lupane has been researched along with lupeol* in 4 studies
4 other study(ies) available for lupane and lupeol
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[Construction of cell factories for production of lupeol in Saccharomyces cerevisiae].
Lupane-type triterpenoids, such as betulinic acid, are derived from lupeol and have excellent properties in anti-HIV, anti-cancer activities and so on. For realizing heterogenous production of lupane-type triterpenoids, our research firstly integrated all the seven genes in the MVA pathway in Saccharomyces cerevisiae to increase the supply of squalene (triterpenoids universal precursor) in a single step using the DNA assembler method. Next, cell factories for production of lupeol was constructed by integrating Arabidopsis thaliana lupeol synthetic gene (AtLUP) into chromosome of triterpenoid chassis strain. Results showed that the MVA pathway, about 20 kb nucleotide length, could be assembled in one-pot process and the doubled MVA pathway could significantly improve squalene by 500-fold, reaching 354.00 mg•L⁻¹. NK2-LUP was obtained by introducing AtLUP gene on chromosome, and could produce 8.23 mg•L⁻¹ lupeol. This study supports the possibility of large-scale biosynthetic pathway assembly in S.cerevisiae and lays the foundation of obtaining cell factories for production of lupan-type triterpenoids at the same time. Topics: Betulinic Acid; Biosynthetic Pathways; Metabolic Engineering; Pentacyclic Triterpenes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Triterpenes | 2016 |
Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B.
Protein Tyrosine Phosphatase 1B (PTP1B) has been recognized as a promising therapeutic target for treating obesity, diabetes, and certain cancers for over a decade. Previous drug design has focused on inhibitors targeting the active site of PTP1B. However, this has not been successful because the active site is positively charged and conserved among the protein tyrosine phosphatases. Therefore, it is important to develop PTP1B inhibitors with alternative inhibitory strategies. Using computational studies including molecular docking, molecular dynamics simulations, and binding free energy calculations, we found that lupane triterpenes selectively inhibited PTP1B by targeting its more hydrophobic and less conserved allosteric site. These findings were verified using two enzymatic assays. Furthermore, the cell culture studies showed that lupeol and betulinic acid inhibited the PTP1B activity stimulated by TNFα in neurons. Our study indicates that lupane triterpenes are selective PTP1B allosteric inhibitors with significant potential for treating those diseases with elevated PTP1B activity. Topics: Allosteric Regulation; Allosteric Site; Animals; Betulinic Acid; Catalytic Domain; Cell Line; Enzyme Inhibitors; Gene Expression; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; Ligands; Mice; Molecular Docking Simulation; Molecular Dynamics Simulation; Neurons; Pentacyclic Triterpenes; Protein Binding; Protein Domains; Protein Structure, Secondary; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Structural Homology, Protein; Thermodynamics; Triterpenes | 2016 |
Investigation of the interactions of lupane type pentacyclic triterpenes with outer leaflet membrane phospholipids--Langmuir monolayer and synchrotron X-ray scattering study.
Lupane type pentacyclic triterpenes (LTs) are pharmacologically active natural products isolated from different plants. They have broad spectrum of therapeutic action ranging from anticancer via anti-HIV, antibiotic to anti-inflammatory and anti-protozoal activity. Many scientific papers underline that the key stage in the LT mechanism of action is their incorporation into cellular membrane and the interaction with the structural lipids. In our research we apply Langmuir monolayers as a versatile platform for the investigation of these phenomena, since till now important aspects concerning this issue are incomprehensible. We focus our attention on the interactions of lupeol and betulinic acid with choline-headgroup structural lipids: a representative of saturated glycerophosphatidylcholines (DPPCs), and octadecyl-sphingomyelin--a representative of membrane sphingolipids. Application of complementary physicochemical techniques such as the Langmuir technique, Brewster angle microscopy, and grazing incidence X-ray diffraction supported by thermodynamic analysis enabled us to investigate the intermolecular interactions in such binary model systems. Our results corroborate that LT is miscible with the outer leaflet membrane phospholipids, both DPPC and SM in the whole range of mole ratios. Moreover, the introduction of LT into the phospholipid film, even in small proportion, leads to the loss of periodical ordering of the phospholipid molecules and the disappearance of the diffraction signal as observed by GIXD. Our results also proved that LT does not form any surface complexes of fixed stoichiometry resembling the well characterized lipid rafts. Topics: 1,2-Dipalmitoylphosphatidylcholine; Betulinic Acid; Kinetics; Pentacyclic Triterpenes; Scattering, Radiation; Sphingomyelins; Synchrotrons; Thermodynamics; Triterpenes; X-Ray Diffraction; X-Rays | 2012 |
Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents.
The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosides, and alpha-D-arabinosides) were synthesized and in vitro tested for cytotoxicity against three cancerous (A-549, DLD-1, and B16-F1) and one healthy (WS1) cell lines. The addition of a sugar moiety at the C-3 or C-28 position of betulin (2) resulted in a loss of cytotoxicity. In contrast, the 3-O-beta-D-glucosidation of lupeol (1) improved the activity by 7- to 12-fold (IC50 14-15.0 microM). Moreover, the results showed that cancer cell lines are 8- to 12-fold more sensitive to the 3-O-alpha-L-rhamnopyranoside derivative of betulinic acid (IC50 2.6-3.9 microM, 22) than the healthy cells (IC50 31 microM). Thus, this study indicates that 3-O-glycosides of lupane-type triterpenoids represent an interesting class of potent in vitro cytotoxic agents. Topics: Animals; Antineoplastic Agents, Phytogenic; Betula; Betulinic Acid; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Fibroblasts; Glycosides; Humans; Mice; Pentacyclic Triterpenes; Triterpenes | 2006 |