87936-09-2Relevant articles and documents
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.
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.
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.
