1393477-81-0Relevant articles and documents
NO-releasing enmein-type diterpenoid derivatives with selective antiproliferative activity and effects on apoptosis-related proteins
Li, Dahong,Hu, Xu,Han, Tong,Liao, Jie,Xiao, Wei,Xu, Shengtao,Li, Zhanlin,Wang, Zhenzhong,Hua, Huiming,Xu, Jinyi
, (2016)
: A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a-i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a-i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.
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
supporting information, 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.
Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies
Tang, Weibin,Xie, Jianlin,Xu, Song,Lv, Haining,Lin, Mingbao,Yuan, Shaopeng,Bai, Jinye,Hou, Qi,Yu, Shishan
, p. 7600 - 7612 (2015/01/09)
Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50= 0.067 μM) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 μmol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50> 3852 μmol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.
