Six new dammarane-type triterpene saponins from the processed leaves of Panax notoginseng

Six new dammarane-type triterpenoid saponins, notoginsenosides SFt₅–SFt₁₀ (1–6) were isolated from the processed leaves of Panax notoginseng (Burk.) F.H.Chen (Araliaceae), together with eight known notoginsenosides (7–14), fourteen known ginsenosides (15−28), two known vinaginsenosides (29−30), and one known gypenoside (31). Their structures were established by detailed spectroscopic analysis (NMR, UV, IR, HRESI-MS) and acidic hydrolysis. Four compounds notoginsenoside SFt₁ (7), ginsenosides Rg₅ (17), C-Mc (23) and 20(R)–Rg₃ (25) have significant protective effects against L-glutamate-induced SH–SY5Y nerve injury (10 μM).     

Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle)

Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1–7) inhibited both monophenolase (IC₅₀ = 1.7–7.6 µM) and diphenolase (IC₅₀ = 12.1–44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8–10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of E_met·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with K_SV values of 0.06–0.27 × 10⁴ L·mol⁻¹, which are well correlated with IC₅₀s. In kinetic study, all flavonolignan (1–7) were mixed type I (K_I < K_IS) inhibitors, whereas their mother skeletons (8–10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.     

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC₅₀ value of 15.41?μM.     

Unusual C19-diterpenoid alkaloids from Aconitum vilmorinianum var. patentipilum

Three new C₁₉-diterpenoid alkaloids vilmotenitines A-C (1-3), together with seven known ones, vilmorine D (4), talatizidine (5), isotalatizidine (6), vilmorrianine B (7), vilmorrianine D (8), talatizamine (9), 8-deacetyl-yunaconitine (10), were isolated from Aconitum vilmorinianum var. patentipilum. Vilmotenitines A (1) and B (2) are the second natural occurrences of C₁₉-diterpenoid alkaloids with a unique rearranged six-membered B ring formed by the C₍₈₎–C₍₁₀₎ linkage.     

Cytotoxic triterpenes with diverse skeletons from Amoora tsangii

Two new 29-nor-cycloartane triterpenes, amooratsanols A and B (1, 2) along with nine known compounds including two 29-nor-cycloartane triterpenes (3, 9), two lupane triterpenes (4, 5), two cycloartane triterpenes (6, 10), two dammarane triterpenes (7, 8), as well as one dinorcycloartane triterpene (11) were isolated from the leaves and twigs of Amoora tsangii (Merr.) X. M. Their structures were established by spectroscopic methods (IR, HRESIMS, and NMR). The cytotoxicity of 1–11 was evaluated against the human fibro sarcoma HT1080, esophageal cancer TE, and non-small cell lung cancer A549 cell lines by the CCK8 assay. Cycloartanes (1–3, 6, and 9–11) displayed significant cytotoxic activity with IC₅₀ values ranging from 2.56 to 19.05 μM. Among these triterpenes, mooratsanol A (1) showed the most potent cytotoxic activity, with IC₅₀ values ranging from 2.56 to 5.10 μM.     

Three new C19-diterpenoid alkaloids from Delphinium tianshanicum W. T. Wang

Three new C₁₉-diterpenoid alkaloids, tianshanisine (1), tianshanine (2) and tianshanidine (3), together with six known C₁₉-diterpenoid alkaloids (4–9) were isolated from the whole herb of Delphinium tianshanicum W. T. Wang. Their structures were established on the basis of spectroscopic analyses, including HR-ESI-MS and 1D and 2D NMR.     

Dibrefeldins A and B,A pair of epimers representing the first brefeldin A dimers with cytotoxic activities from Penicillium janthinellum

Dibrefeldins A and B (1 and 2), two unexpected brefeldin A (BFA) dimers, as well as brefeldin F (3), brefeldin G (4), and 14-hydroxy-BFA (5), three new BFA derivatives, together with three new naturally occurring BFA derivatives (6–8) and four known analogues (9–12), were isolated from the fungus Penicillium janthinellum. Dibrefeldins A and B (1 and 2) represent the first examples of BFA dimers formed by an esterification between two BFA monomer units. Brefeldin F (3) has an α,β-unsaturated γ-lactone ring, and this moiety was first discovered in naturally occurring BFA derivatives. The structures and relative/absolute configurations of these derivatives were elucidated by extensive spectroscopic methods, ¹³C NMR calculations, and single-crystal X-ray diffraction. Compounds 1, 2, 8, and 9 showed excellent cytotoxic activities against six cancer cell lines with IC₅₀ values ranging from 0.01 to 4.45 μM.     

Chemical constituents from Cynanchum paniculatum (Bunge) Kitag

Twenty-nine compounds, including five acetophenone derivatives (1–5), three phenanthroindolizidine alkaloids (12–14), seven pentacyclic triterpenoids (15–21) and five C₂₁ steroidal sapogenins (22–26), were isolated from the root of Cynanchum paniculatum (Bunge) Kitag. Their structures were determined by spectroscopic methods and comparison with reported data. Moreover, the chemotaxonomic relationships were also discussed. As a result, acetophenone derivatives, pentacyclic triterpenoids and C₂₁ pregnane sapogenins can be recognized as chemotaxonomic markers for Cynanchum genus, and C. paniculatum has close relationships with some species of genus Cynanchum.     

Daphnodorin dimers from Edgeworthia chrysantha with α-glucosidase inhibitory activity

Four daphnodorin dimers named herein as edgechrins A–D (1–4) were isolated from the stems and twigs of Edgeworthia chrysantha Lindl. along with four known compounds identified as daphnodorin A (5), B (6), C (7) and I (8). Their structures were established by spectroscopic methods, including IR, HR-MS, and 1D- and 2D NMR. All of these compounds showed potent in vitro α-glucosidase inhibitory activity with IC₅₀ values in the range of 0.4–20 μM.     

New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity

Bioassay-guided fractionation of the marine-derived endophytic fungus Paecilomyces variotii resulted in the isolation of two new butenolides, namely, butyrolactone IX (1) and aspulvinone O (7), together with eight known related congeners, butyrolactones I, IV, V, and VI (2–5), aspernolide A (6), and aspulvinones H, C, and D (8–10). Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. All of the isolated butenolides were tested for their activity against DPPH radicals and the results showed that butyrolactones (1–6) possessed potent activity with IC₅₀ values ranging from 38.0 to 186.3 μM, while aspulvinones (7–10) exhibited significant activities with IC₅₀ values ranging from 11.6 to 29.4 μM, which are stronger than that of the positive control BHT (with IC₅₀ 117.7 μM). The preliminary structure–activity relationship was discussed.     

Neolignans and phenylpropanoids from the roots of Piper taiwanense and their antiplatelet and antitubercular activities

Bioassay-guided fractionation of roots from Piper taiwanense led to isolation of three neolignans, diallylcatechol (1) and neotaiwanensols A, B (2, 3), two diphenylpropanoid ethers, taiwandimerols A, B (4, 5), with one phenylpropanoid, 2,3-diacetoxy-1-methoxy-5-allylbenzene (6), previously unknown in nature, together with 18 known compounds (7–24). Their structures were elucidated by spectroscopic evidence. Among the isolates, hydroxychavicol acetate (7), and 4-allylcatechol (8) showed potent inhibitory activities against platelet aggregation induced by collagen, with IC₅₀ values of 2.1, and 5.3 μM, respectively. Hydroxychavicol acetate (7), 4-allylcatechol (8), and trans-caffeicaldehyde (9) showed antitubercular activities against Mycobacterium tuberculosis H₃₇Rv, with MIC values of 30.3, 27.6, and 25.5 μg/mL, respectively.     

Diterpenoids from the stems of Tripterygium hypoglaucum (Celastraceae) and cytotoxic evaluation

Four new diterpenoids, 2α,16α-hydroxy-ent-kauran-19,20-olide (1), isopimara-8(14),15-diene-11β,19-diol (2), isopimara-8(14),15-diene-12α,19-diol (3), and 3-oxo-14,15-dihydroxyabieta-8,11,13-trien-19-ol (4), along with seven known compounds (5–11) were isolated from Tripterygium hypoglaucum. Their structures were established on the basis of extensive spectroscopic analysis. Triptolide (5) and 2-epitripdiolide (6) showed significant cytotoxicity against A549, DU145, KB, KBvin and MDA-MB-231 cell lines with IC₅₀ values of 0.0012–0.1306 μM in vitro.     

Bioactive secondary metabolites from the marine-associated fungus Aspergillus terreus

Three new compounds, including a prenylated tryptophan derivative, luteoride E (1), a butenolide derivative, versicolactone G (2), and a linear aliphatic alcohol, (3E,7E)-4,8-dimethyl-undecane-3,7-diene-1,11-diol (3), together with nine known compounds (4–12), were isolated and identified from a coral-associated fungus Aspergillus terreus. Their structures were elucidated by HRESIMS, one- and two-dimensional NMR analysis, and the absolute configuration of 2 was determined by comparison of its electronic circular dichroism (ECD) spectrum with the literature. Structurally, compound 1 featured an unusual (E)-oxime group, which occurred rarely in natural products. Compounds 1–3 were evaluated for the α-glucosidase inhibitory activity, and compound 2 showed potent inhibitory potency with IC₅₀ value of 104.8 ± 9.5 μM, which was lower than the positive control acarbose (IC₅₀ = 154.7 ± 8.1 µM). Additionally, all the isolated compounds were evaluated for the anti-inflammatory activity against NO production, and compounds 1–3, 5–7, and 10 showed significant inhibitory potency with IC₅₀ values ranging from 5.48 to 29.34 μM.     

Alkaloids from the mangrove endophytic fungus Diaporthe phaseolorum SKS019

Six new alkaloids including four new chromeno[3,2-c]pyridines, diaporphasines A-D (1–4), and two new isoindolinones, meyeroguillines C and D (6–7), as well as three known compounds meyeroguilline A (5), 5-deoxybostrycoidin (8), and fusaristatin A (9), were isolated from an endophytic fungus Diaporthe phaseolorum SKS019. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Compounds 1–9 are alkaloid components reported for the first time from the Diaporthe sp., and diaporphasines A-D (1–4) are the third examples of alkaloids possessing the unique chromeno[3,2-c]pyridine nucleus. All isolated compounds 1–9 were evaluated for their cytotoxic activity in vitro using MDA-MB-435, HepG2, MCF10A, HCT116, and NCI-H460 human cell lines. Compound 8 exhibited cytotoxicity against MDA-MB-435 and NCI-H460 human cancer cell lines with IC₅₀ values of 5.32 and 6.57 μM, respectively, and compound 9 showed growth-inhibitory activity against MDA-MB-435 human cancer cell line with IC₅₀ value of 8.15 μM.     

New sesquiterpene lactone glucosides from the roots of Ferula varia

Five new eudesmane- (1–5), two new guaiane- (6 and 7) and one new germacrane-type (8) sesquiterpene lactone glucosides were isolated from the H₂O-soluble fraction of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configuration of 1 was determined by modified Mosher's method.     

Three new glycosides from the whole plant of Clematis lasiandra Maxim and their cytotoxicity

Phytochemical investigation on the whole plant of Clematis lasiandra Maxim led to the isolation of two new phenolic glycosides (1 and 2), one new lignanoid glycoside (3), together with three known lignanoid glycosides (4–6). The structures of the new compounds were elucidated as 4-O-β-d-galactopyranosyl-ethyl-E-caffeate (1), 4-O-β-d-galactopyranosyl-3-hydroxyl-phenylethene (2) and (8R)-3,3′-dimethoxy-4,4′,9,9′-tetrahydroxy-5′,8-lignan 3′-O-β-d-glucopyranoside (3), on the basis of extensive spectral analysis and chemical evidence. The characteristic of the polymerized C-5′–C-8 type lignanoid aglycone in glycoside 3 was found from genus Clematis for the first time. Compounds 1–6 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901, the new glycosides 1 and 2 showed significant cytotoxicity against those three tumor cell lines with IC₅₀ in the range from 9.73 to 22.31 μM, while lignanoid glycosides 3–6 showed weak cytotoxicity to those test cell lines with IC₅₀ value more than 52.71 μM.     

Phytochemical and chemotaxonomic study of Pulsatilla cernua (Thunb.) Bercht. ex J. Presl

Twenty-two compounds were isolated from the 70% EtOH–H₂O extract of Pulsatilla cernua (Thunb.) Bercht. ex J. Presl roots, and their structures were determined based on ¹H NMR, ¹³C NMR and MS spectroscopic data, including (+)-pinoresinol (1), matairesinol (2), 4-ethoxycinnamic acid (3), p-hydroxy ethyl cinnamate (4), 3-(4′-methoxyphenyl)-2(E)-propenoic acid (5), methyl 4-hydroxycinnamate (6), radicol (7), cryptomeridiol (8), fraxinellone (9), diolmycin B2 (10), hederagonic acid (11), hederagenin (12), oleanolic acid (13), 3-O-α-L-arabinopyranosyl-oleanolic acid (14), hederagenin 3-O-α-L-arabinopyranoside (15), 3-O-[α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] oleanolic acid (16), hederasaponin B (17), kizutasaponin K₁₂ (18), patrinia saponin H3 (19), hederacholichiside F (20), cernuoside A (21) and cernuoside B (22). Eight compounds (3–10) were isolated and identified from the genus Pulsatilla for the first time.     

Supercritical fluid extraction assisted isolation of sesquiterpene lactones with antiproliferative effects from Centipeda minima

Pseudoguaianolide sesquiterpene lactones minimolides A (1), B (2), C (3) and D (4) and two guaianolide sesquiterpene lactones minimolides E (5) and F (6), along with seven known ones (7–13), were isolated from the supercritical fluid extract of Centipeda minima. The structures of these compounds were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D-NMR and 2D-NMR), and the complete structure and stereochemistry of 1 was further confirmed by X-ray diffraction analysis. Compounds 1, 5–8, 11 and 13 displayed inhibitory activity against human nasopharyngeal cancer cells (CNE) with IC₅₀ values ranging from 1.1 to 20.3 μM. Compound 13 containing both α-methylene-γ-lactone and α, β-unsaturated cyclopentenone moieties exhibited even stronger inhibitory activity than that of cisplatin (positive control) through cell cycle arrest at G2/M phase. Isolation of six sesquiterpene lactones from Centipeda minima highlighted the potential of supercritical fluid extraction for enrichment of minor constituents for phytochemical study.     

Nitric oxide inhibitory constituents from Siegesbeckia pubescens

Two new sesquiterpenoids (1 and 2) and a new ent-pimarane type diterpenoid (3), together with eighteen known compounds (4–21), were isolated from the whole plants of Siegesbeckia pubescens. The structures of the new compounds were determined on the basis of 1D-, 2D NMR and HRESIMS data. All compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Of these, highly oxygenated germacrane type sesquiterpenoids (1–2 and 13–14) showed significant inhibitory effects with IC₅₀ values ranging from 3.9 to 16.8 μM.     

Guanacastane-type diterpenoids from Coprinus radians

Thirteen diterpenoids, named radianspenes A–M (1–13), including three lactams radianspenes J (10), K (11) and L (12) and one dimer radianspene M (13), were isolated from fermentation products of the higher fungal strain Coprinus radians M65. All these compounds possessing guanacastane skeleton were evaluated for antitumor activity using MDA-MB-435 cell line. Radianspene C exhibited inhibitory activity with IC₅₀ of 0.91 μM.