Abstract:
An extensive phytochemical investigation on the EtOAc-soluble fraction of the 90% MeOH extract from the twigs and needles of the \'vulnerable\' Chinese endemic conifer Tsuga forrestii (Forrest\'s hemlock) led to the isolation and characterization of 50 structurally diverse diterpenoids, including 15 unreported C-18 carboxylated ones (tsugaforrestiacids A-O, 1-15, resp.). Among them, compounds 1-7 are abieten-18-oic acids, compound 8 is an abieten-18-succinate, and compounds 10-12 are podocarpen-18-oic acids, whereas compounds 13-15 are pimarane-type, isopimarane-type, and totarane-type diterpenoid acids, respectively. Their structures and absolute configurations were determined by a combination of spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) data, and single crystal X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the ATP-citrate lyase (ACL), a key enzyme in cellular metabolism. Tsugaforrestiacids E (5) and H (8) were found to have significant inhibitory effects against ACL, with IC50 values of 5.3 and 6.2 μM, respectively. The interactions of the bioactive molecules with the ACL enzyme were examined by molecular docking studies. The isolated diterpenoids also provide chemotaxonomic evidence to support the delimitation of Tsuga from its closest sister group (Nothotsuga). The above findings highlight the importance of protecting plant species with unique and diverse secondary metabolites, which may be potential sources of new therapeutic agents for the treating ACL-associated diseases.
摘要:
对来自“脆弱的”中国特有针叶树Tsugaforrestii(福雷斯特铁杉)的树枝和针叶的90%MeOH提取物的EtOAc可溶部分进行了广泛的植物化学研究,导致了50种结构多样的二萜化合物的分离和表征,包括15个未报告的C-18羧化的(tsugaforresticidsA-O,1-15,分别。).其中,化合物1-7是松香-18-酸,化合物8是一种abieten-18-琥珀酸盐,化合物10-12是podocarpen-18-oic酸,而化合物13-15是匹马环型,异imarane型,和totarane型二萜酸,分别。它们的结构和绝对构型是通过光谱方法的组合确定的,GIAONMR计算和DP4+概率分析,电子圆二色性(ECD)数据,和单晶X射线衍射分析。评估所有分离株对ATP-柠檬酸裂解酶(ACL)的抑制活性,细胞代谢的关键酶.发现TsugaforrestiacidsE(5)和H(8)对ACL有显著的抑制作用,IC50值为5.3和6.2μM,分别。通过分子对接研究检查生物活性分子与ACL酶的相互作用。分离的二萜化合物还提供了化学分类学证据,以支持Tsuga与其最亲密的姐妹组(Nothotsuga)的划界。上述发现强调了保护具有独特和多样化次生代谢产物的植物物种的重要性。这可能是治疗ACL相关疾病的新治疗剂的潜在来源。