Fischerisin A and B, Cytotoxic Sesquiterpenoid-Geranylhydroquinones from Ligularia fischeri

Abstract

NoteSesquiterpenoids are the characteristic secondary metabolites of the Asteraceae family.1) Some of them showed a wide range of biological and pharmacological properties including insect antifeedant,2) anti-inflammatory activity, 3) antibacterial activity, 4) antimalarial activity, 5) cytotoxicity, 6) and nuclear factor kB (NF-kB) inhibition activity 7) etc. The investigation of the structure diversities, structure-activity relationships and biosynthetic approaches of the sesquiterpenoid constitutes in traditional Chinese medicines to screen for cytotoxic leads to drug has been the principal subject of our researchs. 8,9) Ligularia fischeri (LEDEB.) TURCZ. (Asteraceae) has long been used as a folk medicine in China for the treatment of coughs, inflammations, jaundice, scarlet fever, rheumatoidal arthritis, and hepatic diseases.10) In the mid1970s, Japanese researchers initially isolated furanoeremophilane-type sesquiterpenoids from this plant for the first time.11) Subsequent phytochemical researches of this plant collected in different region have resulted in the isolation of many eremophilane-type lactones and norsesquiterpene derivatives. [12][13][14] Recently, we reported the structures of eremophilane dimers and an eremophilane lactam from this plant. 15,16) This paper describes the isolation and structure elucidation of two sesquiterpenoid-geranylhydroquinone hybrids, namely fischerisin A (1) and fischerisin B (2), isolated from the roots of L. fischeri. To the best of our knowledge, these two compounds represent a kind of unprecedented sesquiterpenoid derivative. In addition, the in vitro cytotoxicity of both compounds against cultured human oral epidermoid carcinoma (KB) and human breast cancer (MCF-7) cell lines was also evaluated. Results and DiscussionThe petroleum ether (60-90°C)-Et 2 O-CH 3 OH (1 : 1 : 1) extract of the root of L. fischeri was chromatographed on a silica gel column with a gradient of hexane-acetone as eluent. After the sequential purification, fischerisin A (1) and fischerisin B (2) were finally obtained from the part of hexane-acetone (10 : 1).Fischerisin A (1) During the course of screening natural sesquiterpenoids for new antitumor agents, two novel compounds, fischerisin A (1) and fischerisin B (2), were isolated from the roots of Ligularia fischeri. Their structures were elucidated by interpretation of their IR, high resolution-mass spectrometry (HR-MS), 1D-and 2D-NMR data. Fischerisin A and B are the first representatives of a novel sesquiterpenoid-geranylhydroquinone hybrid, and both compounds exhibited in vitro cytotoxicity against cultured human oral epidermoid carcinoma (KB) and human breast cancer (MCF-7) cell lines with IC 50 values of 9.7 and 10.2 m mM, and 9.8 and 17.8 m mM, respectively.

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression

“…Previous investigations demonstrate that the extracts and biologically active components of LF exert anti-inflammatory, anti-oxidative, anti-hepatotoxic and anti-obesity activities (24)(25)(26)(27)(28)(29). In addition, several studies show the anticancer activity of LF against various cancer cell lines including acute promyelocytic leukemia, oral cancer, breast cancer, lung cancer and ovarian cancer cells (30)(31)(32)(33). However, the biological effects of LF on angiogenesis associated with cancer growth and progression have not yet been explored.…”

Representatives of the genus Ligularia Cass. in the biocollection of the botanical garden VILAR

“…В научной медицине полнее всего исследован Бузульник Фишера. У этанольного экстракта и отдельных компонентов in vitro были выявлены антимутагенная и антигенотоксическая активность (An et al, 2014), цитотоксический эффект в отношении клеточных линий рака полости рта и рака молочной железы человека (Xie et al, 2011), этанольный экстракт рекомендован к изучению как потенциальное средство для лечения и профилактики заболеваний, связанных с ангиогенезом, включая рак (Kim et al, 2015). Извлечения из листьев обладают выраженным антиоксидантным эффектом (Shang et al, 2010;Rekha et al, 2015).…”

Linderalides A–D, Disesquiterpenoid–Geranylbenzofuranone Conjugates from Lindera aggregata

“…Their fascinating structures and important biological activities have attracted great interests of both natural product and synthetic chemists. 1 In recent years, natural conjugates containing the sesquiterpenoid unit, such as sesquiterpenoid−chalcone, 2 sesquiterpenoid−alkaloid, 3 sesquiterpenoid−normonoterpene, 4 sesquiterpenoid−geranylhydroquinone hybrids, 5 and disesquiterpenoid−phenylpropanoid hybrids 6 have been reported. Lindera aggregata (Sims) Kosterm is an important medicinal plant and widely distributed in China.…”