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Molecules (Basel, Switzerland) Apr 2015Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the...
Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic, kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they show significant changes in viability of tumoral line cells. The 3-hydroxy-copalic was able to inhibit the enzyme tyrosinase (64% ± 1.5%) at 250 µM. The kolavic-15-metyl ester at 200 µM showed high inhibitory effect on lipoxygenase (89.5% ± 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids showed significant hemolytic activities with 61.7% and 38.4% at 100 µM, respectively. In addition, it was observed that only the copalic acid (98.5% ± 1.3%) and hardwickiic acid (92.7% ± 4.9%) at 100 mM inhibited nitric oxide production in macrophages activated by lipopolysaccharide. In this assay, the diterpenes did not inhibit tumor necrosis factor-α production. The acids inhibited the production of IL-6, 3-acetoxy-copalic (23.8% ± 8.2%), kaurenoic (11.2% ± 5.7%), kolavic-15-methyl ester (17.3% ± 4.2%), and copalic (4.2% ± 1.8%), respectively, at 25 µM. The kaurenoic, 3-acetoxy-copalic and copalic acids increased IL-10 production. This study may provide a basis for future studies on the therapeutic role of diterpenic acids in treating acute injuries such as inflammation or skin disorders.
Topics: Animals; Cell Line; Cell Proliferation; Diterpenes; Fabaceae; Hemolysis; Humans; Inflammation; Lipopolysaccharides; Macrophages; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Nitric Oxide; Plant Extracts; Rats
PubMed: 25859778
DOI: 10.3390/molecules20046194 -
International Journal of Molecular... Nov 2022The incidence of diabetes mellitus (DM), one of the most common chronic metabolic disorders, has increased dramatically over the past decade and has resulted in higher...
The incidence of diabetes mellitus (DM), one of the most common chronic metabolic disorders, has increased dramatically over the past decade and has resulted in higher rates of morbidity and mortality worldwide. The enzyme, α-Glucosidase (α-GLy), is considered a therapeutic target for the treatment of type 2 DM. Herein, we synthesized arylidene, heterocyclic, cyanoetoxy- and propargylated derivatives of quinopimaric acid (levopimaric acid diene adduct with -benzoquinone) - and, first, evaluated their ability to inhibit α-GLy. Among the tested compounds, quinopimaric acid , 2,3-dihydroquinopimaric acid and its amide and heterocyclic derivatives , , , , , with IC values of 35.57-65.98 μM, emerged as being good inhibitors of α-GLy. Arylidene 1β-hydroxy and 1β,13α-epoxy methyl dihydroquinopimarate derivatives , , -, thiadiazole , 1a,4a-dehydroquinopimaric acid and its indole, nitrile and propargyl hybrids -, , , , and showed excellent inhibitory activities. The most active compounds , , , and displayed IC values of 0.15 to 0.68 μM, being 1206 to 266 more active than acarbose (IC of 181.02 μM). Kinetic analysis revealed the most active diterpene indole with an alkyne substituent as a competitive inhibitor with of 50.45 μM. Molecular modeling supported this finding and suggested that the indole core plays a key role in the binding. Compound also has favorable pharmacokinetic and safety properties, according to the computational ADMET profiling. The results suggested that quinopimaric acid derivatives should be considered as potential candidates for novel alternative therapies in the treatment of type 2 diabetes.
Topics: Humans; alpha-Glucosidases; Diabetes Mellitus, Type 2; Kinetics; Diterpenes; Indoles; Glycoside Hydrolase Inhibitors; Molecular Docking Simulation; Structure-Activity Relationship; Molecular Structure
PubMed: 36362322
DOI: 10.3390/ijms232113535 -
Journal of Natural Medicines Jun 2023To this day, since about 50% of all medicines are derived from natural sources, natural product chemistry, especially the search for biologically active natural... (Review)
Review
To this day, since about 50% of all medicines are derived from natural sources, natural product chemistry, especially the search for biologically active natural components, remains extremely important (Newman and Cragg in J Nat Prod 83:770-803, 2020). In this review, we deal with our continuing research work for promising constituents from plants collected in the Ryukyu Archipelago. The isolation of islands in the archipelago by the sea or by straits gives rise to endemic plant species that are unique to the islands. The structural diversity of the constituents produced by this unique flora is of great scientific interest in various aspects, including chemical structures, biosynthesis, and biological activities. The components from this structural diversity have great potential as new pharmaceutical seeds. In our continuing studies, we have successfully investigated new but extremely unusual diterpenoids: crotofolanes and their rearranged varieties (nor-crotofolane, trinor-crotofolane, neocrotofolane) and a glycoside with a new skeletal diterpenoid (isocrotofolane glucoside) from Croton cascarilloides. This review summarizes our reports on the investigation of crotofolanes as well as those on crotofolanes by other research groups.
Topics: Croton; Glycosides; Glucosides; Diterpenes; Plants
PubMed: 37083998
DOI: 10.1007/s11418-023-01698-7 -
Marine Drugs Mar 2024Five new biflorane-type diterpenoids, biofloranates E-I (-), and two new bicyclic diterpene glycosides, lemnaboursides H-I (-), along with the known lemnabourside, were...
Five new biflorane-type diterpenoids, biofloranates E-I (-), and two new bicyclic diterpene glycosides, lemnaboursides H-I (-), along with the known lemnabourside, were isolated from the South China Sea soft coral . Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against and , with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 μM.
Topics: Anthozoa; Diterpenes; Anti-Bacterial Agents; Animals; Glycosides; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Bacillus subtilis; HeLa Cells; Cell Line, Tumor; Hep G2 Cells; Molecular Structure; A549 Cells; China
PubMed: 38667774
DOI: 10.3390/md22040157 -
Chemical & Pharmaceutical Bulletin Jun 2018We isolated two new lathyrane-type diterpenes L (1) and L (2) along with seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds were...
We isolated two new lathyrane-type diterpenes L (1) and L (2) along with seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with H-NMR, C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by comprehensive interpretation of their nuclear Overhauser effect (NOE) relationship and showed they were first natural lathyrane-type diterpenes possessing α-configuration substitutes at C-3. Cytotoxicity assay of isolated compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231, 786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L (2) showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC value of 9.43 and 13.22 µM, respectively, which preliminarily suggested that the configuration of lathyrane-type diterpene at C-3 has a significant effect on its bioactivity.
Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Diterpenes; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Euphorbia; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Conformation; Plant Extracts; Seeds; Structure-Activity Relationship
PubMed: 29593174
DOI: 10.1248/cpb.c17-00946 -
Pharmacological Reports : PR 2011The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the... (Comparative Study)
Comparative Study Review
The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.
Topics: Animals; Depression; Diterpenes, Clerodane; Humans; Pain; Psychotropic Drugs; Salvia
PubMed: 22358078
DOI: 10.1016/s1734-1140(11)70694-6 -
Natural Product Reports Dec 2015Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as... (Review)
Review
Covering January to December 2014. Previous review, Nat. Prod. Rep., 2015, 32, 76-87 This review covers the isolation and chemistry of diterpenoids from terrestrial as opposed to marine sources and includes, labdanes, clerodanes, abietanes, pimaranes, kauranes, cembranes and their cyclization products. There are 200 references.
Topics: Diterpenes; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular
PubMed: 26514379
DOI: 10.1039/c5np00087d -
Marine Drugs Jun 2021A chemical study on the extracts of soft coral resulted in the isolation and identification of six new bicyclic diterpene glycosides including three new lemnaboursides...
A chemical study on the extracts of soft coral resulted in the isolation and identification of six new bicyclic diterpene glycosides including three new lemnaboursides E-G (-), and three new lemnadiolboursides A-C (-), along with three known lemnaboursides (-). Their structures were elucidated by detailed spectroscopic analysis, ECD analysis, chemical methods, and comparison with the literature data. Lemnadiolboursides A-C (-) contained a lemnal-1(10)-ene-7,12-diol moiety compared with the lemnaboursides. All these compounds were evaluated for antibacterial activity; cell growth inhibition of A549, Hela, HepG2, and CCRF-CEM cancer cell lines; and inhibition of LPS-induced NO production in RAW264.7 macrophages. The results indicated that compounds , , and - exhibited antibacterial activity against and (MIC 4-16 μg/mL); compounds - displayed low cytotoxicity on the CCRF-CEM cell lines (IC 10.44-27.40 µM); and compounds , and showed weak inhibition against LPS-induced NO production (IC 21.56-28.06 μM).
Topics: Animals; Anthozoa; Anti-Bacterial Agents; Antineoplastic Agents; Biological Products; Cell Line, Tumor; Diterpenes; Drug Discovery; Glycosides; Humans; Macrophages
PubMed: 34198505
DOI: 10.3390/md19060339 -
International Journal of Molecular... May 2024The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on...
The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on serum lipids, with a mechanism still not fully clarified. In the present study, the interaction of cafestol and 16--methylcafestol with the stabilized ligand-binding domain (LBD) of the Farnesoid X Receptor was evaluated by fluorescence and circular dichroism. Fluorescence quenching was observed with both cafestol and 16--methylcafestol due to an interaction occurring in the close environment of the tryptophan W454 residue of the protein, as confirmed by docking and molecular dynamics. A conformational change of the protein was also observed by circular dichroism, particularly for cafestol. These results provide evidence at the molecular level of the interactions of FXR with the coffee diterpenes, confirming that cafestol can act as an agonist of FXR, causing an enhancement of the cholesterol level in blood serum.
Topics: Diterpenes; Receptors, Cytoplasmic and Nuclear; Cholesterol; Humans; Coffee; Molecular Docking Simulation; Protein Binding; Molecular Dynamics Simulation; Circular Dichroism
PubMed: 38892285
DOI: 10.3390/ijms25116096 -
Journal of the American Chemical Society Feb 2023The significant structural diversity and potent bioactivity of the fungal indole diterpenes (IDTs) has attracted considerable interest in their biosynthesis. Although...
The significant structural diversity and potent bioactivity of the fungal indole diterpenes (IDTs) has attracted considerable interest in their biosynthesis. Although substantial skeletal diversity is generated by the action of noncanonical terpene cyclases, comparatively little is known about these enzymes, particularly those involved in the generation of the subgroup containing emindole SA and DA, which show alternate terpenoid skeletons. Here, we describe the IDT biosynthetic machinery generating these unusual IDT architectures from and . The function of four putative cyclases was interrogated via heterologous expression. Two specific cyclases were identified that catalyze the formation of epimers emindole SA and DA from and , respectively. These cyclases are both clustered along with all the elements required for basic IDT biosynthesis yet catalyze an unusual Markovnikov-like cyclization cascade with alternate stereochemical control. Their identification reveals that these alternate architectures are not generated by mechanistically sloppy or promiscuous enzymes, but by cyclases capable of delivering precise regio- and stereospecificities.
Topics: Diterpenes; Terpenes; Indoles; Cyclization
PubMed: 36710518
DOI: 10.1021/jacs.2c11170