Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation,structure elucidation and structure–activity relationship studies

Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1–6) along with fifteen known compounds (7–21). Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature. Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines. Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC₅₀ value of 0.3 μg/mL and 1.80 μg/mL, respectively.     

New cytotoxic compounds from flowers of Lawsonia inermis L.

Three new compounds, a bicoumarin A (1), a biflavonoid A (2), and a biquinone A (3), as well as 12 other known compounds, were isolated from the flower of Lawsonia inermis L. The structures were elucidated by spectral analysis and new compounds 2 and 3 then were further confirmed by ECD calculations and single-crystal X-ray diffraction crystallography respectively. The cytotoxicity of the compounds against four cancer cell lines, including MCF-7, Hela, HCT-116, and HT-29 were evaluated using MTT assay. The IC₅₀ values of compounds 3 and 5 against MCF-7, Hela, HCT-116, and HT-29 were 2.24, 1.42, 24.29, and 7.02 μM and 6.1, 2.44, 5.58, and 10.21 μM respectively. The two compounds exhibited stronger inhibitory activities than the positive control 5-fluorouracil (IC₅₀ = 7.34, 11.50, 36.17, 18.83 μM) against the four tested cell lines. These results demonstrated that compounds from the flowers of L. inermis L. showed cytotoxic activity on MCF-7, Hela, HCT-116, and HT-29 cell lines.     

Three new ursane-type triterpenes from the leaves of Rehmannia glutinosa

Three new ursane-type triterpenes, glutinosalactone A–C (1–3), were isolated from the 50% aqueous acetone extract of the leaves of Rehmannia glutinosa. Their structures were elucidated on the basis of spectral analysis (IR, NMR and MS spectroscopy). The cytotoxic effects of compounds 1–3 against three human cancer cell lines (MCF-7, MG63 and HepG2) were also evaluated. Compound 3 showed cytotoxic activities with IC₅₀ values of 8.35–39.25 μM.     

Two new sesquiterpenes from Artemisia sieversiana

Two new sesquiterpenes, together with 32 known compounds(3–34), were isolated from Artemisia sieversiana Ehrhart ex willd. and the compounds 3–21 were isolated from this plant for the first time. The new compounds were elucidated as 2α,9α-dihydroxymuurol-3(4)-en-12-oic acid (1) and 13α-methyl-(5αH,6αH,7αH,8αH)-austricin 8-O-β-D-glucopyranoside (2), respectively. The structural identification of these compounds was mainly achieved by spectroscopic methods including 1D and 2D NMR techniques, and the structure of compound 1 was confirmed by a single crystal X-ray diffraction experiment. Compounds 1–2 were evaluated for cytotoxic activity in vitro against MCF-7, NCI-H460 and Hep-G2 cell lines, respectively.     

Chemical constituents of Lobelia chinensis

Three new 2, 6-disubstituted piperidine alkaloids (1–3), one new polyacetylene (8), together with eight known compounds (4–7, 9–12) were isolated from the whole plants of Lobelia chinensis. Their structures were elucidated on the basis of spectroscopic data interpretation. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tube. Cytotoxicities of compounds 1–12 were tested against two human lung cancer cell lines, NCI-H292 and MSTO-211H. Compounds 8 and 9 exhibited moderate cytotoxic activity against the two cancer cell lines with the IC₅₀ values in the range of 9.31–12.36 μM.     

Sesquiterpene coumarin and sesquiterpene chromone derivatives from Ferula ferulaeoides (Steud.) Korov.

Five novel compounds — three sesquiterpene coumarin derivatives, ferulin A (1), B (2), and C (3), and two sesquiterpene chromone derivatives, ferulin D (4) and E (5), together with eleven known compounds (6–16) have been isolated from the roots of Ferula ferulaeoides (Steud.) Korov. Their structures were established by comprehensive spectroscopic analysis. The biosynthetic pathways leading to these compounds were proposed. The cytotoxicity of all these isolates against HepG2, MCF-7, and C6 cancer cell lines was evaluated and compound 7 displayed the highest potency against HepG2, MCF-7, and C6 with IC₅₀ values 39.9 μM, 37.7 μM, and 16.0 μM, respectively.     

Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity

Phytochemical investigation of ethanolic extract from the fruits of Schisandra chinensis led to the isolation of four new sesquiterpenes (1–4); their structures were determined by a combination of NMR (1D and 2D) and MS spectroscopic techniques. In addition, all these isolates were screened for their cytotoxic activities against MCF-7, Caco-2, Hela, Lncap, Hep G2 and MDA-MB231 cancer cell lines. Results indicated that compounds 2 and 3 displayed potent cytotoxic activity against Caco2 cell lines with IC₅₀ values of 17.10 μg/mM and 16.46 μg/mM, respectively.     

Diterpenoids from Isodon sculponeatus

Phytochemical investigation of the aerial parts of Isodon sculponeatus afforded six new 7,20-epoxy-ent-kauranoids, sculponins U–Z (1–6), and 11 known diterpenoids (7–17). The structures of these new compounds were elucidated primarily by means of extensive spectroscopic analysis, and the absolute configuration of 1 was determined by single crystal X-ray diffraction. Compound 5 exhibited weak cytotoxic activity against HL-60, SMMC-7721, MCF-7, and SW-480 cell lines, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC₅₀ value of 13.8 μM.     

Isocoumarins from American cockroach (Periplaneta americana) and their cytotoxic activities

Four new isocoumarins (1–4), along with three known ones (5–7), were isolated from the 70% ethanol extract of the whole body of the traditional Chinese insect medicine, American cockroach (Periplaneta americana). The structures with absolute configurations of new compounds were elucidated by extensive spectroscopic methods in combination with X-ray diffraction experiment and CD analyses. Compounds 3–5 showed significant cytotoxic activities in HepG2 and MCF-7 cells with IC₅₀ values in the ranges 6.41–23.91 μM and 6.67–39.07 μM, respectively.     

Carapanolides C–I from the seeds of andiroba (Carapa guianensis,Meliaceae)

Five new mexicanolide-type limonoids, carapanolides C–G (1–5), together with two new phragmalin-type limonoids, carapanolides H–I (6, 7), were isolated from the oil of Carapa guianasis AUBLET (Meliaceae) seeds. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR spectra and FABMS. Carapanolides C (1), E (3), and I (7) exhibited moderate activity in the P388 (IC₅₀ 17.9 μM in 1, 15.8 μM in 3) and L1210 cell lines (IC₅₀ 13.3 μM in 1, 18.1 μM in 3, 16.9 μM in 7). On the other hand, Carapanolide D (2) exhibited a strong inhibitory effect in the HL-60 cell line (IC₅₀ 11.0 μM), Carapanolides F (4) showed inhibitory activity in the L1210 cell line (IC₅₀ 15.9 μM), and the cytotoxic activity of Carapanolides I (7) was moderate in all cell lines.     

Cytotoxic 9,19-cycloartane triterpenes from the aerial parts of Cimicifuga yunnanensis

Six new 9,19-cycloartane triterpenes (1–6) were isolated from the aerial parts of Cimicifuga yunnanensis. The new chemical structures were determined by extensive analyses of 1D and 2D NMR spectroscopy. Compounds 1 and 2 are the first 9,19-cycloartane triterpenes characterized by CH₃-18 shifting from C-13 to C-12 in the Cimicifuga spp. The evaluation of inhibition activity against human HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines indicated that compounds 1–6 showed different levels of cytotoxic activities with IC₅₀ values ranging from 1.2 to 27.8 μm.     

Antiproliferative steroidal glycosides from Digitalis ciliata

Two new compounds, a furostanol glycoside (1) and a pregnane glycoside (4), along with eight known compounds, belonging to the classes of spirostane (2,3), pregnane (5–7) and cardenolide (8–10) glycosides, were isolated from the seeds of Digitalis ciliata. Their structures were elucidated by 1D and 2D-NMR experiments as well as ESI-MS analysis. For the first time pregnane glycosides of the diginigenin series have been isolated from D. ciliata. The cytotoxic effects of compounds 1–10 on cell viability of several cancer cell lines, namely human breast cancer (MCF-7), human glioblastoma (T98G), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and human prostate cancer (PC-3) cell lines were evaluated. Compounds 1, 4, 7 and 8 showed antiproliferative effects against MCF-7, HT-29 and A549 cancer cells with IC₅₀ values ranging from 8.3 to 20 μM. The effects of compounds 1–10 on cell proliferation were evaluated on these three cancer cell lines by cell cycle analysis of DNA content using flow cytometry. Compounds 7, 8 and 10 induced significant changes in G₂/M cell cycle phase of all analyzed cells. The obtained results indicate that compounds 7, 8 and 10 are cytostatic compounds effective in reducing cell proliferation by inducing accumulation of the cells in the G₂/M phase of the cell cycle.     

Chemical constituents from Euphorbia stracheyi and their biological activities

Three new diterpenoids, stracheyioids A–C (1–3), as well as 36 known compounds (4–39) were isolated from the whole plants of Euphorbia stracheyi. Compound 1 was a rare 13-deoxy tigliane diterpenoid and compound 2 was an ingenol diterpenoid characterized by an unique 2Z,4Z-decadienoyl acidic moieties. All the known compounds were isolated from E. stracheyi for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1–39 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, Hela and P388) and showed IC₅₀ values in the range 6.64–42.86 μM. The antiangiogenic activities of the isolated compounds were also evaluated using a zebrafish model.     

New cytotoxic diarylheptanoids from the rhizomes of Alpinia officinarum Hance

Two new dimeric diarylheptanoids, named Alpinin C (1) and D (2), a new natural product of diarylheptanoid (3) along with three known diarylheptanoids (4–6) were isolated from the rhizomes of Alpinia officinarum Hance. Their structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR, HRTOFMS, IR). The isolated compounds were evaluated for their cytotoxicity against human tumor cell lines HepG2, MCF-7, T98G and B16-F10. Compound 1 showed selective cytotoxicity against cell lines of MCF-7 and T98G, while compound 6 showed significant cytotoxicity to the all tested tumor cell lines with IC₅₀ in the range from 8.46 to 22.68 μmol/L.     

Lycojaponicuminol A–F: Cytotoxic serratene triterpenoids from Lycopodium japonicum

Six new serratene triterpenoids (1–6), together with nine known triterpenoid compounds were isolated from the extract of club moss Lycopodium japonicum. The structures of isolated compounds were established by spectroscopic methods. The cytotoxic activities of all compounds were evaluated against three human cancer cell lines in vitro by MTT assay. Compounds 2, 6–8 and 11 exhibited moderate activities against all three cell lines with IC₅₀ values of 2.28–11.81 μg/mL.     

Cytotoxic biflavones from Stellera chamaejasme

Bioassay-guided phytochemical studies on Stellera chamaejasme led to the isolation of two new biflavones, chamaejasmenin E (1) and chamaejasmin D (2), together with ten known compounds. The structures of new compounds were elucidated by extensive spectroscopic analyses and their absolute configurations on 2, 3, 2″ and 3″ were confirmed by TDDFT quantum chemical calculated ECD spectra combined with experimental ECD spectra. All isolated biflavones were evaluated for their cytotoxic activities against Bel-7402 and A549 tumor cell lines, and sikokianin D (3) was found to possess the most potential cytotoxic activities against both the two cell lines with IC₅₀ values of 1.29 ± 0.21 and 0.75 ± 0.25 μM, respectively. Moreover, some structure–function relationships of these bioflavones for cytotoxic activities were explored and summarized.     

Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides

Seven new ent-kaurane diterpenoids, isowikstroemins A–G (1–7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1–4 exhibited significant activity with IC₅₀ values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.     

Triterpenes and steroids from the leaves of Aglaia exima (Meliaceae)

A study on the leaves of Aglaia exima led to the isolation of one new and seven known compounds: six triterpenoids and two steroids. Their structures were elucidated and analyzed mainly by using spectroscopic methods; 1D and 2D NMR, mass spectrometry, UV spectrometry and X-ray. All the triterpenoids and steroids were measured in vitro for their cytotoxic activities against eight cancer cell lines; lung (A549), prostate (DU-145), skin (SK-MEL-5), pancreatic (BxPC-3), liver (Hep G2), colon (HT-29), breast (MCF-7) and (MDA-MB-231). The new cycloartane triterpenoid, 24(E)-cycloart-24-ene-26-ol-3-one 1, showed potent cytotoxic activity against colon (HT-29) cancer cell line (IC₅₀ 11.5 μM).     

Bioactive cis-stilbenoids from the tubers of Scirpus yagara

Two new cis-stilbenoids, sciryagarol I (1) and II (2) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds. The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information. The compounds 3, 4 and 6 were isolated for the first time from this genus. Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity. Compounds 1–4 showed significant cytotoxicity against the Hela cell lines with IC₅₀ values ranging from 7.21 to 61.21 μM. 1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79.3 μl/ml for 2, and 152 μl/ml for 1, respectively.     

Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya amabilis

Two new cucurbitane triterpenoids, 7β-hydroxycucurbitacin F-25-O-acetate (1) and 2β,3β,20(S),26,27-pentahydroxy-16α,23(S)-epoxycucurbita-5,24-dien-11-one (2) along with eleven known cucurbitane triterpenoids (3–13, resp.) were isolated from the rhizomes of Hemsleya amabilis Diels. The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of the isolated cucurbitane triterpenoids were evaluated against the HeLa human cancer cell lines. Hemslecin A (5), the main ingredient of H. amabilis, exhibited the significant cytotoxicity with IC₅₀ value of 0.389 μM.