Natural Diterpenoid Research Articles

Ponicidin inhibits pro-inflammatory cytokine TNF-α-induced epithelial-mesenchymal transition and metastasis of colorectal cancer cells via suppressing the AKT/GSK-3β/Snail pathway.

Ponicidin (PON), a natural diterpenoid compound, has been shown to exhibit potent anticancer activities in a wide variety of cancers, including colorectal cancer (CRC). Nevertheless, the precise mechanisms underlying the anti-metastasis effect of PON have not yet been completely defined. The present study was designed to uncover the inhibitory effect of PON on epithelial-mesenchymal transition (EMT), migration and invasion of HCT116 cells induced by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in vitro, and liver metastasis in vivo. Briefly, cell proliferation was assessed by Cell Counting Kit-8 assay, followed by wound healing and transwell assays to evaluate cell migration and invasion. The EMT-related molecular markers were determined through quantitative real-time polymerase chain reaction (qPCR), immunofluorescence(IF), western blot (WB), and immunohistochemistry(IHC). Additionally, WB was used to assess the expression of AKT, phosphorylated AKT (p-AKT), GSK-3β, and phosphorylated GSK-3β (p-GSK-3β). As a result, PON could effectively suppress EMT, migration, and invasion in HCT116 cells in vitro, and liver metastasis of HCT116 cells in vivo. Additionally, PON administration also dramatically altered the expression of EMT-associated markers such as E-cadherin, N-cadherin, and Vimentin, and suppressed the expression of p-AKT, p-GSK-3β and transcription factor, Snail in a dose-dependent manner. Moreover, the incidence of liver metastasis in the control group was 100% and although the incidence of liver metastasis did not decrease, the number of metastatic nodules in the livers of each PON dose group decreased by (34 ± 4.2)%, (64 ± 3.6)%, and (76 ± 5.3)%, respectively, compared to the control group. Collectively, these findings indicated that targeting the AKT/GSK-3β/Snail pathway by PON might be a promising treatment for TNF-α-induced EMT and metastasis of CRC.

Bioactive enmein-type 6,7-seco-ent-kaurane diterpenoids: natural products, synthetic derivatives and apoptosis related mechanism.

Diterpenoids are important and widely distributed natural compounds with various biological effects, including antitumor, anti-inflammatory and so on. Great efforts have been put in phytochemistry research on diterpenoids. A number of structural modified derivatives and pharmacophore incorporated hybrids were also designed and synthesized with promising therapeutic effects. Among the hopefuls, enmein-type 6,7-seco-ent-kaurane diterpenoids with unique ring system and stereogenic centers exhibit attractive activities. Based on their lead-like properties, enmein-type diterpenoids are suitable for further medicinal study. The derivatives were biologically evaluated and showed promising activities, which warranted in-depth research for further understanding. In this review, the natural bioactive enmein-type diterpenoids and the synthetic derivatives were comprehensively summarized.

Oridonin Ameliorates Lipopolysaccharide-Induced Endometritis in Mice via Inhibition of the TLR-4/NF-κBpathway.

Endometritis is a health threat to both humans and animals and poses a huge economic burden. Oridonin (Ori) is a natural diterpenoid isolated from the traditional Chinese herb Rabdosiarubescens (R. rubescens) and has multiple health-promoting effects, including antioxidant, anti-inflammatory, and antitumor effects. There is little evidence showing that Ori can effectively treat endometritis, and the relevant mechanisms need to be further clarified. In this study, we investigated the effects of Ori on LPS-induced endometritis in vivo. Additionally, we examined the effects of Ori on LPS-stimulated mouse endometrial epithelial cells (mEECs). The results showed that Ori treatment significantly alleviated LPS-induced endometritis and reduced the activity of myeloperoxidase. ELISA and qPCR results indicated that Ori dose-dependently decreased the expression of TNF-α, IL-1β, and IL-6 both in tissues and in mEECs. In addition, Ori was found to inhibit LPS-induced TLR4/NF-κB signaling pathway activation. These results suggest that Ori effectively attenuates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway and that Ori might be an effective drug for the prevention and treatment of LPS-induced endometritis.

Glaucocalyxin A attenuates angiotensin II-induced cardiac fibrosis in cardiac fibroblasts

Glaucocalyxin A (GLA) is a natural ent-Kaurane diterpenoid that possesses cardioprotective effect. Recently, it has been reported that GLA inhibits liver and pulmonary fibrosis, whereas its role in cardiac fibrosis remains unknown. In the present study, we evaluated the effect of GLA on the pathogenesis of cardiac fibrosis in vitro. The results showed that GLA inhibited angiotensin II (Ang II)-induced proliferation and migration in cardiac fibroblasts (CFs). GLA reduced the expression of alpha-smooth muscle actin (α-SMA) in Ang II-induced CFs, suggesting that GLA prevented the differentiation of CFs to myofibroblasts. Furthermore, the production of extracellular matrix (ECM) components including type I collagen (Col-I) and fibronectin, as well as the matrix metalloproteinases (MMPs) including MMP-2 and MMP-9 were reduced by GLA in Ang II-induced CFs. In addition, GLA prevented the Ang II-induced activation of transforming growth factor beta 1 (TGF-β1)/Smad3 pathway in CFs. Collectively, our results demonstrated that GLA acted as an anti-fibrotic agent in cardiac fibrosis, which might be mediated by the regulation of TGF-β1/Smad3 pathway. GLA might be an attractive candidate for improving the prognosis of acute myocardial infarction (AMI) by controlling the cardiac fibrosis.

DS2, a newly synthetic ent-kaurane diterpenoid analog, inhibits proliferation and migration of human gastric cancer cell

Objective: To investigate the effects and the underlying mechanism of DS2, a newly synthetic analog of natural ent-kaurane diterpenoid, on the proliferation and migration capabilities of human gastric cancer cells. Methods: MTT assay, colony formation assay and flow cytometry were used to measure the effects of DS2 on growth, apoptosis and cell cycle of several human gastric cancer cell lines. The function of DS2 in the migration was further detected by wound healing and transwell assays. The expression of migration related proteins were determined by western blot. Results: DS2 inhibited the growth of MGC-803, SGC-7901 and HGC-27 cells in a dose dependent manner. After treatment of DS2 at a concentration of 6.25 μmol/L for 24 h, the survival rates of MGC-803, SGC-7901 and HGC-27 cells were 53.87±3.05%, 55.91±6.97% and 32.41±2.64%, respectively. However, for the normal gastric epithelial cell GES-1, no obvious growth inhibition was observed. In addition, DS2 caused significant G(2)/M arrest and induced apoptosis in MGC-803 cells. Furthermore, compared with the negative control, the colony formation, wound healing rate as well as the number of migrating cells of MGC-803 were significantly decreased in a dose dependent manner after DS2 treatment. DS2 induced the expression of E-cadherin, whereas β-catenin and N-cadherin levels were downregulated in MGC-803. Conclusion: The new compound DS2 has a strong anti-cancer activity, and this study will help us to design and synthesize better diterpenoids derivatives.

Anti-proliferative Effect of 15,16-Dihydrotanshinone I Through Cell Cycle Arrest and the Regulation of AMP-activated Protein Kinase/Akt/mTOR and Mitogen-activated Protein Kinase Signaling Pathway in Human Hepatocellular Carcinoma Cells.

Background15,16-dihydrotanshinone I (DHTS) is a natural abietane diterpenoid that is mainly found in the roots of Salvia miltiorrhiza Bunge (Labiatae). DHTS exhibits a potential anti-proliferative effect in various human cancer cells. However, the mechanisms of action of DHTS as an anti-cancer agent have not been fully elucidated. Therefore, the present study investigated the anti-cancer effect of DHTS in terms of cell cycle regulation and the regulation of the AMP-activated protein kinase (AMPK)/Akt/mTOR signaling pathway in SK-HEP-1 human hepatocellular carcinoma cells.MethodsThe anti-proliferative effects of DHTS were evaluated by the sulforhodamine B assay in SK-HEP-1 cells. Cell cycle distribution was analyzed by flow cytometry. The elucidation of mechanisms of action such as the AMPK/AKT/mTOR and mitogen-activated protein kinase (MAPK) pathway was assessed by Western blot analysis.ResultsDHTS showed a significant anti-proliferative activity against SK-HEP-1 cells. DHTS induced cell cycle arrest in the G0/G1 phase, which was mediated by downregulation of cyclin D1, cyclin A, cyclin E, CDK4, CDK2, c-Myc and p-Rb expression and with increased expression of the CDK inhibitor p21. DHTS also activated the AMPK signaling. In addition, DHTS downregulated the Akt/mTOR and MAPK signaling pathways.ConclusionsOur results suggest that the anti-proliferative activity of DHTS might be associated with the induction of G0/G1 phase cell cycle arrest and regulation of AMPK/Akt/mTOR and MAPK signaling pathways in SK-HEP-1 cells.

Natural Diterpenoid Isoferritin A (IsoA) Inhibits Glioma Cell Growth and Metastasis via Regulating of TGFβ-Induced EMT Signal Pathway.

BackgroundMalignant glioma is intractable primary brain carcinoma that has a poor survival rate. Natural diterpenoid isoferritin A (IsoA) presents antitumor effects by regulating signal pathways in tumor cells. In the present study we investigated the inhibitory effects of IsoA on glioma cells.Material/MethodsThe potential molecular mechanism of IsoA-mediated glioma cell growth and metastasis were investigated using Western blot, gene knockdown, immunofluorescence, and immunohistochemistry.ResultsResults showed that IsoA significantly inhibits growth and metastasis of glioma cells in multiple preclinical settings. In vitro assay showed that IsoA (4 mg/ml) treatment significantly induced apoptosis of glioma cells. Mechanism analysis demonstrated that IsoA (4 mg/ml) treatment decreased TGFβ and regulated EMT markers expression in glioma cells. Reduced expression of TGFβ in glioma cells was closely correlated with inhibitory effects of IsoA on growth and metastasis of glioma cells. TGFβ overexpression promoted glioma cell growth and invasion. Results also showed that IsoA treatment significantly decreased Fibronectin and Vimentin and increased E-cadherin, while TGFβ overexpression abolished the regulation mediated by IsoA in glioma cells. In vivo assay showed that IsoA treatment inhibited tumor growth in a glioma-bearing mouse model.ConclusionsResults indicate that IsoA could be regarded as a potential anti-cancer agent by regulating TGFβ-induced EMT signal pathway.

Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud.

Euphorbia fischeriana Steud is an essential oriental folk medicine used for healing cancer, edema and tuberculosis. Recently, its anticancer activitity has attracted more attention. A volume of research has indicated that diterpenoids are the major anticancer active constituents from this medicinal herb. In this review, we aimed to provide a summary of the promising anticancer diterpenoids from this plant; many diterpenoids mentioned in this article are newly discovered diterpenoids. According to the carbon skeleton and substituents, they can be classified into eight subtypes: ent-abietane, daphnane, tigliane, ingenane, ent-atisane, ent-rosane, ent-kaurane, and lathyrane. Futhermore, their key anticancer mechanisms and protein targets of these compounds will be discussed. These natural diterpenoids could provide a reservoir for drug discovery.

A photochemical approach for evaluating the reactivity of substituted lappaconitines

Lappaconitine (LC) is a natural diterpenoid alkaloid (DTA), acting as a human heart sodium channel blocker and possessing a wide range of biological activities, the cellular and molecular mechanisms of which are widely studied. This interest is due to the fact that various representatives of this DTA class show opposite biological activities. The possible reasons for this difference seem to be related to the peculiarities of the substituent effect on the drug-receptor binding process. In this work, the influence of substituents on the reactivity of LC and its derivatives has been studied by using elementary processes of photodecomposition. The given approach includes the joint analysis of the photophysical properties of the studied systems and their photodecomposition quantum yields. It allows us to trace the influence of substituents, located in the diterpenoid skeleton and anthranilic fragment, on processes in both moieties of LC. Summarizing the data obtained, an inverse dependence of fluorescence and photodegradation quantum yields has been observed. This correlation established for LCs, in particular, allows one to propose a way to evaluate the photostability of potential drugs based on fluorescence analysis. This would be appropriate for compounds in which the reactivity depends on intersystem crossing, i.e. in the cases where the initial and reacting excited states differ in multiplicity.

Functional roles of eriocalyxin B in zebrafish revealed by transcriptome analysis.

Eriocalyxin B (EriB) is a natural ent-kaurane diterpenoid obtained from Isodon eriocalyx var. laxiflora (family Lamiaceae), which has multiple biological activities (e.g. anti-tumor and anti-inflammatory) via the alteration of gene expression and signaling transduction. Recently, RNA sequencing (RNA-seq) has been developed as a dynamic transcriptome approach to analyze the transcriptional profile and in addition use such gene expression profiles to identify novel candidate genes in a zebrafish model. In the present study, a transcriptome analysis was performed to identify differentially expressed genes (DEGs) in an EriB-exposed zebrafish model. RNA sequencing was conducted on zebrafish embryos after EriB (10 μM and 15 μM) treatment for 72 h. A total of 1570 (405 up-regulated and 1165 down-regulated) and 2511 genes (543 up-regulated and 1968 down-regulated) were identified in the 10 μM and 15 μM groups, respectively. Gene ontology analysis was then performed to elucidate the mechanism of action and effects of EriB. We found that 4 pathways were significantly enriched, which include glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, tight junctions, and phototransduction. The critical transcriptional regulators for the DEGs were also identified by Ingenuity Pathway Analysis after the construction of a protein-protein network, which involves p53, c-myc, binding transcription factor 2, sterol regulatory element binding transcription factor 2, nuclear factor erythroid 2 like 2, and interferon regulatory factor 3. In summary, this is the first study to comprehensively explore the effects of EriB in a zebrafish model using a transcriptome analysis approach. Several important genes with substantial changes in expression levels were discovered. The results of this study will provide insights for the future investigation on the biological activities or toxic effects of EriB.

In vitro antipsoriatic activity and mechanism of action of semisynthetic andrographolide compounds

In vitro antipsoriatic activity and mechanism of action of semisynthetic andrographolide compounds

Ovatodiolide targets chronic myeloid leukemia stem cells by epigenetically upregulating hsa-miR-155, suppressing the BCR-ABL fusion gene and dysregulating the PI3K/AKT/mTOR pathway.

Chronic myeloid leukemia (CML) is a myeloproliferative pathology, originating from the hematopoietic cancer stem cells (hCSCs) due to the Bcl-Abl Philadelphia chromosome transformation. However, targeting these hCSCs as an effective anti-CML strategy is relatively less explored. Ovatodiolide (Ova) is a natural diterpenoid isolate of Anisomeles indica with broad anticancer activity. In this study, we investigated the anti-hCSCs potential of Ova against CD34+/CD38−, CD34+/CD38+, and unsorted K562 cell lines using flow cytometry, western blot, RT-PCR, genomic mapping, and tumorsphere formation assays. We demonstrated that compared to unsorted K562 and CD34+/CD38+, CD34+/CD38− cells were significantly enriched with Oct4, Sox2, CD133, Bcr-Abl, p-CrkL and p-Stat5 protein and/or mRNA. Furthermore, we showed that Ova alone or by enhancing the therapeutic potential of Imatinib, reduced the viability of CML cell lines, dose-dependently, irrespective of the cancer stemness, as well as markedly inhibit the Bcr-Abl, p-CrkL, Stat5, and MDR protein expression levels in CD34+ cells. Mechanistic investigations revealed a significant up-regulation of hsa-miR-155, which resulted in the reduction of dysregulating the PIK3CA expression in Ova-treated K562 CD34+/CD38− cells. Additionally, Ova alone or in combination with Imatinib suppressed the hCSC traits of the CD34+/CD38− cells, resulting in loss of their ability to form tumorspheres, enhanced apoptosis, increase in the Bax/Bcl-2 ratio, and dysregulation of the PI3K/AKT/mTOR signaling pathway. Together, these results demonstrate the PI3K/AKT/mTOR signaling-mediated anti-hCSC effect of Ova in CML, as well as suggest a likely role for Ova as a small molecule PI3K/mTOR dual inhibitor, thus, extending its potential benefit to other mTOR-mediated pathologies.

Physiological and Biochemical Indicators of Growth Promoting Effect of Caliterpenone on Mentha arvensis

Mentha arvensis is an herbaceous, edible plant with strong aromatic and medicinal property. An experiment was conducted to investigate the physiological and biochemical changes associated with possible growth promoting effect of caliterpenone on Mentha arvensis. After 45 days of 0.01 mM caliterpenone spray treatment fresh aerial leaves were used for assessment of various parameters. Significant increase was seen in chlorophyll content (P ≤ 0.05), total sugar content (P ≤ 0.05), soluble and bound protein content, moisture content (P ≤ 0.05), specific activity of invertase enzyme along with phenotypic growth features (P ≤ 0.01) after caliterpenone treatment. In light of the present findings study concludes that caliterpenone, a natural phyllocladane diterpenoid isolated from the leaves of Callicarpa macrophylla is a natural, efficient and economic plant growth promoter, which significantly promotes the plant growth without any additional chemical load on soil.

Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX.

Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has displayed beneficial biological activities, including anti-proliferation and anti-angiogenesis effects, in various types of cancers. However, the anti-cancer potential of oridonin and its mechanism in oral cancer have never previously been studied. In this study, we assessed the role of oridonin as an inducer of apoptosis in HSC-3 and HSC-4 human oral cancer cells. Our results showed that oridonin reduces the viability of human oral cancer cells and significantly increases the expression of γH2AX, a well-known marker of DNA damage. 4',6-Diamidino-2-phenylindole (DAPI) staining and western blotting showed that oridonin causes nuclear condensation and fragmentation, and induces cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, oridonin-induced γH2AX accumulation was partially abrogated by Z-VAD, a pan-caspase inhibitor. Taken together, our results suggest that oridonin can effectively induce apoptosis by augmenting the expression of γH2AX in response to DNA damage and might be a promising anti-cancer drug candidate for the treatment of oral cancer.

Sulfated neo-clerodane diterpenoids and triterpenoid saponins from Sheareria nana S. Moore

Three novel neo-clerodane diterpenoids Sheareria A–C (1–3) together with three known triterpenoid saponins were isolated from the whole herb of Sheareria nana S. Moore. Their structures were established by spectroscopic and chemical method. This is the first natural sulfated neo-clerodane diterpenoids. This is the first report of all these compounds from this plant. These neo-clerodane diterpenoids and triterpenoid saponins from S. nana S. Moore may be considered as chemotaxonomic markers for the genus. The compounds isolated were evaluated for their cytotoxic effects against three cancer cell lines, the test substances demonstrated selectivity toward the cancer cells. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from S. nana S. Moore.

Rosoloactone: A natural diterpenoid inducing apoptosis in human cervical cancer cells through endoplasmic reticulum stress and mitochondrial damage

Natural diterpenoids have been previously reported to induce tumor cell apoptosis. We identified a diterpenoid metabolite as rosoloactone that was isolated from the endophytic fungus Trichothecium roseum and displayed significant antitumor activity in vitro. In this study, we report the antitumor effect of rosoloactone on human cervical cancer HeLa cells and its mechanism of action. Our data indicate that rosoloactone induces strong anti-proliferative and pro-apoptotic effects in human cervical cancer HeLa cells, leads to significant apoptotic morphological characteristics, and increases the number of Annexin V-positive stained cells. These effects were associated with endoplasmic reticulum stress (ERS) and mitochondrial damage. More specifically, rosoloactone caused accumulation of misfolded or unfolded proteins in the ER lumen, leading to excessive ERS, as well as mitochondrial damage followed by release of cytochrome c into the cytosol, activation of caspase-9 and −3, and subsequent activation of mitochondria-mediated apoptosis. Furthermore, the effects of rosoloactone were likely accompanied by marked reactive oxygen species (ROS) production. Altogether our results showed that rosoloactone mediates pro-apoptotic effects in human cervical cancer HeLa cells likely via the activation of ERS-associated apoptosis and the mitochondria-mediated apoptotic pathway.

Eriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer

Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid presented in the plant Isodon eriocalyx var. laxiflora, has been reported to diminish angiogenesis-dependent breast tumor growth. In the present study, the effects of EriB on human breast cancer and its underlying mechanisms were further investigated. The in vitro anti-breast cancer activity of EriB was determined using MCF-7 and MDA-MB-231 cell lines. MDA-MB-231 xenograft model of human breast cancer was also established to explore the anti-tumor effect in vivo.We found that EriB was able to induce apoptosis accompanied by the activation of autophagy, which was evidenced by the increased accumulation of autophagosomes, acidic vesicular organelles formation, the microtubule-associated protein 1A/1B-light chain 3B-II (LC3B-II) conversion from LC3B-I and p62 degradation. Meanwhile, EriB treatment time-dependently decreased the phosphorylation of Akt, mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70S6K), leading to the inhibition of Akt/mTOR/p70S6K signaling pathway. Moreover, the blockage of autophagy obviously sensitized EriB-induced cell death, which suggested the cytoprotective function of autophagy in both MCF-7 and MDA-MB-231 cells. Interestingly, the autophagic features and apoptosis induction were prevented by reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine, indicating that ROS played an essential role in the mediation of EriB-induced cell death. Furthermore, in MDA-MB-231 xenograft model, EriB displayed a significant anti-tumor effect via the activation of autophagy and apoptosis in breast tumor cells. Taken together, our findings firstly demonstrated that EriB suppressed breast cancer cells growth both in vitro and in vivo, and thus could be developed as a promising anti-breast tumor agent.

Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells.

Gastric cancer is the third most frequent cause of cancer-associated mortality and almost all patients who respond initially to cisplatin (DDP) later develop drug resistance, indicating multi-drug resistance (MDR) is an essential aspect of the failure of treatment. The natural diterpenoid component Oridonin (Ori) has exhibited efficient inhibition in several types of human cancer. However, the effect and potential mechanism of Ori-reversed MDR in human gastric cancer has not been fully elucidated. In the present study, it was found that Ori significantly suppressed DDP-resistant human SGC7901/DDP cell proliferation, growth and colony formation, causing increased caspase-dependent apoptosis, decreased expression of P-glycoprotein (P-gp), encoded by the MDR gene, multi-drug resistance-associated protein (MRP1), and cyclin D1. SGC7901/DDP cells were cultured with different groups of drugs (Ori, DDP alone, or the combination of Ori and DDP). The drug sensitivity, cell apoptosis and effects on MDR were detected by MTT assay and western blot analysis. The results revealed that Ori is able to reverse the DDP resistance and has a clear synergistic effect with DDP in SGC7901/DDP cells by decreasing the levels of P-gp, MRP1, cyclin D1 and cancerous inhibitor of protein phosphatase 2A. Thus, Ori may be a novel effective candidate to treat DDP-resistant human gastric cancer cells.

Synergistic suppression of t(8;21)-positive leukemia cell growth by combining oridonin and MAPK1/ERK2 inhibitors.

One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways. Here we used a combination of oridonin (natural tetracycline diterpenoid), which has been shown to exhibit anti-RUNX1-ETO activity, and ERK2 kinase inhibitors. We found that treatment of leukemic t(8;21)-positive Kasumi-1 cells with oridonin cause decrease of phosphorylated ERK1/2. Treatment of these cells with ERK2 inhibitors makes them more sensitive to RUNX1-ETO inhibition with oridonin. Therefore we postulate that simultaneous inhibition of RUNX1-ETO and ERK2 cause synergistic effect on survival of leukemic cells.

Five New C19‐Diterpenoid Alkaloids from Delphinium tianshanicum W.T.Wang

Five new diterpenoid alkaloids, tianshanitines A-E (1-5), along with ten known compounds (6-15), were isolated from the EtOH extracts of the whole plant of Delphinium tianshanicum W.T.Wang. Their structures were determined based on extensive spectroscopic analyses, including 1D- and 2D-NMR, HR-ESI-MS, and the structure of tianshanitine C (3) was confirmed by X-ray diffraction analysis. Tianshanitine A (1) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C(1) position. Tianshanitine B (2) is a rare natural diterpenoid alkaloid bearing a OH group at C(16) position. Compounds 1-5, 6, 8, 10, 12 and 14 were evaluated for cytotoxicity against HCT116, MCF-7 and HepG2 human cancer cell lines.