Hong-Ping He

Cipadonoid A, a Novel Limonoid with an Unprecedented Skeleton, from Cipadessa cinerasecns

Cipadonoid A ( 1), a novel limonoid with an unprecedented skeleton, was isolated from the leaves of Cipadessa cinerasecns. Its structure and relative configuration were determined by spectroscopic analysis and computer modeling. 1 represents a new type of limonoid, characterized by a rearranged tetrahydropyranyl ring B incorporating usually exocyclic C-30. A possible biosynthetic pathway of 1 was also proposed.

Phragmalin- and mexicanolide-type limonoids from the leaves of Trichilia connaroides.

Phytochemical investigation of the leaves of Trichilia connaroides afforded 12 new limonoids with phragmalin- (1-11) and mexicanolide-type skeletons (12). The structures of these limonoids, including the absolute configuration of 3, were determined by spectroscopic analysis. Compounds 6 and 8 showed moderate cytotoxicity against HL-60 cells.

Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule

Background: Bcl-2-related proteins regulate mitochondrial membrane permeabilization during apoptosis. Results: A natural compound increases Bim/Bcl-2 interaction, permeabilizing the membrane independently of Bax and Bak. Conclusion: Bim converts Bcl-2 to a Bax- or Bak-like molecule. Significance: We revealed a novel apoptotic mechanism that can be explored for developing therapeutics to treat cancers in which dysregulation of Bcl-2 family proteins is common. Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak-independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knock-out murine embryonic fibroblasts and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane; this was accompanied by oligomerization of these proteins and deep embedding of Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane, thereby inducing apoptosis independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics.

Senegalensions A-C, three limonoids from Khaya senegalensis.

NSFC [30830114]; Ministry of Science and Technology [2009CB522300, 2009CB940900]; Young Academic and Technical Leader Raising Foundation of Yunnan Province [2010CI047]

Analysis of mexicanolide- and phragmalin-type limonoids from Heynea trijuga using high-performance liquid chromatography/electrospray tandem mass spectrometry.

RATIONALE Limonoids, a class of tetranortriterpenoids, exhibit various biological effects, including acting as potent antifeedants and insect growth-regulators against various pests. The analysis of phragmalin- and mexicanolide-type limonoids by collision-induced dissociation tandem mass spectrometry (CID-MS/MS) has not been reported. METHODS A high-performance liquid chromatography/electrospray ionization (HPLC/ESI)-MS/MS method was developed to investigate the fragmentation patterns of [M+NH4 ](+) ions for nine reference phragmalin- and mexicanolide-type limonoids. The method was also used in the identification of limonoid compounds in botanic extracts of Heynea trijuga. RESULTS The losses of side chains and the furan part were the major fragmentation patterns. However, there was variation in the relative abundances of product ions resulting from the same fragmentation pathways. A total of 89 phragmalin- and mexicanolide-type limonoids in botanic extracts of Heynea trijuga were detected and 50 of these compounds were identified or tentatively characterized based on elemental constituents, fragmentation pathways, and the profile of the major product ions of reference compounds. In addition, the isomers could be tentatively distinguished. CONCLUSIONS An HPLC/ESI-MS/MS method was developed and could be used to simultaneously identify and screen phragmalin- and mexicanolide-type limonoids in botanic extracts of Heynea trijuga.

Six New O-Terpenoidal Coumarins, Excavacoumarins B-G from Clausena excavata

Six new O-terpenoidal coumarins named excavacoumarins B-G (1-6) were isolated from the aerial part of Clausena excavata collected in Xishuangbanna, Yunnan.

Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70)

The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50=0.68 nmol/mL, SI=33.86), compound 2d (EC50=15 nmol/mL, SI=12) and compound 5 (EC50=33 nmol/mL, SI >10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds.

Anti-HIV active daphnane diterpenoids from Trigonostemon thyrsoideum

Sixteen daphnane diterpenoids, trigothysoids A-P, along with 15 known ones, were isolated from the methanol extract of the twigs and leaves of Trigonostemon thyrsoideum. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The anti-HIV-1 activity of the compounds was also evaluated in vitro, and five compounds demonstrated potent anti-HIV-1 activity, with EC50 values of 0.015-0.001 nM and TI values of 1618-17,619.

Tetranortriterpenoids from Clausena excavata

Five new tetranortriterpenoids, (11beta)-21,23-dihydro-11,21-dihydroxy-23-oxoobacunone (=21,23-dihydro-21-hydroxy-231-oxozapoterin: 2), (11beta)-21,23-dihydro-11,23-dihydroxy-21-oxoobacunone (=21,23-dihydro-23-hydroxy-21-oxozapoterin; 3), (1alpha,11beta)-1,2,21,23-tetrahydro-1,11,23-trihydroxy-21-oxoobacunone (=21,23-dihydro-23-hydroxy-21-oxoclausenarin; 4), (1alpha,11beta)-23-ethoxy-1,2,21,23-tetrahydro-1,11-dihydroxy-21-oxoobacunone (=23-ethoxy-21,23-dihydro-21-oxoclausenarin; 5); (11beta)-1,2,21,23-tetrahydro-11,23-dihydroxy-21-oxoobacunoic acid; 6), were isolated from the aerial part of Clausena excavata BURM. F. (Rutaceae). All compounds possessed 3,4-seco skeletons. Their structures were established by spectroscopic studies. Tetranortriterpenoids with a 4-hydroxybut-2-eno-4-lactone moietv are rarely found in the genus Clausena.

Limonoids from Aphanamixis polystachya and Their Antifeedant Activity

Eight new aphanamixoid-type aphanamixoids (C-J, 1-8) and six new prieurianin-type limonoids, aphanamixoids K-P (9-14), along with 10 known terpenoids were isolated from Aphanamixis polystachya, and their structures were established by spectroscopic data analysis. Among the new limonoids, 13 compounds exhibited antifeedant activity against the generalist Helicoverpa armigera, a plant-feeding insect, at various concentration levels. In particular, compounds 1, 4, and 5 showed potent activities with EC50 values of 0.017, 0.008, and 0.012 μmol/cm(2), respectively. On the basis of a preliminary structure-activity relationship analysis, some potential active sites in the aphanamixoid-type limonoid molecules are proposed.