Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Steroids. 2020 Dec;164:108749. doi: 10.1016/j.steroids.2020.108749. Epub 2020 Oct 13.
A series of cinobufagin-3-yl nitrogen-containing-carbamate derivatives were designed, synthesized, and evaluated for their proliferation inhibition activities. The structure-activity relationships suggested that the substituents at C-16 was a crucial factor for the potency and that follows this trends: acetic ester ≫ benzoic ester ≈ hydroxy > carbamate. Compounds 3f, 3g, 3h, and 3i exhibited significant in vitro antiproliferative activities against the eight tested tumor cell lines, with IC values ranging from 8.1 to 237.4 nM. Furthermore, 3g tartrate (3g-TA) significantly inhibited tumor growth by 64.5%, 83.9%, and 93.0% at a doses of 4, 6, 8 mg/kg/qod by ip, respectively.
设计、合成了一系列华蟾毒精-3-基氨基甲酸酯衍生物，并对其增殖抑制活性进行了评价。构效关系表明，C-16 位的取代基是影响活性的关键因素，其趋势为：乙酸酯≫苯甲酸酯≈羟基>氨基甲酸酯。化合物 3f、3g、3h 和 3i 对 8 种测试的肿瘤细胞系表现出显著的体外抗增殖活性，IC 值范围为 8.1 至 237.4 nM。此外，3g 酒石酸盐（3g-TA）以 4、6、8 mg/kg/qod 的剂量腹腔注射给药时，分别显著抑制肿瘤生长 64.5%、83.9%和 93.0%。
