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International Journal of Molecular... Jan 2024New substances with antimicrobial properties are needed to successfully treat emerging human, animal, or plant pathogens. Seven clerodane diterpenes, previously isolated...
New substances with antimicrobial properties are needed to successfully treat emerging human, animal, or plant pathogens. Seven clerodane diterpenes, previously isolated from giant goldenrod () root, were tested against Gram-positive , and by measuring minimal bactericidal concentration (MBC), minimal inhibitory concentration (MIC) and half-maximal inhibitory concentration (IC). Two of them, Sg3a (a dialdehyde) and Sg6 (solidagoic acid B), were proved to be the most effective and were selected for further study. was incubated with the two diterpenes for shorter (1 h) or longer (5 h) periods and then subjected to genome-wide transcriptional analyses. Only a limited number of common genes (28 genes) were differentially regulated after each treatment, and these were mainly related to the restoration of cell membrane integrity and to membrane-related transports. Changes in gene activity indicated that, among other things, K and Na homeostasis, pH and membrane electron transport processes may have been affected. Activated export systems can be involved in the removal of harmful molecules from the bacterial cells. Inhibition of bacterial chemotaxis and flagellar assembly, as well as activation of genes for the biosynthesis of secondary metabolites, were observed as a general response. Depending on the diterpenes and the duration of the treatments, down-regulation of the protein synthesis-related, oxidative phosphorylation, signal transduction and transcription factor genes was found. In other cases, up-regulation of the genes of oxidation-reduction processes, sporulation and cell wall modification could be detected. Comparison of the effect of diterpenes with the changes induced by different environmental and nutritional conditions revealed several overlapping processes with stress responses. For example, the Sg6 treatment seems to have caused a starvation-like condition. In summary, there were both common and diterpene-specific changes in the transcriptome, and these changes were also dependent on the length of treatments. The results also indicated that Sg6 exerted its effect more slowly than Sg3a, but ultimately its effect was greater.
Topics: Animals; Humans; Diterpenes, Clerodane; Solidago; Diterpenes; Anti-Infective Agents; Bacillus subtilis; Cell Membrane
PubMed: 38338810
DOI: 10.3390/ijms25031531 -
Natural Product Reports Nov 2010In his original exposition of the biogenetic isoprenoid rule, L. Ruzicka noted the structural identity between the fused A/B rings of triterpenoids/sterols and certain... (Review)
Review
In his original exposition of the biogenetic isoprenoid rule, L. Ruzicka noted the structural identity between the fused A/B rings of triterpenoids/sterols and certain multicyclic diterpenoids as part of the impetus leading to that profound insight. His prescient hypothesis that this chemical structure relationship reflects similarities in the initial cyclization of these diterpenoids with that occurring in triterpenoid biosynthesis has since been verified. However, this chemical structure relationship does not continue to hold true for the additional rings found in many of these di- and tri- terpenoid natural products. This is now appreciated to arise from differences in their subsequent biogenesis, specifically further cyclization and/or rearrangement of these diterpenoids after formation of an initial bicyclic intermediate in a separately catalyzed reaction. The trivial name for the hydrocarbon skeleton of the most commonly found version of the corresponding unique intermediate forms the basis for a unifying “” designation. This defines a large super-family of diterpenoids that contains nearly 7,000 already known natural products. Many of these are found in plants, where the requisite biosynthetic machinery for gibberellin phytohormones, particularly the relevant diterpene cyclases, provides a biosynthetic reservoir that appears to have been repeatedly drawn upon to evolve new labdane-related diterpenoids. The potent biological activity of the “ancestral” gibberellins, which has led to the independent evolution of distinct gibberellin biosynthetic pathways in plants, fungi, and bacteria, is further discussed as an archetypical example of the selective pressure driving the observed diversification of the large super-family of labdane-related diterpenoid natural products.
Topics: Biological Products; Cyclization; Diterpenes; Molecular Structure; Stereoisomerism
PubMed: 20890488
DOI: 10.1039/c0np00019a -
Molecules (Basel, Switzerland) Dec 2018Three new -kauran-type diterpenes (⁻), named arenterpenoids A⁻C, and five known ones (⁻) were isolated and identified from (Wurmb.) Merr. Fruits. The structures...
Three new -kauran-type diterpenes (⁻), named arenterpenoids A⁻C, and five known ones (⁻) were isolated and identified from (Wurmb.) Merr. Fruits. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. To the best of our knowledge, this is the first scientific report of diterpenes from genus.
Topics: Arecaceae; Carbon-13 Magnetic Resonance Spectroscopy; Diterpenes; Fruit; Proton Magnetic Resonance Spectroscopy
PubMed: 30591647
DOI: 10.3390/molecules24010087 -
Journal of the American Chemical Society Aug 2016An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in...
An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (-)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product.
Topics: Biomimetics; Chemistry Techniques, Synthetic; Diterpenes; Models, Molecular; Molecular Conformation; Stereoisomerism
PubMed: 27457680
DOI: 10.1021/jacs.6b06623 -
Fitoterapia Jun 2011A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures...
A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic methods (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding.
Topics: Diterpenes; Drugs, Chinese Herbal; Flavonoids; Fruit; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Phenols; Spectrometry, Mass, Electrospray Ionization; Terpenes; Vitex
PubMed: 21163339
DOI: 10.1016/j.fitote.2010.12.003 -
Nature Sep 2019(+)-Perseanol is an isoryanodane diterpene that is isolated from the tropical shrub Persea indica and has potent antifeedant and insecticidal properties. It is...
(+)-Perseanol is an isoryanodane diterpene that is isolated from the tropical shrub Persea indica and has potent antifeedant and insecticidal properties. It is structurally related to (+)-ryanodine, which is a high-affinity ligand for and modulator of ryanodine receptors-ligand-gated ion channels that are critical for intracellular Ca signalling in most multicellular organisms. Ryanodine itself modulates ryanodine-receptor-dependent Ca release in many organisms, including mammals; however, preliminary data indicate that ryanodane and isoryanodane congeners that lack the pyrrole-2-carboxylate ester-such as perseanol-may have selective activity in insects. Here we report a chemical synthesis of (+)-perseanol, which proceeds in 16 steps from commercially available (R)-pulegone. The synthesis involves a two-step annulation process that rapidly assembles the tetracyclic core from readily accessible cyclopentyl building blocks. This work demonstrates how convergent fragment coupling, when combined with strategic oxidation tactics, can enable the concise synthesis of complex and highly oxidized diterpene natural products.
Topics: Biological Products; Chemistry Techniques, Synthetic; Cyclohexane Monoterpenes; Diterpenes; Persea
PubMed: 31554978
DOI: 10.1038/s41586-019-1580-x -
Molecules (Basel, Switzerland) Feb 2019This work reviews the new isolated cembranoid derivatives from species of the genera , , and as well as their biological properties, during 2016⁻2018. The compilation... (Review)
Review
This work reviews the new isolated cembranoid derivatives from species of the genera , , and as well as their biological properties, during 2016⁻2018. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus than in those belonging to the genera or . Beyond the chemical composition, the biological properties were also reviewed, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. In spite of the biological activities detected in almost all samples, there is a remarkable diversity in the results which may be attributed to the chemical variability that needs to be deepened in order to develop new molecules with potential application in medicine.
Topics: Animals; Anthozoa; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antineoplastic Agents; Bacteria; Cell Line, Tumor; Cell Survival; Diterpenes; Fungi; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Structure-Activity Relationship
PubMed: 30795596
DOI: 10.3390/molecules24040781 -
Organic Letters Jul 2023The biomimetic formal synthesis of the antibiotic platensimycin for the treatment of infection by multidrug-resistant bacteria was accomplished starting from either...
The biomimetic formal synthesis of the antibiotic platensimycin for the treatment of infection by multidrug-resistant bacteria was accomplished starting from either -kaurenoic acid or grandiflorenic acid, each of which is a natural compound available in multigram scale from its natural source. Apart from the natural origin of the selected precursors, the keys of the described approach are the long-distance functionalization of -kaurenoic acid at C11 and the efficient protocol for the A-ring degradation of the diterpene framework.
Topics: Diterpenes; Adamantane; Aminobenzoates
PubMed: 37338151
DOI: 10.1021/acs.orglett.3c01470 -
Plant Physiology May 2022Spiro-9,13-epoxy-labdane diterpenoids are commonly found in Leonurus species, particularly in Leonurus japonicus Houtt., which is a medicinal herb of long-standing use...
Spiro-9,13-epoxy-labdane diterpenoids are commonly found in Leonurus species, particularly in Leonurus japonicus Houtt., which is a medicinal herb of long-standing use in Asia and in which such spiro-heterocycles are present in at least 38 diterpenoids. Here, through generation of a transcriptome and functional characterization of six diterpene synthases (diTPSs) from L. japonicus, including three class II diTPSs (LjTPS1, LjTPS3, and LjTPS4) and three class I diTPSs (LjTPS5, LjTPS6, and LjTPS7), formation of the spiro-9,13-epoxy-labdane backbone was elucidated, along with identification of the relevant diTPSs for production of other labdane-related diterpenes. Similar to what has been found with diTPSs from other plant species, while LjTPS3 specifically produces the carbon-9 (C9) hydroxylated bicycle peregrinol diphosphate (PPP), the subsequently acting LjTPS6 yields a mixture of four products, largely labda-13(16),14-dien-9-ol, but with substantial amounts of viteagnusin D and the C13-S/R epimers of 9,13-epoxy-labda-14-ene. Notably, structure-function analysis identified a critical residue in LjTPS6 (I420) in which single site mutations enable specific production of the 13S epimer. Indeed, extensive mutagenesis demonstrated that LjTPS6:I420G reacts with PPP to both specifically and efficiently produce 9,13S-epoxy-labda-14-ene, providing a specialized synthase for further investigation of derived diterpenoid biosynthesis. The results reported here provide a strong foundation for future studies of the intriguing spiro-9,13-epoxy-labdane diterpenoid metabolism found in L. japonicus.
Topics: Alkyl and Aryl Transferases; Diterpenes; Leonurus; Plants, Medicinal; Transcriptome
PubMed: 35157086
DOI: 10.1093/plphys/kiac056 -
Marine Drugs Jan 2023The present investigation of the South China Sea soft coral resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A-E (, , -) along with...
The present investigation of the South China Sea soft coral resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A-E (, , -) along with four known ones, , , , and . Based on extensive spectroscopic data analysis, sartrocheliol A () was identified as an uncommon capnosane diterpene, while sartrocheliols B-E (, -) were established as cembrane diterpenes. They displayed diverse structural features not only at the distinctly different carbon frameworks but also at the various types of heterocycles, including the epoxide, γ-lactone, furan, and pyran rings. Moreover, their absolute configurations were determined by a combination of quantum mechanical-nuclear magnetic resonance (QM-NMR) approach, modified Mosher's method, and X-ray diffraction analysis. In the anti-tumor bioassay, compound exhibited moderate cytotoxic activities against A549, H1975, MDA-MB-231, and H1299 cells with the IC values ranging from 26.3 to 47.9 μM.
Topics: Animals; Molecular Structure; Anthozoa; Magnetic Resonance Spectroscopy; Diterpenes; China
PubMed: 36827110
DOI: 10.3390/md21020069