87936-09-2Relevant academic research and scientific papers
Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates
Xu, Shengtao,Pei, Lingling,Wang, Chengqian,Zhang, Yun-Kai,Li, Dahong,Yao, Hequan,Wu, Xiaoming,Chen, Zhe-Sheng,Sun, Yijun,Xu, Jinyi
, p. 797 - 802 (2014)
A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.
Spirolactone type diterpene spliced hydrogen sulfide donor derivatives as well as preparation method and application thereof
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Paragraph 0013; 0028; 0030, (2020/09/16)
The invention relates to the field of natural medicines and medicinal chemistry, and relates to spirolactone diterpene spliced hydrogen sulfide donor derivatives as well as a preparation method and application thereof. The invention particularly relates to the preparation method of a series of spirolactone type kaurane diterpene hydrogen sulfide donor derivatives with anti-tumor activity and the application of the derivatives in preparation of anti-tumor drugs. The spirolactone type diterpene hydrogen sulfide donor derivatives and the pharmaceutically acceptable salts thereof are represented by a general formula I or II, wherein R is as described in the claims and the specification.
Hydrogen sulfide releasing oridonin derivatives induce apoptosis through extrinsic and intrinsic pathways
Li, Haonan,Mu, Jiahui,Sun, Jianan,Xu, Shengtao,Liu, Weiwei,Xu, Fanxing,Li, Zhanlin,Xu, Jinyi,Hua, Huiming,Li, Dahong
, (2019/12/26)
Hydrogen sulfide (H2S) has been recognized as the third endogenous signaling gasotransmitter following nitric oxide (NO) and carbon monoxide (CO), and exhibits antiproliferative activity against several cancer cells. In order to stably and controllably release H2S, H2S donating compound (ADT-OH) was used in the present study and 18H2S releasing natural ent-kaurane diterpenoid oridonin derivatives were designed and synthesized. Most derivatives showed more potent antiproliferative activities than oridonin against HepG2 and K562 cell lines, while they were lack of sensitivity to HCT-116 and B16 cells. In particular, 12b showed the most potent antiproliferative activities against HepG2, HCT-116 and K562 cells with IC50 values of 2.57, 5.81 and 0.95 μM, respectively. Through cell cycle analysis, 12b caused cell cycle arrest at S phase in K562 cells and G1 phase in HepG2 cells. In Hoechst 33258 staining assay, cell shrinkage and fragmentation of cell nuclei indicated apoptotic morphological changes. Considering the decline of mitochondrial membrane potential and changes in the levels of apoptosis-related proteins, 12b was shown to induce apoptosis through extrinsic and intrinsic apoptosis pathways.
Oridonin derivatives as potential anticancer drug candidates triggering apoptosis through mitochondrial pathway in the liver cancer cells
Luo, Dongdong,Yi, Yujiao,Peng, Kai,Liu, Tangrong,Yang, Jiayu,Liu, Shan,Zhao, Wanzhou,Qu, Xianjun,Yu, Wengong,Gu, Yuchao,Wan, Shengbiao
, p. 365 - 379 (2019/06/17)
The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to en
Hydrogen sulfide donating ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane derivatives: Design, synthesis and antiproliferative properties
Li, Haonan,Gao, Xiang,Huang, Xiaofang,Wang, Xianhua,Xu, Shengtao,Uchita, Takahiro,Gao, Ming,Xu, Jinyi,Hua, Huiming,Li, Dahong
, p. 446 - 457 (2019/06/18)
Motivated by our interest in hydrogen sulfide bio-chemistry and ent-kaurane diterpenoid chemistry, 14 hydrogen sulfide donating derivatives (9, 11a-c, 12a-c, 13, 14, 16a-c and 17a-b) of ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane were designed and synthesized. Four human cancer cell lines (K562, Bel-7402, SGC-7901 and A549) and two normal cell lines (L-02 and PBMC) were selected for antiproliferative assay. Most derivatives showed more potent activities than the lead ent-kaurane oridonin. Among them, compound 12b exhibited the most potent antiproliferative activities, with IC50 values of 1.01, 0.88, 4.36 and 5.21 μM against above human cancer cell lines, respectively. Further apoptosis-related mechanism study indicated that 12b could arrest Bel-7402 cell cycle at G1 phase and induce apoptosis through mitochondria related pathway. Through Western blot assay, 12b was shown to influence the intrinsic pathway by increasing the expression of Bax, cleaved caspase-3, cytochrome c and cleaved PARP, meanwhile suppressing procaspase-3, Bcl-2, Bcl-xL and PARP.
Structural modification of oridonin: Via DAST induced rearrangement
Luo, Dong-Dong,Peng, Kai,Yang, Jia-Yu,Piyachaturawat, Pawinee,Saengsawang, Witchuda,Ao, Lei,Zhao, Wan-Zhou,Tang, Yu,Wan, Sheng-Biao
, p. 29548 - 29554 (2018/09/10)
A simple and efficient protocol was developed for the syntheses of oridonin analogues, i.e. 6,20-epoxy ent-kaurane diterpenoid analogues from oridonin via diethylaminosulfur trifluoride (DAST) promoted rearrangement, most of which exhibited superior anticancer activities compared with their precursor.
VBE oridonin derivative as well as preparation method and application thereof
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Paragraph 0015; 0016, (2017/07/19)
The invention discloses a VBE oridonin derivative or a pharmaceutically acceptable hydrate thereof which includes a stereoisomer or a tautomer thereof. The VBE oridonin derivative has the anticancer effect and better water solubility and can be used for preparing an antitumor drug. The invention discloses a preparation method of the VBE oridonin derivative.
Novel anticancer oridonin derivatives possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Design, synthesis, biological evaluation and nitric oxide release studies
Zhang, Yihua,Xu, Shengtao,Wang, Guangyu,Lin, Yan,Zhang, Yanju,Pei, Lingling,Yao, Hong,Hu, Mei,Qiu, Yangyi,Huang, Zhangjian,Xu, Jinyi
, p. 2795 - 2800 (2016/06/08)
Oridonin (1) is a complex ent-kaurane diterpenoid with unique antitumor profile, which is isolated from Isodon rubescens. In order to develop novel derivatives of oridonin with improved potency, a series of nitric oxide (NO)-releasing oridonin derivatives were synthesized by coupling diazeniumdiolates with oridonin and its semisynthesized analogues. Their in vitro antiproliferative activity, nitric oxide release ability, and preliminary anticancer mechanism were further evaluated. The results displayed that all the target compounds exhibited potent antiproliferative activities, with IC50 values ranging from 1.84 to 17.01 μM. Besides, it was observed that in most cases, the antiproliferative activity correlated well with levels of intracellular NO release. More interestingly, preliminary mechanism studies revealed that the most potent compound 14d induced apoptosis and arrested the cell cycle at the S phase in Bel-7402 cells, which is different from parent compound oridonin. Together, the above promising results warrant the further development of oridonin/NO hybrids as potential antitumor leads.
Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer
Li, Dahong,Han, Tong,Tian, Kangtao,Tang, Shuang,Xu, Shengtao,Hu, Xu,Wang, Lei,Li, Zhanlin,Hua, Huiming,Xu, Jinyi
, p. 4191 - 4196 (2016/08/17)
Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a–f and 15a–f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50of 0.86, 1.74, 1.16 and 3.75?μM, respectively, and could produce high level (above 25?μM) of NO at the time point of 60?min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents.
1-OXO/ACYLATION-14-ACYLATED ORIDONIN DERIVATIVE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
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, (2015/01/06)
The present invention relates to the fields of natural medicine and medicinal chemistry, and more particularly to a 1-oxo/acylated-14-acylated oridonin derivative of a general formula (I) or a pharmaceutically acceptable salt thereof, a method for preparing the compounds, a pharmaceutical composition comprising the compounds, and application thereof in preparation of antitumor drugs.
