Isolation and Characterization of Bioactive Cyclotides from Viola labridorica

Many Violaceae plants contain cyclotides, which are plant cyclopeptides distinguished by a cyclic cystine knot motif with 28–37 amino acid residues. In the current study, four new cyclotides, vila A–D ( 1 – 4 , resp.), together with a known cyclotide, varv D ( 5 ), were isolated from Viola labridorica (Violaceae). A chromatography‐based method was used to isolate the cyclotides, which were characterized using tandem mass spectrometry and 2D‐NMR spectroscopy. Several of the cyclotides showed cytotoxic activities against five cancer cell lines, i.e., U251, MDA‐MB‐231, A549, DU145, and BEL‐7402, with vila A and B ( 1 and 2 , resp.) being the most cytotoxic. The isolated cyclotides showed no antibacterial activity against Staphyloccocus aureus and Candida albicans. Homology modeling of the cyclotide structures was used to analyze structure–activity relationships.     

Eupatozansins A – C,Sesquiterpene Lactones from Eupatorium chinense var. tozanense

Phytochemical investigation of Eupatorium chinense var. tozanense has resulted in the isolation of three new germacranolides, designated as eupatozansins A–C ( 1 – 3 ), along with five known compounds, (5S,6R,7R,8R)‐8‐angeloyloxy‐2‐oxoguaia‐1(10),3,11(13)‐trien‐12,6‐olide ( 4 ), costunolide ( 5 ), leptocarpin ( 6 ), 2α‐hydroxyeupatolide 8‐O‐angelate ( 7 ), and quercetin ( 8 ). The structures of the new compounds were identified by 1D and 2D NMR experiments, as well as high‐resolution mass spectrometry. The in vitro cytotoxic activities of compounds 1 – 8 were evaluated.     

Dapholidins A – C,New Isomeric Biisoflavonoids From Daphne oleoides

Three new isomeric biisoflavonoids, dapholidins A–C ( 1 – 3 , resp.), have been isolated from the AcOEt‐soluble fraction of the MeOH‐soluble extract of the roots of Daphne oleoides, along with the known compounds daphwazirin ( 4 ), daphnetin 8‐O‐β‐D ‐glucopyranoside ( 5 ), daphnin ( 6 ), daphneticin 4″‐O‐β‐D ‐glucopyranoside ( 7 ), and 6,7‐dihydroxy‐3‐methoxy‐8‐[2‐oxo‐2H‐1‐benzopyran‐7‐(O‐β‐D ‐glucopyranosyl)‐8‐yl]‐2H‐1‐benzopyran‐2‐one ( 8 ). The structures of the new compounds were determined by spectroscopic analyses, including 1D‐ and 2D‐NMR.     

Itosides A – I,New Phenolic Glycosides from Itoa orientalis

Eight new benzoylated gentisyl alcohol (=2‐(hydroxymethyl)benzene‐1,4‐diol) glucosides, itosides A–H ( 1 – 8 ), together with the new pyrocatechol (=benzene‐1,2‐diol) glycoside itoside I ( 9 ) were isolated from the bark and twigs of Itoa orientalis (Flacourtiaceae). In itosides B–D ( 2 – 4 ), the gentisyl alcohol moiety was esterified by 1‐hydroxy‐6‐oxocyclohex‐2‐ene‐1‐carboxylic acid, while itosides E–H ( 5 – 8 ) contained instead an additional 2‐hydroxybenzoic acid moiety. The compounds were accompanied by the known derivatives 4‐hydroxytremulacin ( 10 ), poliothyrsoside ( 11 ), poliothyrsin ( 12 ), homaloside D ( 13 ), tremulacin, and pyrocatechol β‐D ‐glucopyranoside. The structures of the new compounds were elucidated by spectral and chemical methods.     

Three New Bisabolane Sesquiterpenes from Ligularia songarica

Three new bisabolane sesquiterpenes, songaricalarins F–H ( 1 – 3 , resp.), and five known analogs, 4 – 8 , were isolated from roots and rhizomes of Ligularia songarica. The structures were elucidated by spectroscopic methods, including 2D‐NMR techniques. The isolated compounds were also evaluated for their cytotoxic activities, against human lung carcinoma (A‐549) and human breast adenocarcinoma (MCF‐7) cell lines, and three compounds were found to show moderate cytotoxicities.     

Cytotoxic Naphtho‐γ‐pyrones from the Mangrove Endophytic Fungus Aspergillus tubingensis (GX1‐5E)

Four new dimeric naphtho‐γ‐pyrones, named rubasperone D ( 1 ), rubasperone E ( 2 ), rubasperone F ( 3 ), and its atropisomer rubasperone G ( 4 ), together with four known monomeric naphtho‐γ‐pyrones, TMC 256 A1 ( 5 ), rubrofusarin B ( 6 ), fonsecin ( 7 ), and flavasperone ( 8 ), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1‐5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D‐ and 2D‐NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF‐7, MDA‐MB‐435, Hep3B, Huh7, SNB19, and U87 MG with IC₅₀ values between 19.92 and 47.98 μM . Compounds 1, 6 , and 8 also showed mild cytotoxic activity.     

Irciformonins E – K,C22‐Trinorsesterterpenoids from the Sponge Ircinia formosana

Chemical investigation of the sponge Ircinia formosana resulted in the isolation of seven new linear C₂₂‐sesterterpenoids, irciformonins E–K ( 1 – 7 ) in addition to irciformonin A ( 8 ), a previously isolated furanosesterterpenoid (=a furan‐moiety‐containing sesterterpenoid) from the same species. The structures were determined by interpretation of HR‐ESI‐MS and 2D‐NMR spectra. The structure of irciformonin A ( 8 ) was revised. Compound 5 exhibited significant inhibition of peripheral blood mononuclear cell proliferation induced by phytohemaglutinin.     

Heteroclitins N – Q,New Compounds from Stems of Kadsura heteroclita (Roxb.) Craib

From the stems of Kadsura heteroclita (Roxb .) Craib , a new novel C₁₉ homolignan, heteroclitin N ( 1 ), as well as three new lignans, heteroclitins O? Q ( 2 – 4 ), were isolated. Their structures were elucidated based on spectral analysis, including 1D and 2D NMR experiments. There is an additional spirocyclic oxirane system in heteroclitin O ( 2 ), which is the first example of a lignan with an oxirane ring in a spirobenzofuranoid dibenzocyclooctene structure in the genus Kadsura.     

New Polyketides Isolated from Botryosphaeria australis Strain ZJ12‐1A

Four new polyketides, botryosphaerones A–D ( 1 – 4 , resp.), were obtained from the fermentation culture of Botryosphaeria australis strain ZJ12‐1A, together with four known compounds, O‐methylasparvenone ( 5 ), 6‐ethyl‐2,7‐dimethoxyjuglon ( 6 ) and its monoacetyl derivative 7 , and O‐methylaspmenone ( 8 ). Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR experiments, and HR‐Q‐TOF mass spectrometry, and by comparison with reported data. All compounds were evaluated for their cytotoxic and antimicrobial activities in vitro. Only compounds 6 and 7 showed cytotoxic and antimicrobial activities, as already reported.     

Tasumatrols P – T,Five New Taxoids from Taxus sumatrana

The phytochemical investigation of the more polar fractions from the leaves and twigs of Taxus sumatrana (Taxaceae) afforded five new taxane diterpene esters, tasumatrols P–T ( 1 – 5 ) possessing an 11(15→1),11(10→9)‐diabeotaxane skeleton. Compounds 1, 4 , and 5 contain an α‐hydroxy group at C(14), while 3 has no OH group at either C(13) or C(14). Compound 2 is a natural 4,5‐acetonide derivative, while 4 has an unusual spiro‐connected 2‐hydroxy‐2‐phenyl‐1,3‐dioxolane ring. Ten known taxoids, were also isolated in the course of the chromatographic fractionation. Five additional new O‐acetyl derivatives 3a, 4a, 4b, 5a , and 5b were prepared from the taxanes 3 – 5 . The structures of all new compounds were established on the basis of their spectroscopic analyses. Compound 1 showed mild cytotoxic activity against human Hela and Daoy tumor cells.     

Vinmajorines C – E,Monoterpenoid Indole Alkaloids from Vinca major

Three new monoterpenoid indole alkaloids, vinmajorines C–E ( 1 – 3 ), along with 18 known analogues ( 4 – 21 ), were isolated from the whole plants of Vinca major. The new structures were elucidated as (5α,15β,16R,17α,19β,20α,21β)‐10,17‐dimethoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐19‐ol ( 1 ), (5α,15β,16R,17α,20α,21β)‐10‐methoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐17‐ol ( 2 ), and (5α,15β,16R,17α,20α,21β)‐10‐methoxy‐21‐methyl‐18‐oxa‐5,16‐cycloyohimban‐17‐yl acetate ( 3 ), respectively, by extensive NMR and MS analysis and comparison with known compounds. Compounds 1 – 3 were evaluated for their cytotoxic activities against five human cancer cell lines, compounds 1 and 3 showing moderate cytotoxic activities.     

Five New C19‐Diterpenoid Alkaloids from Aconitum hemsleyanum

Five new C₁₉‐diterpenoid alkaloids, named hemsleyaconitines A–E ( 1 – 5 , resp.), were isolated from Aconitum hemsleyanum Pritz. By UV, IR, MS, 1D‐ and 2D‐NMR analyses, their structures were elucidated as 18‐dehydroxygeniculatine D ( 1 ), 6‐hydroxy‐14‐O‐veratroylneoline ( 2 ), 14‐O‐acetyl‐8‐ethoxysachaconitine ( 3 ), 18‐veratroylkaracoline ( 4 ) and 8‐O‐ethylaustroconitine B ( 5 ).     

Eremosides A – C,New Iridoid Glucosides from Eremostachys loasifolia

Eremosides A–C ( 1 – 3 ), three new iridoid glucosides, were isolated from the AcOEt‐soluble fraction of the EtOH extract of the whole plant of Eremostachys loasifolia, along with buddlejoside B ( 4 ), 10‐O‐benzoylcatalpol ( 5 ), and pakiside A ( 6 ) reported for the first time from this species. The structures of these compounds were elucidated by spectroscopic data including 2D‐NMR, FAB‐MS, ESI‐MS, as well as by acid and basic hydrolyses.     

Eight New Cucurbitane Glycosides,Kuguaglycosides A – H,from the Root of Momordica charantia L.

Eight new cucurbitane glycosides, kuguaglycosides A–H ( 1 – 8 , resp.), together with five known analogues, 3β,23‐dihydroxycucurbita‐5,24‐dien‐7β‐yl β‐D ‐glucopyranoside ( 9 ), karaviloside III ( 10 ), karaviloside V ( 11 ), karaviloside XI ( 12 ), and momordicoside K ( 13 ), were isolated from the root of Momordica charantia L. The structures of the new compounds were determined on the basis of spectroscopic and chemical methods.     

Bioactive Cytochalasins from Aspergillus flavipes,an Endophytic Fungus Associated with the Mangrove Plant Acanthus ilicifolius

Five new cytochalasins, Z₁₆–Z₂₀ ( 1 – 5 ), and three known ones, 6 – 8 , were isolated from Aspergillus flavipes, an endophytic fungus associated with Acanthus ilicifolius. Their structures were elucidated on the basis of comprehensive spectral analysis. Cytochalasin Z₁₇ ( 2 ) and rosellichalasin ( 8 ) showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 5.6 and 7.9 μM , respectively.     

Four New Nortriterpenoids from Schisandra lancifolia

Four new highly oxygenated nortriterpenoids, lancifodilactones O–R ( 1 – 4 ), together with six known ones, i.e., 5 – 10 , were isolated from the leaves and stems of Schisandra lancifolia. Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR experiments and mass spectrometry. Compounds 1 – 3 were evaluated for their cytotoxicity against NB4, A549, SHSY5Y, PC‐3, and MCF‐7 cell lines. No compounds exhibited significant cytotoxicity, the IC₅₀ values being above 50 μM .     

Artabotryols A – E,New Lanostane Triterpenes from the Seeds of Artabotrys odoratissimus

Six new lanostane triterpenes, artabotryols A, B, C1, C2, D, and E ( 1, 2, 3a, 3b, 4 , and 5 , resp.) have been isolated from the seeds of Artabotrys odoratissimus (Annonaceae). Their structures have been established as (3α,22S,25R)‐3‐hydroxy‐22,26‐epoxylanost‐8‐en‐26‐one ( 1 ), (3α,22S,25R)‐22,26‐epoxylanost‐8‐ene‐3,26‐diol ( 2 ), (3α,22S,25R,26R)‐26‐methoxy‐22,26‐epoxylanost‐8‐en‐3‐ol ( 3a ), (3α,22S,25R, 26S)‐26‐methoxy‐22,26‐epoxylanost‐8‐en‐3‐ol ( 3b ), (3α,22S,25R)‐3,22‐dihydroxylanost‐8‐en‐26‐oic acid ( 4 ) and (3α,7α,11α,22S,25R)‐3,7,11‐trihydroxy‐22,26‐epoxylanost‐8‐en‐26‐one ( 5 ) by spectroscopic studies and chemical correlations.     

Triterpene Saponins from Entada phaseoloides

Four oleanane‐type triterpene saponins, phaseoloideside A–D ( 1 – 4 ), were isolated from the seed kernels of Entada phaseoloides, along with rheediinoside B. The structures of the four new compounds were established by 2D‐NMR spectroscopic methods, HR‐ESI‐MS analysis, and chemical degradation. Phaseoloideside D ( 4 ) showed cytotoxic activity against the Eca‐109 cell line with an IC₅₀ value of 28.0 μM .     

Baimantuoluolines D – F,Three New Withanolides from the Flower of Datura metel L.

Three new withanolide compounds, named baimantuoluolines D–F, along with three known withanolides and a lignan were isolated from the flower of Datura metel L., the parts effective against psoriasis. The structures of the new compounds were elucidated as (5α,6β,12β,20R,22R,24R,25S)‐21,24‐epoxy‐5,6,12‐trihydroxy‐27‐methoxy‐1‐oxowith‐2‐enolide ( 1 ), (5α,6β,12β,20R,22R,24R,25S)‐21,24‐epoxy‐5,6,12,27‐tetrahydroxy‐1‐oxowith‐2‐enolide ( 2 ), and (5α,6β,12β,22R)‐5,6,12,21‐tetrahydroxy‐1‐oxowith‐24‐enolide( 3 ) on the basis of physicochemical evidence.     

Four New Pregnane Steroids from Aglaia abbreviata and Their Cytotoxic Activities

Four new pregnane steroids, aglaiasterols A–D ( 1 – 4 ), have been isolated from the EtOH extract of stems of Aglaia abbreviata. They were identified as (3α,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 1 ), (3β,5α,17E)‐3‐hydroxypregn‐17‐en‐16‐one ( 2 ), (3β,5α,17Z)‐3‐hydroxypregn‐17‐en‐16‐one ( 3 ), and (3α,5α,20S*)‐3‐hydroxy‐16‐oxopregnan‐20‐yl acetate ( 4 ) on the basis of spectroscopic methods, including 1D‐ and 2D‐NMR techniques. Compounds 1 – 4 were evaluated for their cytotoxic activities against K562 (human leukemia), MCF‐7 (human breast cancer), and KB (human oral epithelium cancer) cells, and drug‐resistant cells of K562/A02, MCF‐7/ADM, and KB/VCR. These isolates showed weak to moderate inhibitory effects on the growth of the tested cell lines.