neo-Clerodane diterpenoids from Salvia dugesii and their bioactive studies

Salvia dugesii is an invasive plant in Yunnan,China.To tentatively explore its utilization,a systematic phytochemical investigation was carried out on this plant,which led to the isolation of five new neo-clerodane diterpenoids,dugesins C-G(1-5),together with six known ones.Their structures were determined by comprehensive NMR and MS spectroscopic analysis.It was noteworthy that the eleven isolates,composed of five different carbocyclic systems derived from the neo-clerodane diterpenoid skeleton,were reported from the same plant for the first time.The anti-feedantial,cytotoxic,and antiviral activities of the isolates were evaluated.Dugesin F(4)was tested to be a non-toxic antiviral compound against influenza virus FM1.

Two New neo-Clerodane Diterpenoids from Scutellaria barbata

Two new neo-clerodane diterpenoids, 6,7-dibenzoyloxybarbatin C （1, named barbatin D） and 6-（2-acetoxy-3-methylbutanoloxy）-7-（2-carbonyl-3-methylbutanoyloxy） barbatin C （2, named barbatin E） were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic methods including extensive 1 D and 2D NMR analyses. In vitro, compounds 1-2 showed cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, and with IC50 values in the range of 3.5-6.7μM.

TEUPONXN: A NEO-CLERODANE DITERPENE FROM TEUCRIUM JAPONICUM

A nco—clcrodane diterpcne, teuponin, was isolated from the aerial parts of Teucrium japonicum. Its structure was established as (12S)—19—nor—neo—clcroda— 15a—hydroxy—4,13-diene— 16,15;18,6β;20,12-triolide by spcctroscopic means. The absolute configuration was determined by X—ray diffraction analysis and CD spectrum.

TEUPERNIN D: A CHLORINE-CONTAINING NEO-CLERODANE DITERPENE FROM TEUCRIUM PERNYI

A new chlorine-containing neo-clerodane diterpene, teupernin D, was isolated from the aerial parts of Teucrium pernyi. The structure for teupernin D was established as (12S) -15, 16-epoxy-8β-hydroxy-17-chloro-19-nor10α-neo-cleroda-4, 13(16), 14-triene-18,6β;20,12-diolide on the basis of spectral evidence. The absolute configuration was established by CD spectrum and confirmed by X-ray crystallographic analysis.

Insight of Natural Compounds Halimane Diterpenoids against Mycobacterium tuberculosis: Virtual Screening, DFT, Drug-Likeness, and Molecular Dynamics Approach

In the purpose to design novel antituberculosis (anti-TB) drugs agents against Mycobacterium tuberculosis (Mtb), we have built a molecular library around 42 Halimane Diterpenoids isolated from natural sources. Two Mtb enzymes drug targets (Mtb Mycothiol S-transferase and Mtb Homoserine transacetylase) have been adopted. The pharmacological potential was investigated through molecular docking, molecular dynamics simulation, density functional theory (gas phase and water) and ADMET analysis. Our results indicate that (2R,5R,6S)-1,2,3,4,5,6,7,8-octahydro-5-((E)-5-hydroxy-3-methylpent-3-enyl)-1,1,5,6-tetramethylnaphtha-lene-2-ol (compound 20) has displays higher docking score with each of the selected drug targets. In addition, this molecule exhibits a satisfactory drug potential activity and a good chemical reactivity. Its improved kinetic stability in the Mtb Mycothiol S-transferase enzyme reflects its suitability as a novel inhibitor of Mtb growth. This molecule has displayed a good absorption potential. Our results also show that its passive passage of the intestinal permeability barrier is more effective than that of first-line treatments (ethambutol, isoniazid). In the same way, this anti-TB druglikeness has shown to be able to cross the blood brain barrier.

A New Diterpenoid from Aralia fargesii

Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), the structure of compound 1 was established to be 17-acetoxy-16alpha-ent-kauran-19-oic acid The other three known compounds were identified as ent-pimera-8(14) 15-dien-19-oic acid (2), 16alpha-hydroxy-( -)-kauran-19-oic acid (3) and 16alpha-17-dihydroxy-ent-kauran-19-oic acid (4). The three known diterpenoids were obtained from this plant for the first time.

Diterpenoids from the Roots of Agastache rugosa

Agastol (2), a new diterpene, was isolated from the roots of Agastache rugosa together with its isomer, named isoagastol (3) Their structures were established on the basis of spectral methods The structures of agastol (2) and isoagastol (3) was elucidated as 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 4(18),8,11,13 tetraen 7 one and 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 3,8,11,13 tetraen 7 one Isoagastol was isolated for the first time from natural sources

Antioxidant,lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides

Objective:To investigate the antioxidant enicacy of a biologically active dilerpenoid compound sugiol isolated from Metasequoia glyptostroboides(M.glyptostroboides)in various antioxidant models.Methods:An abietane type diterpenoid sugiol,isolated from ethyl acetate extract of M.glyptostroboides cones,was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl radicals.Results:The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities.Consequently,the sugiol exerted lipid peroxidation inhibitory effect by 76.3%as compared to a-tocopherol(80.13%)and butylaled hydroxyanisole(76.59%).In addition,the sugiol had significant scavenging activities of l,l-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%,72.42%,72.99%and 85.04%,when compared to the standard compound ascorbic acid(81.69%,74.62%,73.00%and 73.79%)and a-tocopherol/butylated hydroxyanisole(84.09%,78.61%,74.45%and 70.02%),respectively.Conclusions:These findings justify the biological and traditional uses of M.glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.

Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways

AIM:To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori(H.pylori)-infected inflammation,intestinal metaplasia,and nuclear factor kappa B(NF-κB)signaling pathway in vitro.METHODS:We used I-type H.pylori to infect human gastric epithelial gastric epithelium cell line(GES-1)cell lines,and then H.pylori-infected GES-1 cells were treated with radix curcumae(RC)-derived diterpenoid C of different concentrations(5,10,20μg/mL)and amoxicillin.The expression of p65,IκB kinase(IKK)αand IKKγproteins was detected with Western blotting,and the expression of interleukin(IL)-8,IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method.Data were analyzed using SPSS software ver18.0.For comparisons between groups of more than two unpaired values,one-way analysis of variance(ANOVA)was used.If an ANOVA F value was significant,post hoc comparisons were performed between groups.If results were not normally distributed,the Mann-Whitney U test was used to compare two groups of unpaired values,whereas for comparisons between groups of more than two unpaired values,the Kruskal-Wallis H test was used.Statistical significance was established at P<0.05.RESULTS:The MTT assay results revealed the inhibited rate of GES-1,and indicated that the IC5 of RCderived diterpenoid C and amoxicillin all were 5μg/mL for gastric GES-1 cells.The expression of IL-8 was significantly increased,especially at 12 h time point;and the expression of IL-4 was decreased in H.pyloriinfected GES-1 cells.After H.pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin,the expression of IL-8was decreased at 12,24,48,72 h points(P<0.01),especially in high-concentration diterpenoid C(20μg/mL)group;and the expression of IL-4 was increased,especially in moderate and high-concentration diterpenoid C(10 and 20μg/mL)groups.RC-derived diterpenoid C had the inhibitory effects on H.pylori-induced p65 translocation from cytoplasm into cell nucleus,H.pylori-stimulant IkBαdegradation,the phosphorylation of p65 and IkBα,and the expression of IKKαand IKKβproteins.CONCLUSION:RC-derived diterpenoid C can block NF-κB signal pathway,effectively reducing the secretion of H.pylori-induced proinflammatory cytokine and increasing the secretion of anti-inflammatory cytokine.

New diterpenoid glucosides from Siegesbeckia pubescens

Five new diterpenoids isolated from Siegesbeckia pubescens, pubesides A similar toE, were established as ent-2 alpha ,15,16-trihydroxypimar-8(14)-en-2-O-beta -D-glucopyranoside (1), ent-15,16,19-trihydroxypimar-8(14)-en-19-O-beta -D-glucopyranoside (2), beta -D-glucopyranosyl-ent-15,16-dihydroxypimar-8(14)-en-19-oiclate (3), ent-2-oxo-15,16,19-trihydroxypimar-8(14)-en-19-O-beta -D-gluco-pyranoside (4), ent-2-oxo-15,16,19-trihydroxypimar-8(14)-en-19-O-beta -D-glucopyranoside-15,16-acetonide (5) by 1D and 2D NMR techniques.

New Diterpenoids from Coleus forskohlii

Two new diterpenoids, forskolin G and H were isolated from the chloroform extract of the roots of Coleus forskohlii, and based on spectroscopic data, their structures were identified as 1a-hydroxy-6b,7b-diacetoxy-8,13-epoxylabd-14-ene-11-one (1), and 1a,6b-diacetoxy-8,13-epoxy labd-14-ene-11-one (2), respectively.

The Diterpenoid Quinones from Coleus forskohlii

Two new diterpenoid quinones, colean S and T were isolated from the chloroform extract of the leaves of Coleus forskohlii, and based on spectroscopic data, their structures were identified as 1,4-phananthrenedione-4b,5,6,8a,9,10-hexahydro-3,9 beta ,10 alpha- tri-hydroxy-4b,7,8-trimethyl-2-propylene(2), respectively.

Kansuinine J,a new macrocyclic diterpenoid from the roots of Euphorbia kansui

A new macrocyclic diterpenoid,named kansuinine J（1）,was isolated from the roots of Euphorbia kansui.Its structure was characterized on the basis of spectroscopic analysis.

A new cassane diterpenoid lactone from the seed of Caesalpinia minax

A new cassane diterpenoid lactone was isolated from the seed of Caesalpinia minax. On the basis of spectral evidences, its structure was established as 12α-methoxyl, 5α, 14β-dihydroxy-1α, 6α, 7β-triacetoxycass-13（15）-en-16, 12-olide.

Two new ent-kaurane diterpenoids from Isodon excisoides

Two new ent-kaurane diterpenoids taihangexcisoidesin A and B （1 and 2）, were isolated from the EtOAc extract of the leaves of lsodon excisoides. Their structures were determined on the basis of spectroscopic methods.

New Diterpenoid Alkaloids from the Roots of Aconitum excelsum Reichb

Two new diterpenoid alkaloids have been isolated from roots of Aconitum excelsum Reichb. These new compounds were named excecoitine I and exceconidine II. The two structures were elucidated by spectroscopic methods as well as comparison with known compounds.

New Diterpenoid Alkaloids from Spiraea fritschiana var. parvifolia

Two new C20 hetisine-type diterpenoid alkaloids, spirafine III (1) and spirafine II (2), were isolated from the roots of Spiraea fritschiana var, parvifolia. Their structures were elucidated based on HRMS: IR and NMR spectral data, and chemical reaction.

A new ent-labdane diterpenoid lactone from Andrographis paniculata

A new ent-labdane diterpenoid lactone was isolated from Andrographis paniculata.Its structure was identified on the basis of spectral data including 2D NMR.

A new ent-kaurane diterpenoid from Isodon japonica

One new ent-kaurane diterpenoid,named maoyecrystal L was isolated from the EtOAc extract of the dried leaves of lsodon japonica.Its structure was established by various spectroscopic means and confirmed by X-ray crystallographic analysis.

Two new diterpenoids from Isodon serra

From the aerial part of Isodon serra, two new ent-6,7-seco-kaurane-type diterpenoids, 15α,20β-dihydroxy-6β- methoxy-6,7- seco-6,20-epoxy-1,7-olide-ent-kaur-16-ene （1） and 6α,15α-dihydroxy-20-aldehyde-6,7-seco-6,11α-epoxy-1,7-olide-ent-kaur-16- ene （2） were isolated. Their structures were elucidated by spectroscopic means.