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Molecules (Basel, Switzerland) Nov 2022Two novel dissymmetric diterpenoids, biselisabethoxanes A and B ( and ), were isolated from the hexane extracts of the gorgonian coral . Biselisabethoxane A ()...
Isolation, Structural Analysis and Biological Activity Assays of Biselisabethoxanes A and B: Two Dissymmetric -Diterpenes from the Southwestern Caribbean Sea Gorgonian Coral .
Two novel dissymmetric diterpenoids, biselisabethoxanes A and B ( and ), were isolated from the hexane extracts of the gorgonian coral . Biselisabethoxane A () represents the first example of a marine-derived C dimer made of two distinct diterpene fragments, whereas biselisabethoxane B () is a fused heterodimer stemming from coupling of two amphilectane-based fragments. The structures of and were elucidated based on 1D and 2D NMR spectral data analysis. The molecular structure of was subsequently confirmed by X-ray crystallographic analysis. When evaluated for their inhibitory effects in a series of well-established biological activity assays the isolated compounds were shown to moderately inhibit the growth of .
Topics: Animals; Anthozoa; Diterpenes; Mycobacterium tuberculosis; Caribbean Region; Molecular Structure
PubMed: 36431975
DOI: 10.3390/molecules27227879 -
Nature Chemical Biology Feb 2021Momilactones from rice have allelopathic activity, the ability to inhibit growth of competing plants. Transferring momilactone production to other crops is a potential...
Momilactones from rice have allelopathic activity, the ability to inhibit growth of competing plants. Transferring momilactone production to other crops is a potential approach to combat weeds, yet a complete momilactone biosynthetic pathway remains elusive. Here, we address this challenge through rapid gene screening in Nicotiana benthamiana, a heterologous plant host. This required us to solve a central problem: diminishing intermediate and product yields remain a bottleneck for multistep diterpene pathways. We increased intermediate and product titers by rerouting diterpene biosynthesis from the chloroplast to the cytosolic, high-flux mevalonate pathway. This enabled the discovery and reconstitution of a complete route to momilactones (>10-fold yield improvement in production versus rice). Pure momilactone B isolated from N. benthamiana inhibited germination and root growth in Arabidopsis thaliana, validating allelopathic activity. We demonstrated the broad utility of this approach by applying it to forskolin, a Hedgehog inhibitor, and taxadiene, an intermediate in taxol biosynthesis (~10-fold improvement in production versus chloroplast expression).
Topics: Alkenes; Arabidopsis; Chloroplasts; Colforsin; Cytosol; Diterpenes; Lactones; Mevalonic Acid; Oryza; Paclitaxel; Plant Leaves; Plant Roots; Plants; Signal Transduction; Nicotiana
PubMed: 33106662
DOI: 10.1038/s41589-020-00669-3 -
Poultry Science Nov 2009Tiamulin hydrogen fumarate is a semisynthetic derivative of the diterpene antibiotic pleuromutilin used in poultry medicine to treat mainly Mycoplasma- and... (Review)
Review
Tiamulin hydrogen fumarate is a semisynthetic derivative of the diterpene antibiotic pleuromutilin used in poultry medicine to treat mainly Mycoplasma- and Brachyspira-related diseases. Its use over 30 yr has not generally increased the development of resistance to these pathogens but occasionally resistant isolates are encountered. Tiamulin administered at therapeutic levels is relatively quickly absorbed, metabolized in the liver, and eliminated from the body of the bird after a withdrawal period of 72 h, and as a result, meat products can be safely consumed. A zero withdrawal period for eggs has been granted in several European Union states. When administered with different drugs, tiamulin has been shown to have an enhanced activity with the tetracyclines. There is a strong interaction, even death, with the ionophore anticoccidials monensin, narasin, and salinomycin when tiamulin is used at therapeutic levels, but this is dose-related and low doses do not interact. It is thought to be caused by the preferential metabolism of tiamulin in the liver resulting in a build up of the ionophore leading to clinical signs of overdosage. Tiamulin shows a milder interaction, such as temporary growth depression, with maduramicin and semduramicin but is compatible with lasalocid. Although tiamulin shows small benefits in improving performance in healthy animals, its main production benefit is in the face of infection, as a true therapeutic antibiotic.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Diterpenes; Poultry; Poultry Diseases
PubMed: 19834086
DOI: 10.3382/ps.2009-00257 -
Molecules (Basel, Switzerland) May 2013Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been...
Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5) and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8-10, differing in the number of CH₂ units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC₅₀ values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM). The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC₅₀ values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation.
Topics: Cell Proliferation; Diterpenes; Fibroblasts; HL-60 Cells; Humans; Methylation
PubMed: 23698047
DOI: 10.3390/molecules18055936 -
Phytochemistry Oct 2021The pseudoalkaloid diterpene Taxol® (paclitaxel) emerged as a best-selling anti-cancer drug in the mid-1990s. The compound attracted considerable interest because of... (Review)
Review
The pseudoalkaloid diterpene Taxol® (paclitaxel) emerged as a best-selling anti-cancer drug in the mid-1990s. The compound attracted considerable interest because of its unique mechanism to stabilize microtubules, thus reducing dynamicity and ultimately promoting mitotic arrest. Taxol was originally isolated from members of the genus Taxus. Over the last 50 years, close to 600 metabolites with taxane scaffolds were isolated from various Taxus species and their structures reported. The present review article provides an overview of the known chemical diversity of taxanes, with an emphasis on the functionalization of diterpene scaffolds. The implications of the occurrence of chemically diverse taxane metabolites for unraveling Taxol biosynthesis and enabling pathway engineering are discussed as well.
Topics: Antineoplastic Agents; Diterpenes; Paclitaxel; Taxoids; Taxus
PubMed: 34329937
DOI: 10.1016/j.phytochem.2021.112829 -
Chemical & Pharmaceutical Bulletin 2018Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and...
Absolute Structures of Wedelolide Derivatives and Structure-Activity Relationships of Protein Tyrosine Phosphatase 1B Inhibitory ent-Kaurene Diterpenes from Aerial Parts of Wedelia spp. Collected in Indonesia and Japan.
Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.
Topics: Cell Line, Tumor; Diterpenes; Enzyme Inhibitors; Hep G2 Cells; Humans; Indonesia; Japan; Molecular Structure; Plant Components, Aerial; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Structure-Activity Relationship; Wedelia
PubMed: 29863070
DOI: 10.1248/cpb.c18-00117 -
Marine Drugs May 2018Species of the brown algae of the genus are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the... (Review)
Review
Species of the brown algae of the genus are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus.
Topics: Animals; Antiviral Agents; Aquatic Organisms; Cytotoxins; Diterpenes; Humans; Phaeophyceae
PubMed: 29751686
DOI: 10.3390/md16050159 -
Molecules (Basel, Switzerland) Jul 2019To obtain diterpene glycosides from an aqueous extract of the aerial parts of and further investigate their cytotoxicities, in this study, a total of seven compounds...
To obtain diterpene glycosides from an aqueous extract of the aerial parts of and further investigate their cytotoxicities, in this study, a total of seven compounds were isolated, including six -kaurane diterpene glycosides (-) and one diterpene aglycon (7). Among the seven -kaurane diterpenes obtained, four were novel compounds, including ent-7,20-epoxy- kaur-16-en-1α,6β,7β,15β-tetrahydroxyl-11-O-β-d-glucopyranoside (), -7,20-epoxy-kaur-16-en- 6,7,14,15-tetrahydroxyl-1---d-glucopyranoside (), -7,20-epoxy-kaur-16-en-6,7,15- trihydroxyl-1---d-glucopyranoside (), and -7,20-epoxy-kaur-16-en-7,11,14α,15-tetrahydr- oxyl-6---d-glucopyranoside (), and three were isolated from this plant for the first time (-7). Their structures were elucidated by utilizing spectroscopic methods and electronic circular dichroism analyses. Furthermore, the cytotoxicities of all seven compounds were investigated in four human cancer cell lines, including A2780, BGC-823, HCT-116, and HepG2. The IC values of these diterpenes ranged from 0.18 to 2.44 mM in the tested cell lines. In addition, the structure-cytotoxicity relationship of diterpene glycosides was also evaluated to study the effect of glycosylation on the cytotoxicity of diterpene compounds.
Topics: Antineoplastic Agents, Phytogenic; Diterpenes, Kaurane; Glycosides; Isodon; Models, Molecular; Molecular Structure; Spectrum Analysis; Structure-Activity Relationship
PubMed: 31357638
DOI: 10.3390/molecules24152736 -
International Journal of Molecular... Jan 2023A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared...
A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an ,-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic -substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.
Topics: Female; Humans; Cell Line, Tumor; Ovarian Neoplasms; Diterpenes; HeLa Cells; Cell Proliferation; Antineoplastic Agents; Structure-Activity Relationship; Molecular Structure; Drug Screening Assays, Antitumor
PubMed: 36674639
DOI: 10.3390/ijms24021121 -
Molecules (Basel, Switzerland) Nov 2019Enzymatic inhibitions of crude extracts and their constituents from Zingiberaceae against both rat intestinal α-glucosidase and porcine pancreatic lipase were...
Enzymatic inhibitions of crude extracts and their constituents from Zingiberaceae against both rat intestinal α-glucosidase and porcine pancreatic lipase were investigated. Structure-activity relationships using their derivatives were also investigated. The rhizomes extract of mango ginger, showed remarkable inhibitory activity in the screening test. Two natural labdane diterpenes and and a drimane sesquiterpene were major constituents isolated from this hexane extract. Among them, ()-labda-8(17),12-diene-15,16-dial () was the most prominent compound and showed inhibitory activity against both α-glucosidase and lipase. Derivatives - from compound were prepared and evaluated using inhibitory assays with these enzymes. The reduced derivative maintained α-glucosidase inhibitory activity, but had decreased pancreatic lipase inhibitory activity compared with parent compound . Other tested derivatives of compound , including acetates - and oxidative derivatives , had very weak α-glucosidase inhibitory activity. Most of these compounds showed moderate pancreatic lipase inhibitory activity. However, only sesquiterpene albicanal () showed drastically decreased pancreatic lipase activity compared with . These findings suggested that molecular size was essential for enzymatic inhibitory activities of these compounds. These results demonstrated that mango ginger may be useful for the prevention of obesity and being overweight.
Topics: Animals; Diterpenes; Enzyme Activation; Enzyme Inhibitors; Zingiber officinale; Glycoside Hydrolase Inhibitors; Molecular Structure; Pancrelipase; Plant Extracts; Rats; alpha-Glucosidases
PubMed: 31717689
DOI: 10.3390/molecules24224071