A new cytotoxic caged polyprenylated xanthone from the resin of Garcinia hanburyi

A new caged polyprenylated xanthone, gambogic aldehyde （1）, was isolated from the resin of Garcinia hanburyi. Its structure was elucidated on the basis of spectral data including 1D and 2D NMR data. In addition, the antiproliferative ability of compound 1 was determined in mouse leukemia P388 and P388/ADR cells.

Carascynol A,a hybrid of caryophyllane-type terpenoid and a C6 unit degraded by polyprenylated acylphloroglucinols from Hypericum ascyron

Carascynol A,an unprecedented 4/9/8 ring system hybrid with a peroxide bridge,was characterized from Hyperi-cum ascyron.The architecture contains a caryophyllane-type moiety and a C_(6) unit derived from polyprenylated acylphloroglucinols.Its structure and absolute configuration were determined by comprehensive spectroscopic and X-ray diffraction data.Biologically,compound 1 inhibited cell proliferation in LoVo,SW480,and HCT116 cell lines(IC_(50)=12.30-24.57μM).

Anticancer Properties and Mechanism of Action of Oblongifolin C,Guttiferone K and Related Polyprenylated Acylphloroglucinols

Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.

Hyparillums A and B: polycyclic polyprenylated acylphloroglucinols from Hypericum patulum

Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.

Polyprenylated acylphloroglucinols from the fruits of Hypericum henryi

Hyphenrones R–X(1–7), seven new polyprenylated acylphloroglucinols derivatives, were isolated from the fruits of Hypericum henryi, together with eight know analogues. Compounds 1 and 2 were elucidated to possess complex caged skeleton, while compounds 3–6 shared a common 3,9-epoxy moiety deriving from the normal polyprenylated acylphloroglucinols with a bicyclo[3.3.1]nonane-2,4,9-trione core. The new structures were elucidated on the basis of the interpretation of nuclear magnetic resonance(NMR) data, circular dichroism(CD) comparison, and single-crystal X-ray diffraction. In the bioassay, several compounds exhibited inhibitory activities against human tumor cell lines in vitro.

Type B polycyclic polyprenylated acylphloroglucinols from the roots of Hypericum beanii

Two new type B polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2)and a known biogenetic precursor hyperbeanol Q(3)were isolated from the root extract of Hypericum beanii,a medicinal plant widespread in southwest China.Their chemical structures were elucidated by 1 D/2 D NMR and HRESIMS data analysis,and absolute configurations were determined through detailed electric circular dichroism(ECD)analysis including ECD exciton chirality,Mo2(OAc)4-induced ECD,and ECD comparison.Of these compounds,hyperbeone A(1)is a typical[3.3.1]-type B PPAP with an unusual C-1 geranyl side chain,and hyperberin C(2)possesses a rare bicyclo[5.3.1]hendecane core.Taking compound 3 as a starting point,a plausible biosynthetic pathway to the bicyclic type B frameworks of 1 and 2 was proposed.

Spirohypertones A and B as potent antipsoriatics:Tumor necrosis factor-αinhibitors with unprecedented chemical architectures

Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons,were isolated from Hypericum patulum.The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis,single-crystal X-ray diffraction and electronic circular dichroism calculations.Importantly,2 showed remarkable TNF-αinhibitory activity,which could protect L929 cells from death induced by co-incubation with TNF-αand actinomycin D.It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α.Notably,in an imiquimod-induced psoriasis murine model,2 restrained symptoms of epidermal hyperplasia associated with psoriasis,presenting anti-inflammatory and antiproliferative effects.This discovery positions 2 as a potent TNF-αinhibitor,providing a promising lead compound for developing an antipsoriatic agent.