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.

Dearomatized Isoprenylated Acylphloroglucinol Derivatives with Potential Antitumor Activities from Hypericum henryi

A series of dearomatized isoprenylated acylphloroglucinols derivatives,hyperhenols A-E(1-5),as well as seven known analogues(6-12),were characterized from Hypericum henryi.Their structures were determined by combination of NMR,ECD spectroscopy,and X-ray difraction analysis.Compounds 1 and 6-8 were tested to exhibit potential antitumor properties,of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest.In addition,these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines,as well as suppress lung cancer A549 cells metastasis in vitro.

Hypercohones A-C,acylphloroglucinol derivatives with homo-adamantane cores from Hypericum cohaerens

Three new homo-adamantanyl type natural products were derived from polyprenylated polycyclic acylphloroglucinol.Hypercohones A-C(1-3),along with five other known hypercohones(4-8),were isolated from the aerial parts of Hypericum cohaerens.The structures of 1-3 were elucidated on the basis of comprehensive spectroscopic analysis.The inhibitory activities of these isolates against five human cancer cell lines in vitro were tested.

Hypercohones D–G,New Polycyclic Polyprenylated Acylphloroglucinol Type Natural Products from Hypericum cohaerens

Four new polycyclic polyprenylated acylphloroglucinol type metabolites,hypercohones D–G(1–4),along with four known analogues(5–8),were isolated from the aerial parts of Hypericum cohaerens.The structures of these isolates were elucidated by extensive spectroscopic methods.The inhibitory activities of these isolates against five human cancer cell lines in vitro were also tested.

Diverse Polyphenols from Hypericum faberi

Six new polyphenols with diferent isoprenylated xanthones,isoprenylated acylphloroglucinols,and chromone architectures,hyperfaberols A-F(1-6),were isolated from the whole plants of Hypericum faberi along with seven other related known compounds.In which hyperfaberols A/B(1/2)and 12-13 were isoprenylated xanthones,hyperfaberols C-E(3-5)and 8-11 were seven isoprenylated acylphloroglucinol derivatives,while 6-7 were two chromones.Their structures were elucidated by comprehensive analysis of their spectroscopic data as well as detailed comparison with the literature data.Compounds 1 and 11 showed cytotoxities against the human esophageal cancer cell line(ECA-109)and the pancreatic tumor cell line(PANC-1)in vitro,respectively.

Antibacterial Activity of Acylglucinol Derivatives against Flavobacterium columnare

Columnaris (caused by Flavobacterium columnare) is one of the most common bacterial diseases affecting the pond-raised channel catfish (Ictalurus punctatus) in the southeastern United States of America resulting in annual losses of millions of dollars. As part of our continuing effort to discover environmentally benign compounds for the control of columnaris disease, acyl derivatives of phloroglucinol were synthesized and tested against F. columnare using a rapid bioassay. Among the analogs that were tested, diacyl analogs showed very high antibacterial activity against F. columnare in the laboratory bioassay. Diisovaleryl and diisobutyryl analogs were found to have the strongest activity against F. columnare (isolate ALM-00-173) based on 24-h 50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC). Diisovaleryl and diisobutyryl analogs had IC50 values 0.82 mg/L and 0.80 mg/L, respectively, whereas the drug control florfenicol had an IC50 value of 0.81 mg/L. Diisovaleryl and diisobutyryl analogs also had 24-h relative-to- drug-control IC50 values around 1.0 indicating activities similar to florfenicol, which is included in medicated feed and is one of the current management approach for columnaris.

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.

Chemical Constituents from Hypericum beanii

Objective To study the chemical constituents from the aerial parts of Hypericum beani/. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E （1）, （E）-Iinalool-l-oic acid （2）, （4S,5R）-5-（4＇-methyl-3＇-pentenyl）-4-hydroxy-5-methyl- dihydrofuran-2-one （3）, benzoic acid （4）, 4-（3-O-3＂）-3＂-methylbutenyl-6-phenyl- pyran-2-one （5）, 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxJn-2（3H）- one （6）, isoimperatorin （7）, 2,3-dimethoxyxanthone （8）, 3,4-dihydroxy-2- methoxyxanthone （9）, osajaxanthone （10）, nigrolineaxanthone F （1 1）, hypercohone G （12）, betulinic acid （1 3）, oleanolic acid 3.13-caffeate （14）, and isoastilbin （1 5）. Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2-7 and 10-1 5 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron

Five new polycyclic polyprenylated acylphloroglucinols(1-5),ascyrones A-E,and four known compounds(6-9)were isolated from the aerial parts of Hypericum ascyron.All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group,belonged to type B bicyclic polyprenylated acylphloroglucinols(BPAPs).Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism(ECD)data.The anti-inflammatory,neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated.Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide(LPS)-induced RAW264.7 cells.Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells.Meanwhile,compound 1 showed mild neuroprotective activity against corticosterone(CORT)-induced PC 12 cell damage at 10 μmol-L^(-1).