四种新的二萜托罗酮,salvirrddonesA-D(1-4),和四个新的icetexanes,salvirrddicesA-D(9-12),连同13种新的11,12-seco-norabietane二萜,salvirrddnorA-M(14-24,31,32)和16种已知化合物(5-8,13,25-30,33-37),从板栗的根和根茎中分离出来。tomentosaStib。通过全面的光谱分析阐明了它们的结构,量子化学计算,和X射线晶体学。在结构上,化合物1-8代表一类罕见的天然产物,具有独特的环庚-2,4,6-三烯酮部分和二萜骨架。生物测定显示,只有二萜类托罗酮3、5、6和7对几种人癌细胞系表现出明显的活性,IC50值在3.01至11.63μM范围内。此外,3显示抑制Hep3B细胞增殖,阻断细胞周期的G0/G1期,诱导线粒体功能障碍和氧化应激,促进细胞凋亡,以及在体外抑制迁移和侵袭。同时,3证明了抗增殖,促凋亡,和体内Hep3B异种移植斑马鱼模型中的迁移抑制作用。网络药理学分析和分子对接结果提示3可能通过PI3K-Akt信号通路治疗肝细胞癌,以及通过结合PARP1和CDK2靶标。总的来说,本研究结果极大地扩展了天然产物中的二萜类化合物,并可能为发现新的抗肿瘤药物提供一种新的化学支架。
Four new
diterpenoid tropolones, salvirrddones A-D (1-4), and four new icetexanes, salvirrddices A-D (9-12), along with thirteen new 11,12-seco-norabietane diterpenoids, salvirrddnor A-M (14-24, 31, 32) and sixteen known compounds (5-8, 13, 25-30, 33-37), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Their structures were elucidated by comprehensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Structurally, compounds 1-8 represent a class of rare natural products featuring a unique cyclohepta-2,4,6-trienone moiety with
diterpenoid skeletons. Bioassays showed that only
diterpenoid tropolones 3, 5, 6, and 7 exhibited significant activity against several human cancer cell lines with IC50 values ranging from 3.01 to 11.63 μM. Additionally, 3 was shown to inhibit Hep3B cell proliferation, block the G0/G1 phase of the cell cycle, induce mitochondrial dysfunction and oxidative stress, promote apoptosis, as well as inhibit migration and invasion in vitro. Meanwhile, 3 demonstrated anti-proliferative, pro-apoptotic, and migration-inhibitory effects in the Hep3B xenograft zebrafish model in vivo. Network pharmacological analysis and molecular docking results suggested that 3 may treat hepatocellular carcinoma (HCC) through the PI3K-Akt signaling pathway, as well as by binding PARP1 and CDK2 targets. Overall, the present results extremely expand the repertoire of diterpenoids from natural products and may provide a novel chemical scaffold for the discovery of new antitumor drugs.