Sesquiterpenes Germacrene Research Articles

Parthenolide Inhibits Synthesis and Promotes Degradation of Programmed Cell Death Ligand 1 and Enhances T Cell Tumor-Killing Activity.

Parthenolide is a germacrane sesquiterpene lactone separated from the traditional medicinal plant feverfew. Previous studies have shown that parthenolide possesses many pharmacological activities, involving anti-inflammatory and anticancer activities. However, the antitumor mechanism of parthenolide has not been fully elucidated. Thus, we investigate the potential antitumor mechanisms of parthenolactone. We predicted through network pharmacology that parthenolide may target HIF-1α to interfere with the occurrence and development of cancer. We found that parthenolide inhibited PD-L1 protein synthesis through mTOR/p70S6K/4EBP1/eIF4E and RAS/RAF/MEK/MAPK signaling pathways and promoted PD-L1 protein degradation through the lysosomal pathway, thereby inhibiting PD-L1 expression. Immunoprecipitation and Western blotting results demonstrated that parthenolide inhibited PD-L1 expression by suppressing HIF-1α and RAS cooperatively. We further proved that parthenolide inhibited cell proliferation, migration, invasion, and tube formation via down-regulating PD-L1. Moreover, parthenolide increased the effect of T cells to kill tumor cells. In vivo xenograft assays further demonstrated that parthenolide suppressed the growth of tumor xenografts. Collectively, we report for the first time that parthenolide enhanced T cell tumor-killing activity and suppressed cell proliferation, migration, invasion, and tube formation by PD-L1. The current study provides new insight for the development of parthenolide as a novel anticancer drug targeting PD-L1.

Functional characterization of sesquiterpene synthase in Mongolian medicine Syringa oblata in heartwood formation

Lilac (Syringa oblata) is a well-known horticultural plant, and its aromatic heartwood is widely utilized in Traditional Mongolian Medicine for treating angina. However, limited research on the dynamic changes and mechanisms of aromatic substance formation during heartwood development hinders the analysis and utilization of its medicinal components. In this study, volatile metabolome analysis revealed that sesquiterpenes are the primary metabolites responsible for the aroma in heartwood, with cadinane and eremophilane types being the most prevalent. Among the identified sesquiterpene synthases, SoSTPS1-5 exhibited significantly increased expression in heartwood formation and was selected for further investigation. Molecular docking simulations predicted multiple amino acid binding sites and confirmed its ability to catalyze the formation of eremophilane, copaene, cadinane, germacrane, and elemane-type sesquiterpenes from FPP (farnesyl pyrophosphate). Co-expression and promoter analysis suggested a transcriptional regulatory network primarily involving WRKY transcription factors. Additionally, aiotic and biotic stress inducers, such as Ag+, Fusarium oxysporum, and especially MeJA, were found to activate the expression of SoSTPS1-5 and promote sesquiterpene accumulation. This study provides insights into the basis of medicinal substance formation and the potential mechanisms of sesquiterpene accumulation in lilac heartwood, laying a foundation for future research on the biosynthesis and utilization of its medicinal components.

New insights into the chemical composition of essential oils from Phlomis olivieri Benth. shoots

Essential oils from Phlomis olivieri Benth. shoots were phytochemically investigated in order to identify new chemotypes of this plant. The essential oils were obtained by hydrodistillation and analyzed by gas chromatography coupled to mass spectrometry. A quantitative variation in constituents was estimated in essential oils from samples collected in 11 different regions of Hamedan province. The major constituents of the essential oil were the sesquiterpenes germacrene D, (E)-β-caryophyllene and (E)-β-farnesene. Germacrene D ranged from 5.3% to 36.9%, (E)-β-caryophyllene ranged from 6.3% to 61.9%, and (E)-β-farnesene ranged from 5.1% to 18.4%, suggesting the occurrence of three chemotypes.

Phytochemical analysis and antibacterial/antifungal activity of the essential oil of Phlomis olivieri Benth in Iran.

Phlomis olivieri Benth. is an aromatic plant endemic to Iran belonging to the Lamiaceae family. It is used to treat pain, stomach ache and common cold in Iranian traditional medicine. P. olivieri also has valuable biological properties including antioxidant, antimicrobial and analgesic ones. This was the first study designed to assess the quality, quantity and antimicrobial activity of Phlomis olivieri Benth. essential oil (POEO). Samples were randomly collected from flowering twigs of this species in three locations between Azeran and Kamoo in Kashan, Iran at peak flowering in June 2019. Water distillation extraction was used to obtain the POEO the quantity of which was calculated by weight. Gas chromatography coupled to mass spectrometry (GC/MS) was also used for POEO qualitative analysis, which revealed its chemical compounds and their percentages. Antimicrobial activity of POEO was also determined using the agar well diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were also measured using the broth microdilution method. The results of the quantitative and qualitative analysis showed that the POEO yield was ~ 0.2292% and its main chemical compounds included the sesquiterpenes germacrene D (26.43%), β-caryophyllene (20.72%), elixene (6.58%), β-trans-farnesene (6.17%), β-Cyclogermacrane (5.04%), germacrene B (4.73%), α-humulene (4.22%), and monoterpene α-pinene (3.22%). The agar diffusion method demonstrated the highest antimicrobial activity of POEO (MIC ~ 14.50mm) was against the Gram-positive species Streptococcus pyogenes. The POEO also showed the strongest inhibitory and lethal activity against the gram-negative bacterial species Pseudomonas aeruginosa (MIC < 62.50μg/mL) and S. paratyphi-A (MIC < 62.50μg/mL and MBC = 125μg/mL), and fungal species Candida albicans (MIC and MBC = 250μg/mL) as compared to control-positive antibiotics. Therefore, POEO is a valuable natural alternative rich in sesquiterpenes with strong antimicrobial and antifungal activities against some fungal and bacterial strains. It can also be used in the pharmaceutical, food and cosmetic industries.

Germacrane Sesquiterpene Dilactones from Mikania micrantha and Their Antibacterial and Cytotoxic Activity.

Four new germacrane sesquiterpene dilactones, 2β-hydroxyl-11β,13-dihydrodeoxymikanolide (1), 3β-hydroxyl-11β,13-dihydrodeoxymikanolide (2), 1α,3β-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11β,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 μM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.

Bioprospecting the Cerrado’s Aromatic Flora: Chemical and Biological Studies of Three Essential Oils

HIGHLIGHTS The sesquiterpene germacrene D was the major constituent in the three EOs under investigation. EO from Campomanesia adamantium was considered active against Malassezia furfur. All EOs exhibited in vitro anti-inflammatory activity by the chemotaxis model. The most abundant metabolite class of all EOs under study was formed by sesquiterpene hydrocarbons.

Sesquiterpenes from Rhododendron nivale and Their Anti-Inflammatory Activity.

Two new germacrane sesquiterpenes, named nivalenoids A and B (1 and 2), along with four known sesquiterpenes (3-6), were isolated from the Rhododendron nivale. The structures of compounds 1 and 2 were elucidated by integrating spectroscopic analyses, including NMR, UV, IR, as well as HR-MS data. Anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells revealed that compared with the positive control dexamethasone (IC50 =2.50 μM), compounds 1 and 2 showed mild anti-inflammatory activity, with IC50 value of 27.55 μM and 53.26 μM, respectively.

Chemical Composition, Antitumor Potential, and Impact on Redox Homeostasis of the Essential Oils of Orlaya grandiflora from Two Climate Localities

It is well known that abiotic components can affect biosynthetic pathways in the production of certain volatile compounds. The aim of this study was to compare the chemical composition of essential oils obtained from Orlaya grandiflora (L.) Hoffm. collected from two localities in Serbia (continental climate, OG1) and Montenegro (Mediterranean climate, OG2) and to assess their antitumor potential on the human colon cancer HCT-116 and breast cancer MDA-MB-231 cell lines. EOs obtained by hydrodistillation were analyzed using GC-MS and GC-FID methods. The results indicate considerable differences in the chemical compositions of the two samples. Although in both samples the main class of volatiles observed was sesquiterpenes (47.5% for OG1 and 70.1% for OG2), the OG1 sample was characterized by a high amount of monoterpene hydrocarbons (29.3%), and sesquiterpene germacrene D (29.5%) as the most abundant compound. On the other hand, the OG2 sample contained a high quantity of oxygenated sesquiterpenes (20.6%), and β-elemene (22.7%) was the major constituent. The possible antitumor mechanisms of these EOs in the HCT-116 and MDA-MB-231 cell lines were examined by means of cell viability, apoptosis, redox potential, and migratory capacity. The antiviability potential appeared to be dose dependent, since the results showed that both EOs decreased the viability of the tested cells. Stronger antitumor effects were shown in MDA-MB-231 cells after short-term treatment, especially at the highest applied concentration, where the percentage of viability was reduced by over 40%. All tested concentrations of EOs exhibited proapoptotic activity and elevated activity of caspase-3 in a dose- and time-dependent manner. The results also showed decreased concentrations of superoxide anion radical in the treated cells, which indicates their significant antioxidative role. Long-term treatments showed mild recovery effects on cell viability in both cell lines, probably caused by the balancing of redox homeostasis. Elevated levels of nitrites indicate high levels of nitric oxide (NO) production and suggest its higher bioavailability due to the antioxidative environment. The tested EOs also induced a drop in migratory capacity, especially after short-time treatments. Taken together, these results suggest considerable antitumor activity of both EOs, which could have potential therapeutic applications.

A dual-responsive "Yin-Yang" photothermal delivery system to accelerate Parthenolide anti-tumor efficacy.

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.

Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV‑2 papain-like protease.

The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein, but not the Cys-111 at the PLpro catalytic site. Mutation of Cys-191 or Cys-194 reduces the activity of PLpro. Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192, Thr-193, and Gln-231. Furthermore, parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro. These results reveal that parthenolide inhibits PLpro activity by allosteric regulation.

Identification of the sesquiterpene synthase AcTPS1 and high production of (–)-germacrene D in metabolically engineered Saccharomyces cerevisiae

BackgroundThe sesquiterpene germacrene D is a highly promising product due to its wide variety of insecticidal activities and ability to serve as a precursor for many other sesquiterpenes. Biosynthesis of high value compounds through genome mining for synthases and metabolic engineering of microbial factories, especially Saccharomyces cerevisiae, has been proven to be an effective strategy. However, there have been no studies on the de novo synthesis of germacrene D from carbon sources in microbes. Hence, the construction of the S. cerevisiae cell factory to achieve high production of germacrene D is highly desirable.ResultsWe identified five putative sesquiterpene synthases (AcTPS1 to AcTPS5) from Acremonium chrysogenum and the major product of AcTPS1 characterized by in vivo, in vitro reaction and NMR detection was revealed to be (–)-germacrene D. After systematically comparing twenty-one germacrene D synthases, AcTPS1 was found to generate the highest amount of (–)-germacrene D and was integrated into the terpene precursor-enhancing yeast strain, achieving 376.2 mg/L of (–)-germacrene D. Iterative engineering was performed to improve the production of (–)-germacrene D, including increasing the copy numbers of AcTPS1, tHMG1 and ERG20, and downregulating or knocking out other inhibitory factors (such as erg9, rox1, dpp1). Finally, the optimal strain LSc81 achieved 1.94 g/L (–)-germacrene D in shake-flask fermentation and 7.9 g/L (–)-germacrene D in a 5-L bioreactor, which is the highest reported (–)-germacrene D titer achieved to date.ConclusionWe successfully achieved high production of (–)-germacrene D in S. cerevisiae through terpene synthase mining and metabolic engineering, providing an impressive example of microbial overproduction of high-value compounds.

Exploration of essential oil from Psychotria poeppigiana as an anti-hyperalgesic and anti-acetylcholinesterase agent: Chemical composition, biological activity and molecular docking

Ethnopharmacological relevanceLeaves from Psychotria poeppigiana Müll. Arg. (accepted as Palicourea tomentosa (Aubl.) Borhidi), Rubiaceae, has traditionally been used in medicine for treatments of inflammation and pain; Synonymously, Cephaelis elata for the treatment of dementia; However, few scientific studies have been evidence demonstrating this activity. Aim of the studyThe aim of this study was to investigate the chemical composition of P. poeppigiana essential oil obtained from leaves (EOPP) and its antioxidant, anti-inflammatory and acetylcholinesterase (AChE) activities. Molecular docking simulations were carried out with the main constituents. Materials and methodsEOPP (hydrodistillation) was analysed by gas chromatography-mass spectrometry (GC–MS). The fractionation of EOPP afforded germacrene D and bicyclogermacrene. The antioxidant activity of EOPP was determined by MDA assay. The inflammatory parameters were evaluated using CFA model (with paw edema, mechanical, thermal hyperalgesia, MPO and NAG) in EOPP (30, 100 and 300 mg/kg), germacrene D and bicyclogermacrene (30 mg/kg). The AChE inhibition was evaluated in rat brain structures and molecular docking simulations were carried out using Autodock v.4.3.2. ResultsGC-MS analysis identified 19 compounds, and the major compounds were germacrene D (29.38%) and bicyclogermacrene (25.21%). EOPP exhibited high antioxidant capacity (IC50 = 12.78 ± 1.36 μg/mL). All the tested doses of EOPP and both major constituents significantly inhibited cold and mechanical hyperalgesia and significantly blocked the increase in MPO activity 24 h after the CFA injection. There was significant AChE inhibition by EOPP and germacrene D in the cerebral cortex and hippocampus (>50%). Enzyme-ligand molecular modelling showed that the major constituents of EOPP interacted differently with AChE. ConclusionsThe chemical compounds of the essential oil from the leaves of P. poeppigiana is based mainly on terpenes, the sesquiterpenes germacrene D (29.38%) and bicyclogermacrene (25.21%) being the major compounds. EOPP presented antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. Besides, enzyme-ligand molecular modelling showed the EOPP may act as an anti-hyperalgesic and AChE inhibitory agent. Taken together, these results might be in accordance with if folk use for pain- and inflammation-related symptoms.

Five new germacrane sesquiterpenes with anti-inflammatory activity from Salvia petrophila

• Five new germacrane sesquiterpene lactones were isolated from Salvia Petrophila . • These sesquiterpenes are unusual with an endocyclic double bond in the γ-lactone ring. • All new compounds exhibited moderate anti-inflammatory activities in vitro. Five new germacrane sesquiterpene lactones, petrophins A–E ( 1 – 5 ), were isolated from the whole herbs of Salvia petrophila . The structures were established using spectroscopic analysis (1D and 2D NMR, HR-ESI-MS) and compatible with values in the literature. These sesquiterpenes are unusual with an endocyclic double bond in the γ -lactone ring. All the isolated compounds were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macro-phage RAW264.7 cells.

Phytochemical screening and phytocytotoxic effects of the tropical Myrcia vittoriana (Myrtaceae).

We investigated whether essential oil and aqueous and ethanolic extracts from M. vittoriana leaves have phytotoxic effects on the germination and initial development, and cytogenotoxic effects on the cell cycle, of model plants. The essential oil and extracts of M. vittoriana were characterized and used as treatments in phytotoxicity and cytotoxicity tests. The results indicated a reduction in germinative parameters and plant growth, with the higher concentrations of extracts and essential oil having the most evident effects. The cell cycle was also affected with a reduction of the mitotic index and the presence of chromosomal and nuclear alterations. All treatments showed clastogenic and aneugenic modes of action. The results can be associated with the synergistic effects of metabolites found in the extracts and essential oil, mainly the presence of the sesquiterpene germacrene D in the essential oil and of catechins, saponins, and tannins in the extracts. These substances inhibit plant germination and growth, confirming the phytotoxic effects of M. vittoriana in plant models, which should now be tested under field conditions.

Germacrane sesquiterpenes from leaves of Eupatorium chinense inhibit protein tyrosine phosphatase

Three new germacrane-type sesquiterpene lactones (1–3) were isolated alongside seven known related congeners (4–10) from the leaves of Eupatorium chinense L. (Compositae). The planar structures of 1–3 were elucidated by their spectroscopic data, including 1D and 2D NMR spectra. The relative and absolute configurations of 1–3 were determined using NOESY experiments and electronic circular dichroism analyses. Compounds 1, 4, 5, and 7 inhibited protein tyrosine phosphatase (PTP) 1B activity with IC50 values of 25, 11, 28, and 24 μM, respectively. Among these, compound 4 exhibited an inhibitory effect on T-cell PTP (TCPTP) with an IC50 value of 25 μM. To our knowledge, this is the first study demonstrating the PTP inhibitory activity of the germacrane sesquiterpenes. The results show that compound 4 acts as an inhibitor of both PTP1B and TCPTP.

Improved production of germacrene A, a direct precursor of \xdf-elemene, in engineered Saccharomyces cerevisiae by expressing a cyanobacterial germacrene A synthase

BackgroundThe sesquiterpene germacrene A is a direct precursor of ß-elemene that is a major component of the Chinese medicinal herb Curcuma wenyujin with prominent antitumor activity. The microbial platform for germacrene A production was previously established in Saccharomyces cerevisiae using the germacrene A synthase (LTC2) of Lactuca sativa.ResultsWe evaluated the performance of LTC2 (LsGAS) as well as nine other identified or putative germacrene A synthases from different sources for the production of germacrene A. AvGAS, a synthase of Anabaena variabilis, was found to be the most efficient in germacrene A production in yeast. AvGAS expression alone in S. cerevisiae CEN.PK2-1D already resulted in a substantial production of germacrene A while LTC2 expression did not. Further metabolic engineering the yeast using known strategies including overexpression of tHMGR1 and repression of squalene synthesis pathway led to an 11-fold increase in germacrene A production. Site-directed mutagenesis of AvGAS revealed that while changes of several residues located within the active site cavity severely compromised germacrene A production, substitution of Phe23 located on the lateral surface with tryptophan or valine led to a 35.2% and 21.8% increase in germacrene A production, respectively. Finally, the highest production titer of germacrene A reached 309.8 mg/L in shake-flask batch culture.ConclusionsOur study highlights the potential of applying bacterial sesquiterpene synthases with improved performance by mutagenesis engineering in producing germacrene A.

Combinatorial Metabolic Engineering in Saccharomyces cerevisiae for the Enhanced Production of the FPP-Derived Sesquiterpene Germacrene.

Farnesyl diphosphate (FPP)-derived isoprenoids represent a diverse group of plant secondary metabolites with great economic potential. To enable their efficient production in the heterologous host Saccharomyces cerevisiae, we refined a metabolic engineering strategy using the CRISPR/Cas9 system with the aim of increasing the availability of FPP for downstream reactions. The strategy included the overexpression of mevalonate pathway (MVA) genes, the redirection of metabolic flux towards desired product formation and the knockout of genes responsible for competitive reactions. Following the optimisation of culture conditions, the availability of the improved FPP biosynthesis for downstream reactions was demonstrated by the expression of a germacrene synthase from dandelion. Subsequently, biosynthesis of significant amounts of germacrene-A was observed in the most productive strain compared to the wild type. Thus, the presented strategy is an excellent tool to increase FPP-derived isoprenoid biosynthesis in yeast.

Chemical Composition and Immunomodulatory Activity of Hypericum perforatum Essential Oils.

Hypericum L. (Hypericaceae) extracts have been used for their therapeutic effects; however, not much is known about the immunomodulatory activity of essential oils extracted from this plant. We isolated essential oils from the flowers and leaves of H. perforatum and analyzed their chemical composition and innate immunomodulatory activity. Analysis of flower (HEOFl) versus leaf (HEOLv) essential oils using gas chromatography–mass spectrometry revealed that HEOFl was comprised mainly of monoterpenes (52.8%), with an abundance of oxygenated monoterpenes, including cis-p-menth-3-en-1,2-diol (9.1%), α-terpineol (6.1%), terpinen-4-ol (7.4%), and limonen-4-ol (3.2%), whereas the sesquiterpenes were found in trace amounts. In contrast, HEOLv was primarily composed of sesquiterpenes (63.2%), including germacrene D (25.7%) and β-caryophyllene (9.5%). HEOLv also contained oxygenated monoterpenes, including terpinen-4-ol (2.6%), while monoterpene hydrocarbons were found in trace amounts. Both HEOFl and HEOLv inhibited neutrophil Ca2+ mobilization, chemotaxis, and reactive oxygen species (ROS) production, with HEOLv being much more active than HEOFl. Furthermore, the pure sesquiterpenes germacrene D, β-caryophyllene, and α-humulene also inhibited these neutrophil responses, suggesting that these compounds represented the active components of HEOLv. Although reverse pharmacophore mapping suggested that potential protein targets of germacrene D, β-caryophyllene, bicyclogermacrene, and α-humulene could be PIM1 and mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAK2), a kinase binding affinity assay did not support this finding, implying that other biological targets are involved. Our results provide a cellular and molecular basis to explain at least part of the beneficial immunotherapeutic properties of the H. perforatum essential oils.

Cytotoxic isoprenoids from Xanthium strumarium linn.

Background and Objective: Xanthium strumarium is a widespread medicinal plant species; particularly fruits and roots are known for improving memory, voice, and appetite as well as curing of poisonous bites of insects and epilepsy. Materials and Methods: The aerial parts of X. strumarium were extracted with a combination of organic solvents. The exhaustively dried organic extract was fractionated until obtaining pure individuals by employing the appropriate chromatographic techniques. The spectral information obtained from different nuclear magnetic resonance experiments, mass, infrared, and ultraviolet spectra were the keys to elucidate the chemical structures. Results: Nine compounds (1-9) were obtained: a germacrane sesquiterpene (1), five xanthatin-type sesquiterpenoids (5-9) with α-methylene-γ-lactone moiety, including the new one, methoxy xanthanol (9), a benzopyran derivative not previously found in nature 3,4-diepoxy-2,2-dimethyl-2H-1-benzopyran-6-carboxaldehyde (2), and coumarin (3), along with the C-28 steroid campesterol (4). Conclusion: Most of the compounds under the study showed an appreciated cytotoxic activity against HCT116 and HepG2 cancer cell lines.

Advances in chemistry and bioactivity of parthenolide

Review covering up to 07/2019(-)-Parthenolide is a germacrane sesquiterpene lactone, available in ample amounts from the traditional medical plant feverfew (Tanacetum parthenium). Acting as a covalently reactive compound, it displays anti-inflammatory, redox-modulating, and epigenetic activities, as well as selective cytotoxicity towards cancer stem and progenitor cells. Furthermore, parthenolide was found to modulate microtubule dynamics by interfering with the detyrosination of α-tubulin, a specific posttranslational modification of the cytoskeleton. This review interfaces recently achieved parthenolide syntheses with strategies for bioactivity-based derivatization. Furthermore, chemical probe development from parthenolide is discussed, leading to a qualified summary of reported biological activities and implicated or identified targets. Special emphasis is given to parthenolide-induced microtubule modulation and the recently characterized tubulin carboxypeptidase enzymes involved in nerve (re)growth, cardiac muscle cell function, and metastasis development.