Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXXVI. Tsugaforrestiacids A–O: Structurally diverse C-18 carboxylated diterpenoids from the twigs and needles of the ‘vulnerable’ conifer Tsuga forrestii and their inhibitory effects on ATP-citrate lyase
Peng-Jun Zhou , Ze-Yu Zhao , Jin-Xin Zhu , Yi Zang , Menny M. Benjamin , Juan Xiong , Jia Li , Jin-Feng Hu
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引用次数: 0
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.
期刊介绍:
Phytochemistry is a leading international journal publishing studies of plant chemistry, biochemistry, molecular biology and genetics, structure and bioactivities of phytochemicals, including ''-omics'' and bioinformatics/computational biology approaches. Phytochemistry is a primary source for papers dealing with phytochemicals, especially reports concerning their biosynthesis, regulation, and biological properties both in planta and as bioactive principles. Articles are published online as soon as possible as Articles-in-Press and in 12 volumes per year. Occasional topic-focussed special issues are published composed of papers from invited authors.