution and its use in traditional medicine, this orchid is still understudied and little is known about its phytochemicals.

Methods

The analyses were performed by ¹H NMR fingerprinting, elucidated by further 2D NMR and UHPLC-MS experiments. Both primary and secondary metabolites were qualified and quantified. The study was carried out comparing six natural populations by metabolomics approach, allowing further considerations on the influence of the environment on the concentration of metabolites.

Results

This work brings to light a surprising phytochemical parallel between H. robertianum and the medicinal orchid Gastrodia elata. In fact, the most abundant specialized metabolites resulted: gastrodigenin, gastrodin, bis(4-hydroxybenzyl)ether, parishin A, parishin C, and parishin E. Interestingly, these metabolites are all known for their potential in the treatment of neurological disorders and are, indeed, the active principles of Gastrodia elata, an important orchid used in Traditional Chinese Medicine. The active metabolites were present in all the natural populations, where only slight variations in their concentration were revealed.

Conclusion

Mapping the metabolome of H. robertianum leaves has provided new insights into the study of orchids, including diagnostic signals for rapid identification of gastrodigenin-like compounds directly from the ¹H NMR profile of a crude extract. From a bioprospecting perspective, finding active metabolites in leaves makes the plant source more valuable than the perennial hypogeal organs that are usually the herbal drug of orchids (i.e. G. elata).

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