Cytotoxic and Anti‐inflammatory Sesquiterpenes from Ainsliaea henryi

Three new sesquiterpenoids, 4α‐hydroxyeudesm‐11(13)‐en‐12‐yl 3‐methylbutanoate ( 1 ), diaspanolide E ( 2 ), and (13α)‐germacra‐1(10),4‐dien‐12,8α‐olid‐15‐oic acid ( 3 ), along with eight known sesquiterpenoids ( 4 – 11 ), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 – 3 were elucidated by spectroscopic analysis (1D‐, 2D‐NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide‐induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC₅₀ value of 6.54 ± 0.16 μm . Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC₅₀ value of 2.2 ± 0.2 μm .     

Five New C19‐Diterpenoid Alkaloids from Delphinium tianshanicum W.T.Wang

Five new diterpenoid alkaloids, tianshanitines A‐E ( 1  –  5 ), along with ten known compounds ( 6  –  15 ), were isolated from the EtOH extracts of the whole plant of Delphinium tianshanicum W.T.Wang . Their structures were determined based on extensive spectroscopic analyses, including 1D‐ and 2D‐NMR, HR‐ESI‐MS, and the structure of tianshanitine C ( 3 ) was confirmed by X‐ray diffraction analysis. Tianshanitine A ( 1 ) is the first example of natural diterpenoid alkaloid containing a benzoyl group at C(1) position. Tianshanitine B ( 2 ) is a rare natural diterpenoid alkaloid bearing a OH group at C(16) position. Compounds 1  –  5 , 6 , 8 , 10 , 12 and 14 were evaluated for cytotoxicity against HCT116, MCF‐7 and HepG2 human cancer cell lines.     

Synthesis of 9‐(Heteroarylmethylidene)amino Derivatives of Homocamptothecin with Biological Activities

Six 9‐(heteroarylmethylidene)amino derivatives, 2a – 2f , of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a – 2f against three human tumor cell lines, i.e., A‐549, MDA‐MB‐435, and HCT‐116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A‐549 (IC₅₀=0.046 μM ) and HTC‐116 tumor cells (IC₅₀=3.67 μM ), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A‐549.     

Synthesis and Cytotoxicity Evaluation of Panaxadiol Derivatives

In this study, 13 panaxadiol (PD) derivatives were synthesized via reactions with aromatic compounds and amino acids. Following this, the cytotoxicity of these compounds was evaluated against four cancer cell lines (human hepatoma cells HepG‐2, human lung cancer cells A549, human breast cancer cells MCF‐7, and human colon cancer cells HCT‐116) and one normal cell lines (human gastric epithelial cells GES‐1). The results showed that the panaxadiol derivatives 3 , 12 , and 13 showed significant inhibition of cellular proliferation against cancer cells compared with PD, and the panaxadiol derivative 12 had the lowest IC₅₀ value for A549 (IC₅₀=18.91±1.03 μm ). For MCF‐7 cells, most compounds exhibited good inhibition of cellular proliferation, and the panaxadiol derivative 13 showed the strongest inhibitory effect (IC₅₀=8.62±0.23 μm ), which significantly increased the cytotoxicity of PD and was stronger than the positive control (mitomycin). For normal cells, all compounds exhibited low or no toxic effects; thus, these derivatives can be used to develop novel antiproliferative agents.     

Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii

Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as ‘Chuanwu’ and ‘Fuzi’, respectively. Four new C₁₉‐diterpenoid alkaloids, carmichasines A – D ( 1 – 4 ), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds ( 5 – 16 ). Their structures were elucidated via spectroscopic analyses, including HR‐ESI‐MS, IR, and NMR. Carmichasine A ( 1 ) is the first natural C₁₉‐diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C₁₉‐category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF‐7, HCT116, A549, and 786‐0, and none of them showed considerable cytotoxic activity.     

Apoptosis-inducing effect of diketopiperazine disulfides produced by Aspergillus sp. KMD 901 isolated from marine sediment on HCT116 colon cancer cell lines

Aims: Research is to identify the bioactive secondary metabolites produced by Aspergillus sp. KMD 901 isolated from marine sediment and to assess their apoptosis‐inducing effects. Methods and Results: Aspergillus sp. KMD 901 was isolated from marine sediment obtained from the East Sea of Korea. An ethyl acetate extract of KMD 901 exhibited potent cytotoxic activity towards five cancer cell lines (HCT116, AGS, A549, MCF‐7 and HepG2). Sequencing of the internal transcribed spacer (ITS) region in this strain allowed us to identify KMD 901 as a strain of Aspergillus versicolor. The cytotoxic compounds from Aspergillus sp. KMD 901 were purified by reversed‐phase high‐performance liquid chromatography and identified as diketopiperazine disulfides through spectroscopic analyses including extensive 2D NMR and mass spectrometry. The diketopiperazine disulfides were found to induce apoptosis in HCT116 cells based on cell morphology, DNA fragmentation observed by agarose gel electrophoresis, Annexin‐V/PI staining using a flow cytometer and cleavage of poly (ADP‐ribose) polymerase (PARP), caspase‐3, caspase‐8, caspase‐9 and Bcl‐2 family proteins (Bcl‐2, Bcl‐xL and Bax) using Western blotting analysis. Further study using an in vivo xenograft model showed inhibitory effects of acetylapoaranotin ( 2 ) on tumour proliferation. Conclusion: A new diketopiperazine disulfide, deoxyapoaranotin ( 3 ), along with previously described acetylaranotin ( 1 ) and acetylapoaranotin ( 2 ) was separated from Aspergillus sp. KMD 901 and found to have direct cytotoxic and apoptosis‐inducing effects towards HCT116 colon cancer cell lines. Significance and Impact of the Study: These results suggest that the diketopiperazine disulfides produced from Aspergillus sp., KMD 901, could be candidates for the development of apoptosis‐inducing antitumour agents. Also, this study indicates that marine natural products as potential source of pharmaceuticals.     

Chemical Constituents of the Vietnamese Marine Sponge Gelliodes sp. and Their Cytotoxic Activities

A new decenoic acid derivative, gelliodesinic acid, and a naturally new alkaloid, together with three known furanoterpenoids and two known indole alkaloids, were isolated from the MeOH extract of the marine sponge Gelliodes sp. collected in Vietnam. The chemical structures of the isolated compounds were determined by analyses of 1D‐ and 2D‐NMR and MS data and by comparisons of the data with those reported in the literature. The cytotoxicity assay against HeLa, MCF‐7, and A549 cancer cell lines revealed that the three known furanoterpenes exhibited cytotoxic activities with IC₅₀ values ranging from 23.6 to 75.5 μM against the three cell lines, and that 1H‐indole‐3‐carboxylic acid showed cytotoxicity with an IC₅₀ value of 89.2 μM against A549 cancer cell lines.     

A New Cytotoxic Carbazole Alkaloid and Two New Other Alkaloids from Clausena excavata

One new carbazole alkaloid, excavatine A ( 1 ), and two additional new alkaloids, excavatine B ( 2 ) and excavatine C ( 3 ), were isolated from the stems and leaves of Clausena excavata Burm .f. (Rutaceae). Their structures were determined on the basis of detailed spectroscopic analyses, especially 2D‐NMR and HR‐EI‐MS data. Compounds 1 – 3 were tested for their cytotoxic activities against A549, HeLa, and BGC‐823 cancer cell lines, and for their antimicrobial activities against Candida albicans and Staphylococcus aureus. Only 1 exhibited cytotoxicity against A549 and HeLa cell lines with the IC₅₀ values of 5.25 and 1.91 μg/ml, respectively.     

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities

Two new ursane-type triterpenes, eburnealactones A and B ( 1 and 2 ), one new flavonoid, eburneatin A ( 6 ), and one new phenylethanoid glycoside, chiritoside D ( 7 ), along with 9 known compounds ( 3–5 , 8–13 ) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC₅₀ values of 9.57 μM and 8.30 μM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC₅₀ values of 30.70 μM and 38.22 μM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC₅₀ values of 19.69 μM, 16.44 μM, 18.07 μM, 11.51 μM and 18.15 μM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC₅₀ values of 24.06 μM.     

Daturanolide A–C,Three New Withanolides from Datura metel L. and Their Cytotoxic Activities

Three new withanolides ( 1 – 3 ), named as daturanolide A–C, along with six known withanolides ( 4 – 9 ) were isolated from the flowers of Datura metel L. Their structures with absolute configurations were elucidated by a series of spectroscopic methods, electronic circular dichroism (ECD) analyses, and X‐ray crystallography. All the isolates were evaluated for cytotoxicity against five human cancer cell lines (HCT116, U87‐MG, NCI‐H460, BGC823, and HepG2), and 6 exhibited marked cytotoxicity.     

Two new lignans from Gymnotheca chinensis Decne

Two new lignans, gymnothelignans V (1) and W (2), were isolated from a methanol extraction of Gymnotheca chinensis Decne. Their structures were established on the basis of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited moderate cytotoxicity against the HCT116, HCT15, A549, MCF-7 and HepG2 cancer cell lines with IC₅₀ values of 45.1 μM, 26.9 μM, 49.6 μM, 30.0 μM and 49.7 μM, respectively. Compound 2 exhibited weak cytotoxicity against the A549 cancer cell line with an IC₅₀ value of 41.3 μM.     

Triterpenoids from Meehania fargesii with Cytotoxic Activity1

In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure–activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.     

Six new dihydrobenzofuran lignans from the branches and leaves of Illicium wardii and their cytotoxic activities

Six new dihydrobenzofuran lignans, named illiciumlignans A⿿F (compounds 1⿿6), along with 15 known compounds (7⿿21) were isolated from the branches and leaves of Illicium wardii. The structures of 1⿿6 were determined using a combination of 1D and 2D NMR, HR-ESI⿿-MS, and CD spectroscopic data. Illiciumlignan D (4) is the first reported dihydrobenzofuran lignan arabinofuranoside that is derivatized with the arabinofuranose moiety on C-9⿲. Compounds 1⿿21 were evaluated for cytotoxic activity against four human cancer cell lines. Compounds 8, 12 and 20 exhibited significant activity against human cancer cell lines (A549, SKOV3, HepG2 and HCT116), with IC₅₀ values ranging from 2.7 to 14.9 μM.     

BAI,A novel cyclin‐dependent kinase inhibitor induces apoptosis in A549 cells through activation of caspases and inactivation of Akt

Previously, we have synthesized a novel cyclin‐dependent kinase (CDK) inhibitor, 2‐[1,1′biphenyl]‐4‐yl‐N‐[5‐(1,1‐dioxo‐1λ⁶‐isothiazolidin‐2‐yl)‐1H‐indazol‐3‐yl]acetamide (BAI) and reported its anti‐cancer activity in head and neck cancer cells. In this study, we further evaluated the effect of BAI on growth of various human cancer cell lines, including A549 (nonsmall cell lung cancer), HCT116 (colon), and Caki (kidney). Profoundly, results of XTT and clonogenic assays demonstrated that BAI at nanomolar concentrations (20–60 nM) inhibited growth of A549, HCT116, and Caki cells, suggesting the anti‐cancer potency. We show that BAI induced a dose‐dependent apoptotic cell death in these human cancer cells, as measured by fluorescence‐activated cell sorting (FACS). Interestingly, further biochemical analysis showed that treatment with BAI at 20 nM induced apoptosis in A549 cells in association with activation of caspases, cleavage of phospholipase C‐γ1 (PLC‐γ1), and inhibition of Akt in A549 cells. Importantly, pharmacological inhibition study revealed that pretreatment with z‐VAD‐fmk, a pan caspase inhibitor strongly blocked the BAI‐induced apoptosis in A549 cells. Transfection analysis with Akt cDNA encoding constitutively active Akt further addressed the significance of Akt inhibition in the BAI‐induced apoptosis in A549 cells. Notably, disruption of the PI3K/Akt pathway by LY294002, a PI3K/Akt inhibitor potentiated apoptosis in A549 cells by BAI at a subcytotoxic concentration. These findings collectively suggest that BAI potently inhibits growth of A549, HCT116, and Caki cells, and that the BAI‐induced apoptosis in A549 cells is associated with activation of caspases, and inhibition of Akt. J. Cell. Biochem. 114: 282–293, 2013. © 2012 Wiley Periodicals, Inc.     

Design,synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives

Two series of moscatilin derivatives were designed, synthesized and evaluated as anti-tumor and anti-angiogenesis agents. Most of these compounds showed moderate-to-obvious cytotoxicity against five cancer cell lines (A549, HepG2, MDA-MB-231, MKN-45, HCT116). Among these cell lines, compounds had obvious effects on HCT116. Especially for 8Ae, the IC₅₀ was low to 0.25 μM. 8Ae can inhibit the viability and induce the apoptosis of HCT116 cells but exhibit no cytotoxic activity in noncancerous NCM460 colon cells. 8Ae can also arrest the G2/M cell cycle in HCT116 cells by inhibiting the α-tubulin expression. Zebrafish bioassay-guided screen showed the 22 moscatilin derivatives had potent anti-angiogenic activities and compound 8Ae had better activities than positive compound. Molecular docking indicated 8Ae interacted with tubulin at the affinity of −7.2 Kcal/mol. In conclusion, compound 8Ae was a potential antitumor and anti-angiogenesis candidate for further development.     

Phenolic derivatives with cytotoxic activities from the roots of Fallopia multiflora var. ciliinervis

Fourteen phenolic derivatives including two new compounds (1, 2), one new natural product (10) and eleven known ones (3 - 9 and 11–14) were obtained from the roots of Fallopia multiflora var. ciliinervis. The structures were determined using IR, MS, 1D and ²D NMR spectroscopy and the absolute configuration of the new structure (2) was deduced by ECD experiments. All of the isolated compounds were assayed for their cytotoxic activities against three tumor cell lines (A549, HCT116 and SW620) and the results showed that compounds 12－14 showed cytotoxicities against A549 cells while compounds 10 and 11 showed cytotoxicities against SW620 cells.     

Iridoids and lignans from Valeriana officinalis L. and their cytotoxic activities

Two new iridoids (1 and 2), one new lignan (3) together with one known iridoid (4) and twelve known lignans (5－16) were obtained from the roots of Valeriana officinalis L. (V. officinalis). The structures were determined using IR, MS, ¹D and ²D NMR spectroscopy and the absolute configurations of the new structures were deduced by ECD experiments. All of the isolated compounds were assayed for their cytotoxic activities against three tumour cell lines (A549, HCT116 and SW620) and the results showed that compounds 9 and 10 showed cytotoxicities against A549 cells, compounds 9 and 11 showed cytotoxicities against SW620 cells and compound 10 showed cytotoxicities against HCT116 cells.     

New Glycerolipids from the Traditional Chinese Medicine of Syngnathus acus (Hai-Long)

Two new glycerolipids, syngaculipids A and B ( 1 and 2 ), one first naturally occurring metabolite ( 8 ), together with five known compounds ( 3 – 7 ) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116 cell lines. Compound 8 exhibited moderate cytotoxicity with IC₅₀ values of 34.5 and 38.9 μM on the A549 and HCT-116 cell lines, respectively.     

Monalbidins A–E,Decalins with Potential Cytotoxic Activities from Marine Derived Fungus Monascus albidus BB3

Five new decalins, monalbidins A–E ( 1 , 2 and 7–9 ), together with 16 known compounds ( 3 – 6 and 10–21 ), were isolated from the AcOEt extract of marine derived fungus Monascus albidus BB3 cultured in GPY medium. Among the known compounds, 1-hydroxymonacolin L ( 11 ), dehydromonacolin J ( 15 ), 8-O-acetylmonacolin J ( 19 ) and O-acetylmonacolin K ( 21 ) were separated from natural sources for the first time. Their structures were determined by comprehensive analysis on the 1D and 2D NMR, HR-ESI-MS, UV and IR data, and their absolute configurations were assigned by experimental and calculated ECD data, and X-ray single-crystal diffraction analysis. Monalbidins C and D ( 7 and 8 ), monacolin K methyl ester ( 13 ), dehydromonacolin L ( 14 ), dehydromonacolin K ( 16 ), monacolin K ( 20 ) and O-acetylmonacolin K ( 21 ) showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, HCT116 and MDA-MB-231.     

Chemical Constituents of Crinum asiaticum L. var. sinicum Baker and Their Cytotoxic Activities

A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum Baker resulted in the isolation of two new alkaloids, asiaticumines A and B ( 1 and 2 , resp.), together with 21 known compounds, including nine alkaloids, four amides, five phenolic compounds, and three flavonoids. All 23 compounds were isolated for the first time from Crinum asiaticum L. var. sinicum Baker . Their structures were elucidated by spectroscopic methods. In addition, ten alkaloids, 1 – 10 , were evaluated for their cytotoxic activities against human tumor cell lines A549, LOVO, HL‐60, and 6T‐CEM. Compounds 3, 4 , and 7 – 10 selectively showed remarkable inhibition against one or more of the tested cell lines.