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Chinese Journal of Natural Medicines Sep 2021Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring... (Review)
Review
Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries. Biosynthesis of various LRDs has been extensively studied, leading to characterization of a large number of new biosynthetic enzymes. The biosynthetic pathways of important LRDs and the relevant enzymes (especially diterpene synthases and cytochrome P450 enzymes) were summarized in this review.
Topics: Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Diterpenes; Diterpenes, Kaurane; Plants
PubMed: 34561077
DOI: 10.1016/S1875-5364(21)60100-0 -
Plant Physiology and Biochemistry : PPB Jan 2023Species of the genus Coffea accumulate diterpenes of the ent-kaurane family in the endosperm of their seeds, of which cafestol and kahweol are the most abundant. The...
Species of the genus Coffea accumulate diterpenes of the ent-kaurane family in the endosperm of their seeds, of which cafestol and kahweol are the most abundant. The diterpenes are mainly stored in esterified form with fatty acids, mostly palmitate. In contrast to the numerous studies on their effects on human health and therapeutic applications, nothing was previously known about their biological and ecological role in planta. The antifungal and anti-insect activities of cafestol and cafestol palmitate were thus investigated in this study. Cafestol significantly affected the mycelial growth of five of the six phytopathogenic fungi tested. It also greatly reduced the percentage of pupation of larvae and the pupae and adult masses of one of the two fruit flies tested. By contrast, cafestol palmitate had no significant effect against any of the fungi and insects studied. Using confocal imaging and oil body isolation and analysis, we showed that diterpenes are localized in endosperm oil bodies, suggesting that esterification with fatty acids enables the accumulation of large amounts of diterpenes in a non-toxic form. Diterpene measurements in all organs of seedlings recovered from whole seed germination or embryos isolated from the endosperm showed that diterpenes are transferred from the endosperm to the cotyledons during seedling growth and then distributed to all organs, including the hypocotyl and the root. Collectively, our findings show that coffee diterpenes are broad-spectrum defence compounds that protect not only the seed on the mother plant and in the soil, but also the seedling after germination.
Topics: Humans; Coffea; Coffee; Seedlings; Antifungal Agents; Endosperm; Germination; Diterpenes; Seeds; Fatty Acids
PubMed: 36535102
DOI: 10.1016/j.plaphy.2022.12.013 -
Molecules (Basel, Switzerland) Apr 2024Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are... (Review)
Review
Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are particularly notable. These terpenes are characterized by their unique 5/7/6/5 tetracyclic system and are exclusive to the Ericaceae family of plants. Renowned for their complex structures and broad spectrum of bioactivities, grayanane diterpenes have become a primary focus in extensive phytochemical and pharmacological research. Recent studies, spanning from 2018 to January 2024, have reported a series of new grayanane diterpenes with unprecedented carbon skeletons. These compounds exhibit various biological properties, including analgesic, antifeedant, anti-inflammatory, and inhibition of protein tyrosine phosphatase 1B (PTP1B). This paper delves into the discovery of 193 newly identified grayanoids, representing 15 distinct carbon skeletons within the Ericaceae family. The study of grayanane diterpenes is not only a deep dive into the complexities of natural product chemistry but also an investigation into potential therapeutic applications. Their unique structures and diverse biological actions make them promising candidates for drug discovery and medicinal applications. The review encompasses their occurrence, distribution, structural features, and biological activities, providing invaluable insights for future pharmacological explorations and research.
Topics: Diterpenes; Terpenes; Biological Products; Carbon; Ericaceae
PubMed: 38611928
DOI: 10.3390/molecules29071649 -
Natural Product Reports Jun 2020Covering: 2009 to 2018. Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, are a diverse class of compounds having complex... (Review)
Review
Covering: 2009 to 2018. Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, are a diverse class of compounds having complex structural features with many stereocenters. The important pharmacological activities and structural complexity of the diterpenoid alkaloids have long interested scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. Since 2009, 373 diterpenoid alkaloids, assigned to 46 skeletons, have been isolated and identified from plants mostly in the Ranunculaceae family. The names, classes, molecular weight, molecular formula, NMR data, and plant sources of these diterpene alkaloids are collated here. This review will be a detailed update of the naturally occurring diterpene alkaloids reported from the plant kingdom from 2009-2018, providing an in-depth discussion of their diversity, biological activities, pharmacokinetics, toxicity, application, evolution, and biosynthesis.
Topics: Alkaloids; Analgesics; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Diterpenes; Humans; Molecular Structure
PubMed: 32129397
DOI: 10.1039/d0np00002g -
Bioprocess and Biosystems Engineering Jun 2020Labdane diterpenes and their derivatives have shown remarkable biological activities and are useful as chiral building blocks for the synthesis of a variety of bioactive...
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.
Topics: Biocatalysis; Diterpenes; Fungi; Hydroxylation
PubMed: 32020446
DOI: 10.1007/s00449-020-02303-x -
Natural Product Reports Nov 2022Covering: 2013 to 2021As the characteristic metabolites of plants, diterpenoids have always been a hot topic in related science communities due to their intriguing... (Review)
Review
Covering: 2013 to 2021As the characteristic metabolites of plants, diterpenoids have always been a hot topic in related science communities due to their intriguing structures and broad bioactivities. In this review, we intent to provide an in-depth and extensive coverage of diterpenoids reported from 2013 to the end of 2021, including 997 new diterpenoids and 78 known ones with latest progress. Multiple aspects will be summarized, including their occurrences, chemical structures, bioactivities, and syntheses, in which the structure-activity relationship and biosynthesis of this class will be discussed for the first time.
Topics: Euphorbia; Diterpenes; Structure-Activity Relationship; Molecular Structure
PubMed: 36111621
DOI: 10.1039/d2np00047d -
Molecules (Basel, Switzerland) Sep 2022is a well-known Asian medicinal plant with a major phytoconstituent of diterpene lactones, such as andrographolide, 14-deoxyandrographolide, and neoandrographolide. A... (Review)
Review
is a well-known Asian medicinal plant with a major phytoconstituent of diterpene lactones, such as andrographolide, 14-deoxyandrographolide, and neoandrographolide. A World Health Organization (WHO) monograph on selected medicinal plants showed that extracts and its major diterpene lactones have promising anti-inflammatory, antidiabetic, antimalarial, anticancer, antifungal, antibacterial, antioxidant, and hypoglycemic activities. However, these active phytochemicals have poor water solubility and bioavailability when delivered in a conventional dosage form. These biological barriers can be mitigated if the extract or isolated compound are delivered as nanoparticles. This review discusses existing studies and marketed products of in solid, liquid, semi-solid, and gaseous dosage forms, either as an extract or isolated pure compounds, as well as their deficits in reaching maximum bioavailability. The pharmaceutics and pharmacological activity of as a nano-delivery system are also discussed.
Topics: Andrographis; Andrographis paniculata; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antimalarials; Antioxidants; Diterpenes; Hypoglycemic Agents; Lactones; Plant Extracts; Plants, Medicinal; Water
PubMed: 36234698
DOI: 10.3390/molecules27196164 -
Mini Reviews in Medicinal Chemistry 2022Marine organisms are recognized as a rich source of bioactive secondary metabolites. The remarkable abundance and diversity of bioactive small molecules isolated from...
Marine organisms are recognized as a rich source of bioactive secondary metabolites. The remarkable abundance and diversity of bioactive small molecules isolated from soft corals displayed their essential role in drug discovery for human diseases. Sterols and terpenes, particularly cembranolides, 14-membered cyclic diterpene, demonstrated numerous biological activities, such as antitumor, antimicrobial, antiviral, antidiabetic, anti-osteoporosis and anti-inflammatory. Accordingly, continuous investigation of marine soft corals leads the way to discover a plentiful number of chemical diverse natural products with various biological potentials for prospective pharmaceutical industrial applications. Such review affords plenary inspection of the total secondary metabolites isolated from the Sinularia, from 2008 until 2020, besides their natural sources as well as bioactivities whenever possible.
Topics: Animals; Anthozoa; Biological Products; Diterpenes; Prospective Studies; Terpenes
PubMed: 34579632
DOI: 10.2174/1389557521666210927152249 -
Natural Product Research Dec 2019A new diterpene, cassipouryl hexadecanoate (), in addition to the cassipourol () and four terpenes () were isolated from the twigs and leaves of (Blume) de Laub. The...
A new diterpene, cassipouryl hexadecanoate (), in addition to the cassipourol () and four terpenes () were isolated from the twigs and leaves of (Blume) de Laub. The structures of the two monocyclic diterpenes (, ), were elucidated on the basic of 1D and 2D NMR spectroscopic data and compared with the literature. These two monocyclic diterpenes (, ) were tested for their anti-proliferative activity on acute myeloid leukemia (OCI-AML) cells. The results showed that had significantly anti-proliferative activity whereas was weakly active.
Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Diterpenes; Drug Screening Assays, Antitumor; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Spectroscopy; Molecular Structure; Plant Leaves; Tracheophyta
PubMed: 29781313
DOI: 10.1080/14786419.2018.1477149 -
Pharmacological Research Sep 2020The presence of a fused 5/6/7 tricyclic core characterizes the group of cyathane diterpene natural products, that include more than 170 compounds, isolated from fungi... (Review)
Review
The presence of a fused 5/6/7 tricyclic core characterizes the group of cyathane diterpene natural products, that include more than 170 compounds, isolated from fungi such as Cyathus africanus and Hericium erinaceus. These compounds have a common biosynthetic precursor (cyatha-3,12-diene) and can be produced bio- or hemi-synthetically, or via total syntheses. Cyathane diterpenes display a range of pharmacological properties, including anti-inflammatory (possibly through binding to the iNOS protein) and neuroprotective effects. Many cyathanes like cyahookerin C, cyathin Q and cyafranines B and G can stimulate neurite outgrowth in cells, whereas conversely a few molecules (such as scabronine M) inhibit NGF-stimulated neurite outgrowth. The main anticancer cyathanes are erinacine A and cyathins Q and R, with a capacity to trigger cancer cell death dependent on the production of reactive oxygen species (ROS). These compounds, active both in vitro and in vivo, activate different signaling pathways in tumor cells to induce apoptosis (and autophagy) and to upregulate the expression of several proteins implicated in the organization and functioning of the actin cytoskeleton. An analysis of the functional analogy between erinacine A and other natural products known to interfere with the actin network in a ROS-dependent manner (notably cucurbitacin B) further supports the idea that erinacine A functions as a perturbator of the cytoskeleton organization. Collectively, we provide an overview of the molecular diversity of cyathane diterpenes and the main mechanisms of action of the lead compounds, with the objective to encourage further research with these fungal products. The anticancer potential of erinacine A deserves further attention but it will be necessary to better characterize the implicated targets and signaling pathways.
Topics: Actin Cytoskeleton; Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Diterpenes; Humans; Neoplasms; Nervous System Diseases; Neurons; Neuroprotective Agents; Signal Transduction
PubMed: 32485283
DOI: 10.1016/j.phrs.2020.104953