New Bicyclo[3.1.0]hexane Unit ent-Kaurane Diterpene and Its seco-Derivative from Isodon eriocalyx var. laxiflora

Wang, Weiguang; Du, Xue; Li, Xiaonian; Wu, Haiyan; Xu, Liang; Shang, Shan‐Zhai; Zhan, Rui; Liang, Cheng-Qin; Kong, Lingmei; Li, Yan; Pu, Jian‐Xin; Sun, Han‐Dong

doi:10.1021/ol203061z

Cited by 36 publications

(20 citation statements)

References 43 publications

(23 reference statements)

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“…Isodon ternifolius (D. Don) Kudô, a prominent species of the Isodon genus, is known for producing bioactive ent-kaurane diterpenoids, 21, 22, 23 and has long been used as folk medicine for the treatment of icterohepatitis, enteritis and other inflammatory conditions. 24 I. ternifolius is also the major ingredient of a Chinese patent medicine ‘FufangSanyexiangchacaiPian', which is used to treat acute and chronic hepatitis and hepatitis B. Longikaurin A (LK-A), shown in Figure 1a, is a major ent-kaurane diterpenoid produced by I. ternifolius .…”

Section: Introductionmentioning

confidence: 99%

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells

Liao

Bai

et al. 2014

Cell Death Dis

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in human HCC cell lines. LK-A also suppressed tumor growth in SMMC-7721 xenograft models, without inducing any notable major organ-related toxicity. LK-A treatment led to reduced expression of the proto-oncogene S phase kinase-associated protein 2 (Skp2) in SMMC-7721 cells. Lower Skp2 levels correlated with increased expression of p21 and p-cdc2 (Try15), and a corresponding decrease in protein levels of Cyclin B1 and cdc2. Overexpression of Skp2 significantly inhibited LK-A-induced cell cycle arrest in SMMC-7721 cells, suggesting that LK-A may target Skp2 to arrest cells at the G2/M phase. LK-A also induced reactive oxygen species (ROS) production and apoptosis in SMMC-7721 cells. LK-A induced phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase and P38 MAP kinase. Treatment with, the JNK inhibitor SP600125 prevented LK-A-induced apoptosis in SMMC-7721 cells. Moreover, the antioxidant N-acetylcysteine prevented phosphorylation of both JNK and c-Jun. Taken together, these data indicate that LK-A induces cell cycle arrest and apoptosis in cancer cells by dampening Skp2 expression, and thereby activating the ROS/JNK/c-Jun signaling pathways. LK-A is therefore a potential lead compound for development of antitumor drugs targeting HCC.

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Section: Introductionmentioning

confidence: 99%

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells

Liao

Bai

et al. 2014

Cell Death Dis

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“…Ent-kaurane diterpenoids are the primary chemical constitutes of Isodon species responsible for the bioactivities of the plants (Wang et al, 2012;Wu et al, 2014;Yang et al, 2016), and the studies herein on I. serra added nine new ones. Among the isolates, two compounds exhibited weak cytotoxicity compared with paclitaxel, as well as a new one that showed remarkable effect against NO production.…”

Section: Discussionmentioning

confidence: 99%

Bioactive ent-kaurane diterpenoids from Isodon serra

et al. 2016

Self Cite

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“…ent -Kaurane diterpenoid derivatives with diverse unique chemical skeletons are generally quite complex, incorporating numbers of intricate ring systems and stereogenic centers, and exhibit promising biological activities [ 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. The preparation of ent -kaurane diterpenoid libraries inevitably involved rather laborious and complex synthetic sequences, especially total synthesis [ 70 , 71 , 72 ].…”

Section: Oridonin As the Lead To Synthesize Ent mentioning

confidence: 99%

Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound

Han

Liao

et al. 2016

IJMS

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Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

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New Bicyclo[3.1.0]hexane Unit ent-Kaurane Diterpene and Its seco-Derivative from Isodon eriocalyx var. laxiflora

Cited by 36 publications

References 43 publications

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells

Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells

Bioactive ent-kaurane diterpenoids from Isodon serra

Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound

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