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Marine Drugs Nov 2023Two new cyclopiane diterpenes and a new cladosporin precursor, together with four known related compounds, were isolated from the marine sediment-derived fungus KMM...
Two new cyclopiane diterpenes and a new cladosporin precursor, together with four known related compounds, were isolated from the marine sediment-derived fungus KMM 4670, which was re-identified based on phylogenetic inference from ITS, , , and gene regions. The absolute stereostructures of the isolated cyclopianes were determined using modified Mosher's method and quantum chemical calculations of the ECD spectra. The isolation from the natural source of two biosynthetic precursors of cladosporin from a natural source has been reported for the first time. The antimicrobial activities of the isolated compounds against , , and as well as the inhibition of staphylococcal sortase A activity were investigated. Moreover, the cytotoxicity of the compounds to mammalian cardiomyocytes H9c2 was studied. As a result, new cyclopiane diterpene 13--conidiogenone F was found to be a sortase A inhibitor and a promising anti-staphylococcal agent.
Topics: Animals; Molecular Structure; Polyketides; Phylogeny; Penicillium; Staphylococcus; Diterpenes; Geologic Sediments; Mammals
PubMed: 37999408
DOI: 10.3390/md21110584 -
Chembiochem : a European Journal of... Dec 2021Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker... (Review)
Review
Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker disease of Italian cypress (Cupressus sempervirens L.). It was also produced, together with several analogues, by different pathogenic Diplodia species and other fungi and showed a broad array of biological activities suggesting its promising application in agriculture and medicine. The anticancer activity of SphA is very potent and cell specific. Recent studies have revealed its unique mode of action. This minireview reports the structures of SphA and its family of natural analogues, their biosynthetic origins, their fungal sources, and biological activities. The preparation of various SphA derivatives is also described as well as the results of structure-activity relationship (SAR) studies and on their potential practical applications.
Topics: Antifungal Agents; Antineoplastic Agents; Ascomycota; Diterpenes; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship
PubMed: 34241944
DOI: 10.1002/cbic.202100283 -
Current Opinion in Chemical Biology Apr 2012Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging.... (Review)
Review
Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering.
Topics: Bacteria; Biological Products; Biosynthetic Pathways; Diterpenes; Phylogeny; Protein Engineering
PubMed: 22445175
DOI: 10.1016/j.cbpa.2012.03.002 -
Phytochemistry Mar 2007Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been... (Review)
Review
Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Diterpenes; Drugs, Chinese Herbal; Epoxy Compounds; Immunosuppressive Agents; Molecular Structure; Phenanthrenes; Plant Extracts; Tripterygium
PubMed: 17250858
DOI: 10.1016/j.phytochem.2006.11.029 -
Chemical & Pharmaceutical Bulletin 2021An investigation into the methanol extracts obtained from the stems of Dodonaea viscosa led to the isolation of one nor-clerodane diterpene (1) and two labdane...
An investigation into the methanol extracts obtained from the stems of Dodonaea viscosa led to the isolation of one nor-clerodane diterpene (1) and two labdane diterpenes (2, 3), as well as 17 known compounds (4-20). The structures of these compounds were elucidated based on chemical and spectral evidence. The stereochemical structure of the nor-clerodane diterpene was confirmed via its circular dichroism spectrum and calculated electronic circular dichroism spectrum. Isolated compounds were evaluated for their inhibitory effects on collagenase and tyrosinase. Since 5,7,4'-trihydroxy-3'-(4-hydroxy-3-methylbutyl)-5'-(3-methylbut-2-enyl)-3,6-dimethoxyflavone (9) showed collagenase inhibitory activity and scopoletin (12) had significant tyrosinase inhibitory activity, they were considered to be good candidates for cosmetic agents.
Topics: Agaricales; Diterpenes; Gelatinases; Molecular Structure; Monophenol Monooxygenase; Plant Extracts; Sapindaceae; Stereoisomerism
PubMed: 33390520
DOI: 10.1248/cpb.c20-00327 -
Phytochemistry May 2019In plant terpene biosynthesis, oxidation of the hydrocarbon backbone produced by terpene synthases is typically carried out by cytochrome P450 oxygenases (CYPs). The... (Review)
Review
In plant terpene biosynthesis, oxidation of the hydrocarbon backbone produced by terpene synthases is typically carried out by cytochrome P450 oxygenases (CYPs). The modifications introduced by CYPs include hydroxylations, sequential oxidations at one position and ring rearrangements and closures. These reactions significantly expand the structural diversity of terpenoids, but also provide anchoring points for further decorations by various transferases. In recent years, there has been a significant increase in reports of CYPs involved in plant terpene pathways. Plant diterpenes represent an important class of metabolites that includes hormones and a number of industrially relevant compounds such as pharmaceutical, aroma or food ingredients. In this review, we provide a comprehensive survey on CYPs reported to be involved in plant diterpene biosynthesis to date. A phylogenetic analysis showed that only few CYP clans are represented in diterpene biosynthesis, namely CYP71, CYP85 and CYP72. Remarkably few CYP families and subfamilies within those clans are involved, indicating specific expansion of these clades in plant diterpene biosynthesis. Nonetheless, the evolutionary trajectory of CYPs of specialized diterpene biosynthesis is diverse. Some are recently derived from gibberellin biosynthesis, while others have a more ancient history with recent expansions in specific plant families. Among diterpenoids, labdane-related diterpenoids represent a dominant class. The availability of CYPs from diverse plant species able to catalyze oxidations in specific regions of the labdane-related backbones provides opportunities for combinatorial biosynthesis to produce novel diterpene compounds that can be screened for biological activities of interest.
Topics: Cytochrome P-450 Enzyme System; Diterpenes; Phylogeny; Plants
PubMed: 30733060
DOI: 10.1016/j.phytochem.2018.12.003 -
Biomedicine & Pharmacotherapy =... Feb 2022Andrographis paniculata (A. paniculata) is a traditional herbal medicine that has been widely used in Asian countries for hundreds of years. Andrographolide (AG) is a... (Review)
Review
Andrographis paniculata (A. paniculata) is a traditional herbal medicine that has been widely used in Asian countries for hundreds of years. Andrographolide (AG) is a diterpene lactone extracted from A. paniculata. Owing to the in-depth study of pharmacological mechanisms, the therapeutic potential of AG, including its anti-inflammatory, anti-tumor, and immunoregulatory attributes, has attracted the attention of many researchers. Studies testing the therapeutic effects of AG have demonstrated desirable results in the treatment of a variety of clinical diseases. With high safety and various biological functions, AG might be a promising candidate for the treatment of musculoskeletal disorders. Here, we review all available literatures to summarize the pharmacological effects of AG and facilitate further researches on musculoskeletal diseases.
Topics: Andrographis paniculata; Animals; Arthritis; Cell Line; Diterpenes; Drug Interactions; Humans; Intervertebral Disc Degeneration; Medicine, Traditional; Musculoskeletal Diseases; Osteoporosis
PubMed: 34954644
DOI: 10.1016/j.biopha.2021.112583 -
Current Opinion in Plant Biology Apr 2022Tanshinones are the bioactive diterpenoid constituents of the traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), and are examples of the phenolic... (Review)
Review
Tanshinones are the bioactive diterpenoid constituents of the traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), and are examples of the phenolic abietanes widely found within the Lamiaceae plant family. Due to the significant interest in these labdane-related diterpenoid natural products, their biosynthesis has been intensively investigated. In addition to providing the basis for metabolic engineering efforts, this work further yielded pioneering insights into labdane-related diterpenoid biosynthesis in the Lamiaceae more broadly. This includes stereochemical foreshadowing of aromatization, with novel protein domain loss in the relevant diterpene synthase, as well as broader phylogenetic conservation of the relevant enzymes. Beyond such summary of more widespread metabolism, formation of the furan ring that characterizes the tanshinones also has been recently elucidated. Nevertheless, the biocatalysts for the pair of demethylations remain unknown, and the intriguing potential connection of these reactions to the further aromatization observed in the tanshinones are speculated upon here.
Topics: Abietanes; Diterpenes; Lamiaceae; Phylogeny; Salvia miltiorrhiza
PubMed: 35196638
DOI: 10.1016/j.pbi.2022.102189 -
Yakugaku Zasshi : Journal of the... 2011In interviews on the traditional herbal medicines of Tupi-Guarany Indians at the herbal market of Asuncion and questionnaire from their users, it was clarified that... (Review)
Review
In interviews on the traditional herbal medicines of Tupi-Guarany Indians at the herbal market of Asuncion and questionnaire from their users, it was clarified that various useful medicinal plants are available in Paraguay and most of them are generally used without drying. In the search for bioactive substances from those plants, a β-glucuronidase-inhibitory diterpene called scoparic acid A (SA) was isolated from Scoparia dulcis L. together with scoparic acid B, scoparic acid C, and the aphidicolin-like tetracyclic diterpenes scopadulcic acid A (SDA) and scopadulcic acid B (SDB). HPLC analysis of diterpenes in the individual plants of Paraguayan and Asian S. dulcis revealed the presence of three chemotypes based on major component, i.e., SA type, SDB type, and SDX type containing mainly scopadiol and scopadulciol (SDC). SA and SDB were elucidated to be mainly biosynthesized in the leaves via 2-C-methyl-D-erythritol- 4-phosphate pathway, and a leaf organ culture system containing methyl jasmonate 10 µM was found to enhance the production of diterpenes by activation of Ca-signal transduction systems such as calmodulin and protein kinase C. On the other hand, SDB and SDC were found to show multifaceted pharmacological effects such as inhibitory effects on gastric acid excretion, bone resorption, replication of herpes simplex virus type 1 (HSV-1), etc. In addition, SDC was suggested to be applicable to cancer gene therapy using ganciclovir or acyclovir and the HSV-1 thymidine kinase gene called the suicide gene.
Topics: Abietanes; Animals; Bone Resorption; Chromatography, High Pressure Liquid; Diterpenes; Gastric Acid; Genes, Transgenic, Suicide; Genetic Therapy; Herpesvirus 1, Human; Humans; Medicine, Traditional; Neoplasms; Paraguay; Phytotherapy; Rats; Scoparia; Surveys and Questionnaires; Thymidine Kinase; Virus Replication
PubMed: 21881299
DOI: 10.1248/yakushi.131.1259 -
Nature Apr 2016Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to...
Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to its intriguing chemical structure and the medicinal potential of phorbol esters. Access to useful quantities of phorbol and related analogues has relied on isolation from natural sources and semisynthesis. Despite efforts spanning 40 years, chemical synthesis has been unable to compete with these strategies, owing to its complexity and unusual placement of oxygen atoms. Purely synthetic enantiopure phorbol has remained elusive, and biological synthesis has not led to even the simplest members of this terpene family. Recently, the chemical syntheses of eudesmanes, germacrenes, taxanes and ingenanes have all benefited from a strategy inspired by the logic of two-phase terpene biosynthesis in which powerful C-C bond constructions and C-H bond oxidations go hand in hand. Here we implement a two-phase terpene synthesis strategy to achieve enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene. The purpose of this synthesis route is not to displace isolation or semisynthesis as a means of generating the natural product per se, but rather to enable access to analogues containing unique placements of oxygen atoms that are otherwise inaccessible.
Topics: Bicyclic Monoterpenes; Biological Products; Chemistry Techniques, Synthetic; Diterpenes; Molecular Structure; Monoterpenes; Oxygen; Phorbol Esters; Phorbols; Stereoisomerism
PubMed: 27007853
DOI: 10.1038/nature17153