Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan

Three new cytochalasins Z₂₁–Z₂₃ ( 1 – 3 , resp.), together with five analogs, 4 – 8 , were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L ‐ and D ‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z₂₁ and Z₂₂ ( 1 and 2 , resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 8.2, 20.0, and 3.1 μM , respectively.     

Cytotoxic ent‐Kaurane Diterpenoids from Isodon nervosus

Four new ent‐kaurane diterpenoids, rabdonervosins G–J ( 1 – 4 , resp.), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated by extensive spectroscopic analyses, including 1D‐, 2D‐NMR and HR mass spectra. Compound 2 showed potent cytotoxicity against the HepG2 and PC‐9/ZD cell lines with IC₅₀ values of 2.36 and 6.07 μM , respectively, and compound 3 exhibited cytotoxicity against the HepG2 and CNE2 cell lines with IC₅₀ values of 8.64 and 9.77 μM , respectively.     

Pierisformotoxins A – D,Polyesterified Grayanane Diterpenoids from Pieris formosa and Their cAMP‐Decreasing Activities

Four highly acylated diterpenoids, designated as pierisformotoxins A–D ( 1 – 4 , resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B ( 1 and 2 , resp.) were new highly acylated grayanane diterpenoids, of which the five‐membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five‐membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP‐regulation‐activity assay showed that pierisformotoxin C ( 3 ) at 10 μM (inhibitory ratio (IR): 10.1%) or 2 μM (9.8%), and pierisformotoxin B ( 2 ) at 50 μM (13.9%) significantly decreased the cAMP level in N1E‐115 neuroblastoma cells (p<0.05).     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Lobophytones U - Z₁, biscembranoids from the Chinese soft coral Lobophytum pauciflorum

Chemical examination of a Chinese soft coral Lobophytum pauciflorum resulted in the isolation of seven new biscembranoids named lobophytones U–Z₁ ( 1 – 7 , resp.), together with methyl sartortuoate ( 8 ) and nyalolide ( 9 ). The structures of the new compounds were elucidated by 1D‐ and 2D‐NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analysis in association with MS and IR data. All compounds were tested against lipopolysaccharide (LPS)‐induced nitric oxide (NO) release in mouse peritoneal macrophage. Lobophytone Z ( 6 ) inhibited NO production with an IC₅₀ value of 2.6 μM . Lobophytone H ( 1 ) showed inhibitory activities against the bacteria S. aureus and S. pneumoniae.     

Phenolic compounds from the whole plants of Gentiana rhodantha (Gentianaceae)

Gentiana rhodantha Franch. ex Hemsl. (Gentianaceae), an annual herb widely distributed in the southwest of China, has been medicinally used for the treatment of inflammation, cholecystitis, and tuberculosis by the local people of its growing areas. Chemical investigation on the whole plants led to the identification of eight new phenolic compounds, rhodanthenones A–D ( 1 – 4 , resp.), apigenin 7‐O‐glucopyranosyl‐(1→3)‐glucopyranosyl‐(1→3)‐glucopyranoside ( 5 ), 1,2‐dihydroxy‐4‐methoxybenzene 1‐O‐α‐L ‐rhamnopyranosyl‐(1→6)‐β‐D ‐glucopyranoside ( 6 ), 1,2‐dihydroxy‐4,6‐dimethoxybenzene 1‐O‐α‐L ‐rhamnopyranosyl‐(1→6)‐β‐D ‐glucopyranoside ( 7 ), and methyl 2‐O‐β‐D ‐glucopyranosyl‐2,4,6‐trihydroxybenzoate ( 8 ), together with eleven known compounds, 9 – 19 . Their structures were determined on the basis of detailed spectroscopic analyses and chemical methods. Acetylcholinesterase (AChE) inhibition and cytotoxicity tests against five human cancer cell lines showed that only rhodanthenone D ( 4 ) and mangiferin ( 12 ) exhibited 18.4 and 13.4% of AChE inhibitory effects at a concentration of 10⁻⁴ M , respectively, while compounds 1 – 5 and the known xanthones lancerin ( 11 ), mangiferin ( 12 ), and neomangiferin ( 13 ) displayed no cytotoxicity at a concentration of 40 μM .     

Tirucallane Triterpenoids from the Stems of Brucea mollis

Three new tirucallane triterpenoids, brumollisols A–C ( 1 – 3 , resp.), together with five known analogues, (23R,24S)‐23,24,25‐trihydroxytirucall‐7‐ene‐3,6‐dione ( 4 ), piscidinol A ( 5 ), 24‐epipiscidinol A ( 6 ), 21α‐methylmelianodiol ( 7 ), and 21β‐methylmelianodiol ( 8 ), were isolated from an EtOH extract of the stems of Brucea mollis. Their structures were elucidated by means of spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC‐823 cancer cells with IC₅₀ values of 1.16 and 3.01 μM , respectively. At a concentration of 10 μM , compounds 1 – 5, 7 , and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39.8±7.7 to 68.2±4.5%.     

Cuceolatins A–D: New Bioactive Diterpenoids from the Leaves of Cunninghamia lanceolata

Four new diterpenoids named cuceolatins A–D, including three labdane‐type ( 1 – 3 ) and one abietane‐type ( 4 ) as well as three known labdane analogs ( 5 – 7 ), were reported from the leaves of Cunninghamia lanceolata. Structural assignments for these compounds were conducted by analyses of spectroscopic data, and their absolute configurations were determined by time‐dependent density functional theory (TD‐DFT) based electronic circular dichroism (ECD) calculations. Among them, the abietane‐type diterpenoid (11‐hydroxy‐12‐methoxyabieta‐8,11,13‐trien‐3‐one ( 4 )) showed significant cytotoxicity against human MDA‐MB‐231, MCF‐7, and HeLa tumor cell lines with IC₅₀ measurements of 4.3, 2.8 and 4.5 μm , respectively, while the labdane‐type diterpenoids with a 4α‐carboxy group ( 1 – 3 and 5 ) exhibited moderate antibacterial activity towards Bacillus subtilis and Staphylococcus aureus with IC₅₀ values all below 25 μm .     

Bioactive Xenicane Diterpenoids from the Taiwanese Soft Coral Asterospicularia laurae

Chemical investigation of the Taiwanese soft coral Asterospicularia laurae has led to the isolation of three new xenicane diterpenoids, named asterolaurins K–M ( 1 – 3 , resp.). Their chemical structures were determined through extensive spectroscopic analyses (¹H‐ and ¹³C‐NMR, ¹H,¹H‐COSY, HMBC, and NOESY). Compound 2 exhibited cytotoxic activity against HEp‐2, Daoy, MCF‐7, and WiDr tumor cells.     

New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha

Two new labdane‐type diterpenes (adenanthic acids A and B; 1 and 2 , resp.) and three new labdane diterpene glycosides (adenanthosides A–C; 3 – 5 , resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids ( 6 – 12 ), eight triterpenoids ( 13 – 20 ), one lignan glycoside ( 21 ), six steroids ( 22 – 27 ), and one ceramide ( 28 ). Their structures were elucidated by spectroscopic methods including extensive 2D‐NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities.     

Hypofolins A – L,ent‐Labdane Diterpenoids from the Roots of Hypoestes phyllostachya ‘Pink Splash’

Twelve new ent‐labdane diterpenoids, hypofolins A – F ( 1 – 6 ) and hypofolins G – L ( 7a / 7b , 8a / 8b , and 9a / 9b ), were isolated from the roots of Hypoestes phyllostachya ‘Pink Splash’. Their structures were elucidated by extensive 1D‐ and 2D‐NMR spectroscopic and HR‐MS data. The absolute configurations of 1 , 2 , 5 , and 7a / 7b were determined by single crystal X‐ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a / 7b , 8a / 8b , and 9a / 9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC‐7721 cell line with IC₅₀ value of 31.40 μm .     

Immunosuppressive Withanolides from Withania coagulans

Six new withanolides, withacoagulins A–F ( 1 – 6 , resp.), together with ten known withanolides, 7 – 16 , were isolated from the aerial parts of Withania coagulans. Their structures were determined by spectroscopic techniques including 1D‐ and 2D‐NMR (¹H, ¹³C, HMQC, and HMBC) and MS experiments. These compounds, including the crude extracts of this herb, exhibited strong inhibitory activities on the T‐ and B‐cell proliferation.     

abeo‐Taxane Diterpenoids from the Taiwanese Yew Taxus sumatrana

Chemical investigation of the acetonic extract of the leaves and twigs of Taxus sumatrana (Taxaceae) led to the isolation of four new taxane diterpene esters, taiwantaxins A–D ( 1 – 4 , resp.). Their structures were determined primarily on the basis of 1D‐ and 2D‐NMR techniques as well as MS. Compound 1 is a rearranged taxane diterpenoid possessing an opened oxetane ring moiety containing C(4), C(5), and C(20). The metabolites 2 and 3 belong to a 5/6/6 taxene system having a rare five‐membered γ‐lactone ring comprising C(8), C(9), C(10), and C(19). Compound 4 is an example of a taxane diterpene containing a 6/8/6 ring system with a tetrahydrofuran ring comprising C(2), C(3), C(4), and C(20). The 11(15→1)abeo‐taxane diterpenoids, taiwantaxins A–C ( 1 – 3 , resp.) are lacking an O‐bearing functionality at either C(13) or C(14). Compound 2 showed significant cytotoxic activity against human PC‐3 tumor cells.     

Triterpene Saponins from the Roots of Ilex asprella

Six new triterpene saponins, ilexasprellanosides A–F ( 1 – 6 , resp.), together with eleven known compounds were isolated from the roots of Ilex asprella. The new saponins were characterized as ursa‐12,18‐dien‐28‐oic acid 3‐O‐β‐D ‐xylopyranoside ( 1 ), 19α‐hydroxyursolic acid 3‐O‐β‐D ‐(2′‐O‐acetylxylopyranoside) ( 2 ), 19α‐hydroxyursolic acid 3‐O‐β‐D ‐glucuronopyranoside ( 3 ), 3β,19α‐dihydroxyolean‐12‐en‐23,28‐dioic acid 28‐O‐β‐D ‐glucopyranoside ( 4 ), 19α‐hydroxyoleanolic acid 3‐O‐β‐D ‐(2′‐O‐acetylxylopyranoside) ( 5 ), 19α‐hydroxyoleanolic acid 3‐O‐β‐D ‐glucuronopyranoside ( 6 ). The structures of the new compounds were elucidated by analysis of their spectroscopic data and chemical degradation. Compounds 2, 4 , oleanolic acid 3‐O‐β‐D ‐glucuronopyranoside, 3‐β‐acetoxy‐28‐hydroxyurs‐12‐ene, and pomolic acid showed significant cytotoxic activities against human tumor cell line A549 (IC₅₀ values of 1.87, 2.51, 1.41, 3.24, and 5.63 μM , resp.).     

Sinuladiterpenes A–F,New Cembrane Diterpenes from Sinularia flexibilis

Chromatographic investigation of the octocoral Sinularia flexibilis afforded six new cembrane diterpenes, sinuladiterpenes A–F ( 1 – 6 , resp.), in addition to four known cembranolides, 11‐episinulariolide acetate, 11 ‐ dehydrosinulariolide, 11‐episinulariolide, and sinulariolide. Their structures were elucidated by spectroscopic analysis, especially 2D‐NMR and HR‐ESI‐MS. Compound 2 exhibited significant in vitro cytotoxic activity against human colon adenocarcinoma (WiDr) cell line.     

Diterpenoids from Euphorbia neriifolia and Their Related Anti‐HIV and Cytotoxic Activity

Fifteen diterpenoids ( 1 – 15 ), including three undescribed ones with ent‐atisane skeleton, eupnerias G–I ( 1 – 3 ), were obtained from Euphorbia neriifolia. Compounds 1 – 3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti‐HIV‐1 effect, and their EC₅₀ were 6.6±3.2 and 6.4±2.5 μg mL^?1, respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC₅₀ at 13.70 and 15.57 μm , respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC₅₀=0.01 μm ), while it did not show any cytotoxicity against HepG2/Adr cell lines.     

Diterpenoids and a Diarylheptanoid from Hedychium coronarium with Significant Anti‐Angiogenic and Cytotoxic Activities

Two new labdane diterpenoids, namely hedycoronals A and B ( 1 and 2 , resp.), were isolated from the rhizomes of Hedychium coronarium, together with eight known diterpenoids, 4 – 11 , and a known diarylheptanoid, 3 . The structures of 1 and 2 were established by detailed interpretation of their 1D‐ and 2D‐NMR spectra and HR‐ESI‐MS data. Inhibitory activities against human umbilical vein endothelial cells (HUMECs) proliferation and cytotoxic activities against four cancer cell lines were assessed for all the isolates. Most of these metabolites showed moderate or potent cytotoxic activities against four cancer cell lines. Moreover, compounds 3 and 8 exhibited promising inhibitory activities against HUMECs with the IC₅₀ values of 6.4 to 3.3 μM .     

Novel Zierane‐ and Guaiane‐Type Sesquiterpenes from the Root of Melicope denhamii

Two novel zierane‐type sesquiterpenes, named melicodenones A and B ( 1 and 2 , resp.), and three new guaiane‐type sesquiterpenes, named melicodenones C–E ( 3 – 5 ), were isolated from the root of Melicope denhamii (Seem. ) T. G. Hartley together with zierone ( 6 ). Their structures were established by extensive NMR‐spectroscopic analyses. Compounds 1 – 6 were tested for cytotoxicity using human colon cancer DLD‐1 cells, and melicodenone A ( 1 ) was found to exhibit moderate activity.     

Ficuschlorins A - D, lactone Chlorins from the leaves of ficus microcarpa

Four new lactone chlorins, ficuschlorins A – D ( 1 – 4 , resp.), and six known pheophytins were isolated from the leaves of Ficus microcarpa. The structures of these compounds were determined by 1D‐ and 2D‐NMR spectroscopy, and other techniques. New natural pheophytins were rarely obtained. In the past ten years, only three new pheophytins were isolated from natural sources.     

neo-Clerodane Diterpenoids from the Aerial Parts of Scutellaria barbata with Anti-Inflammatory Activity

The bioactivity-guided isolation on the Scutellaria barbata extract resulted in the purification of four undescribed neo-clerodane diterpenoids, scuttenlines A–D ( 1 – 4 ), alone with 20 known diterpenoids ( 5 – 24 ). The chemical structures of them were elaborated by extensive spectroscopic means, including 1D, 2D-NMR and HR-MS. The anti-inflammatory potential ability of 1 – 24 was screened in lipopolysaccharide-stimulated mouse RAW 264.7 cells. Scuttenline C (IC₅₀=1.9 μM) and 18 (IC₅₀=3.7 μM) exhibited potent activity to inhibit NO production.