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 .     

Daphnane‐Type Diterpenoid Glucosides and Further Constituents of Euphorbia pilosa

Phytochemical investigation of whole plants of Euphorbia pilosa led to the isolation and identification of two new daphnane‐diterpenoid glucosides, euphopilosides A and B ( 1 and 2 , resp.), and a new ent‐abietane, euphopilolide ( 3 ), together with eight known compounds. Compounds 1 and 2 are the first daphnane‐type diterpenoid glycosides. Their structures were elucidated by a combination of 1D‐ and 2D‐NMR, and MS analyses, and acid hydrolysis. Compounds 1 – 9 were evaluated for their in vitro cytotoxicities against five human tumor cell lines, HL‐60, SMMC‐7721, A‐549, MCF‐7, and SW‐480. Compound 7 showed moderate inhibitory activity against all five cell lines.     

Bioactive Tyrosine‐Derived Cytochalasins from Fungus Eutypella sp. D‐1

Three new cytochalasins Z₂₄, Z₂₅, Z₂₆ ( 1 – 3 , resp.) and one known compound, scoparasin B ( 4 ), were isolated from the fungus Eutypella sp. D‐1 isolated from the soil of high latitude of the Arctic. The structures of 1 – 3 were elucidated from spectroscopic data (NMR, MS). These compounds were evaluated for cytotoxic activities against several human tumor cell lines. Among them, compound 1 exhibited moderate cytotoxicity toward human breast cancer MCF‐7 cell line with IC₅₀ of 9.33 μM .     

Four New Tirucallane Triterpenoids from the Fruits of Melia azedarach and Their Cytotoxic Activities

Four new tirucallane triterpenoids, (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxy‐25‐methoxytirucall‐7‐en‐3‐one ( 2 ), (3S,21S,23R,24S)‐21,23‐epoxy‐21,25‐dimethoxytirucall‐7‐ene‐3,24‐diol ( 8 ), (21S,23R,24R)‐21,23‐epoxy‐24‐hydroxy‐21‐methoxytirucalla‐7,25‐dien‐3‐one ( 11 ), and (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxytirucalla‐7,25‐dien‐3‐one ( 12 ), along with 16 known analogues, 1 , 3  –  7 , 9  –  10 , and 13  –  20 , were isolated from the fruits of Melia azedarach. Their structures were elucidated by spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. These compounds were evaluated for their cytotoxicities against HepG2 (liver), SGC7901 (stomach), K562 (leukemia), and HL60 (leukemia) cancer cell lines. Compound 20 exhibited potent cytotoxicity against HepG2 and SGC7901 cancer cells with the IC₅₀ values of 6.9 and 6.9 μm , respectively.     

Diterpenoids and Flavonoids from the Twigs of Cephalotaxus fortunei var. alpina

Three new diterpenoids (a cephalotane, an abietane and a 9(10→20)‐abeo‐abietane) and one new flavonoid, together with 11 known compounds, were isolated from the twigs of Cephalotaxus fortunei var. alpina. The new compounds were identified by comprehensive spectroscopic (including 1D and 2D‐NMR and HR‐ESI‐MS) analysis. Anti‐inflammatory, immunosuppressive and cytotoxic activities of three new compounds were evaluated. 3β,20‐epoxyabieta‐8,11,13‐triene‐3α,12‐diol showed weak cytotoxicity against tumor cell lines NCI?H1975, HepG2, MCF‐7, while fortalpinoid R and 3‐acetonyl‐3,5,7,4′‐tetrahydroxy‐2‐methoxyflavanone were not active at 80 μM. None of these compounds showed anti‐inflammatory and immunosuppressive activities.     

New 4,5‐seco‐20(10→5)‐abeo‐Abietane Diterpenoids with Anti‐Inflammatory Activity from Isodon lophanthoides var. graciliflorus (Benth.) H.Hara

Three new 4,5‐seco‐20(10→5)‐abeo‐abietane diterpenoids, 16‐hydroxysalvilenone ( 1 ), 15‐hydroxysalprionin ( 2 ), and 11β,15‐dihydroxysalprionin‐12‐one ( 3 ), and nine known abietane diterpenoids, 4 – 12 , along with one known sempervirane diterpenoid, hispidanol A ( 13 ), were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus. The structures of compounds 1 – 3 were determined on the basis of spectroscopic methods including extensive analysis of NMR and mass spectroscopic data. All diterpenoids were tested for their TNF‐α inhibitory effects on LPS‐induced RAW264.7 cells. Compound 9 (16‐acetoxyhorminone) was the most potent with an IC₅₀ value of 3.97±0.70 μm .     

Iridoids from Pedicularis verticillata and Their Anti‐Complementary Activity

Three new iridoids named as pediverticilatasin A – C ( 1 – 3 , resp.), together with five known iridoids ( 4 – 8 , resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)‐1‐ethoxy‐1,5,6,7‐tetrahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4(3H)‐one ( 1 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carboxylic acid ( 2 ), (1S,4aS,7R,7aS)‐1‐ethoxy‐1,4a,5,6,7,7a‐hexahydro‐7‐hydroxy‐7‐methylcyclopenta[c]pyran‐4‐carbaldehyde ( 3 ). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1 , 3 , and 6 exhibited anti‐complementary effects with CH₅₀ values ranging from 0.43 to 1.72 mm , which are plausible candidates for developing potent anti‐complementary agents.     

Identification and Biological Evaluation of Secondary Metabolites from the Endolichenic Fungus Aspergillus versicolor

A chemical investigation of the endolichenic fungus Aspergillus versicolor (125a), which was found in the lichen Lobaria quercizans, resulted in the isolation of four novel diphenyl ethers, named diorcinols F–H ( 1 – 3 , resp.) and 3‐methoxyviolaceol‐II ( 4 ), eight new bisabolane sesquiterpenoids, named (?)‐(R)‐cyclo‐hydroxysydonic acid ( 5 ), (?)‐(7S,8R)‐8‐hydroxysydowic acid ( 6 ), (?)‐(7R,10S)‐10‐hydroxysydowic acid ( 7 ), (?)‐(7R,10R)‐iso‐10‐hydroxysydowic acid ( 8 ), (?)‐12‐acetoxy‐1‐deoxysydonic acid ( 9 ), (?)‐12‐acetoxysydonic acid ( 10 ), (?)‐12‐hydroxysydonic acid ( 11 ), and (?)‐(R)‐11‐dehydrosydonic acid ( 12 ), two new tris(pyrogallol ethers), named sydowiols D ( 13 ) and E ( 14 ), and fifteen known compounds, 15 – 29 . All of the structures were determined by spectroscopic analyses, and a number of them were further identified through chemical transformations and electronic circular dichroism (ECD) calculations. Preliminary bioassays of these isolates for the determination of their inhibitory activities against the fungus Candida albicans, and their cytotoxicities against the human cancer cell lines PC3, A549, A2780, MDA‐MB‐231, and HEPG2 were also evaluated.     

Synthesis,Cytotoxicity and Antimicrobial Evaluation of New Coumarin‐Tagged β‐Lactam Triazole Hybrid

A series of coumarin‐tagged β‐lactam triazole hybrids ( 10a – 10o ) were synthesized and tested for their cytotoxic activity against MDA‐MB‐231 (triple negative breast cancer), MCF‐7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK‐293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF‐7 cancer cell lines with IC₅₀ values of 53.55 and 58.62 μm , respectively. More importantly, compounds 10b and 10d were non‐cytotoxic against HEK‐293 cell lines. Structure–activity relationship (SAR) studies suggested that the nitro and chloro group at the C‐3 position of phenyl ring are favorable for anticancer activity, particularly against MCF‐7 cell lines. Furthermore, antimicrobial evaluation of these compounds revealed modest inhibition of examined pathogenic strains with compounds 10c and 10i being the most promising antimicrobial agents against Pseudomonas aeruginosa and Candida albicans, respectively.     

Two New Sesquiterpene Derivatives from the Tunisian Endemic Ferula tunetana Pom.

A new sesquiterpene ester, tunetanin A ( 1 ), a new sesquiterpene coumarin, tunetacoumarin A ( 2 ), together with eight known compounds, i.e., coladin ( 3 ), coladonin ( 4 ), isosmarcandin ( 5 ), 13‐hydroxyfeselol ( 6 ), umbelliprenin ( 7 ) propiophenone ( 8 ), β‐sitosterol ( 9 ), and stigmasterol ( 10 ), were isolated from the roots of Ferula tunetana. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D‐ and 2D‐NMR experiments and MS analysis, as well as by comparison with published data. The cytotoxicity of compounds 1 – 7 towards two human colon cancer cell lines, HT‐29 and HCT 116, was evaluated. Compounds 3, 4 , and 6 showed weak cytotoxic activities.     

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.     

Two New Hydronaphthoquinones from Sinningia aggregata (Gesneriaceae) and Cytotoxic Activity of Aggregatin D

Two new hydronaphthoquinones, aggregatins E and F ( 1 and 2 , resp.) were isolated from the tubers of Sinningia aggregata (Ker‐Gawl .) Wiehler (Gesneriaceae), along with twelve known compounds aggregatin D ( 3 ), tectoquinone ( 4 ), 1‐hydroxy‐2‐methylanthraquinone ( 5 ), icosyl ferulate ( 6 ), pustuline ( 7 ), 1,6‐dihydroxy‐2‐methylanthranquinone ( 8 ), 6‐hydroxy‐2‐methylanthraquinone ( 9 ), 7‐hydroxy‐2‐methylanthraquinone ( 10 ), tyrosol ( 11 ), halleridone ( 12 ), calceolarioside B ( 13 ), and cornoside ( 14 ). All compounds were identified by analysis of spectroscopic and spectrometric data. Compounds 3, 4 , and 10 had already been reported in this species. Compounds 2 and 3 were evaluated against several tumor cell lines, but only 3 exhibited activities against UACC‐62, 786‐0 and OVCAR‐3 cell lines, with IC₅₀ values of 12.3, 12.8 and 0.3 μg/ml, respectively, without toxic effects on non‐cancer cell line HaCat (human keratinocyte).     

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 .     

Biological Evaluation of Secondary Metabolites from the Root of Machilus obovatifolia

Bioassay‐guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B ( 1 ), threo‐(7′R,8′R) and threo‐(7′S,8′S)‐methylmachilusol D ( 2 and 3 ), and isofragransol A ( 4 ), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2 / 3 and 4 / 20 , resp.). The structures were elucidated by spectral analyses. Among the isolates, 1 , licarin A ( 12 ), guaiacin ( 14 ), (±)‐syringaresinol ( 21 ), and (?)‐epicatechin ( 23 ) showed ABTS (=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) cation radical‐scavenging activity, with SC₅₀ values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 μM in 20 min, respectively. In addition, kachirachirol B ( 17 ) showed cytotoxicity against the NCI‐H460 cell line with an IC₅₀ value of 3.1 μg/ml.     

Abietane Diterpenes from Hyptis suaveolens

Investigation of the constituents of the whole plant of Hyptis suaveolens led to the isolation of three new abietane diterpenes, isosuaveolic acid ( 1 ), 8α,9α‐epoxysuaveolic acid ( 2 ), and 14‐O‐methylsuaveolic acid ( 3 ), together with eleven known compounds. The structures of 1 – 3 were established by spectroscopic methods and chemical correlations. Some isolates were tested for their antimycobacterial and cytotoxic activities.     

Two Antiproliferative Triterpene Saponins from Nematostylis anthophylla from the Highlands of Central Madagascar

Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin ( 1 ), and the two new bioactive triterpene saponins 2″‐O‐acetylrandianin ( 2 ) and 6″‐O‐acetylrandianin ( 3 ). The structures of the two new compounds were elucidated based on analysis of their 1D‐ and 2D‐NMR spectra, and mass spectrometric data. The three isolated triterpene saponins displayed moderate but selective antiproliferative activities, with IC₅₀ values of 1.2, 1.7, and 2.2 μM , respectively, against the A2780 ovarian cancer, but only weak inhibitions of the proliferation of A2058 melanoma and the H522 lung cancer cell lines.     

Pinecone of Pinus koraiensis Inducing Apoptosis in Human Lung Cancer Cells by Activating Caspase‐3 and its Chemical Constituents

Pinecones from Pinus koraiensisSiebold & Zucc . (Pinaceae), which have historically been treated as an undesired waste by‐product in the processing of seeds, have recently been shown to contain ingredients with potent biological activities, such as polyphenols exhibiting antitumor activity. With this study, we seek to broaden our understanding of antitumor compounds contained in these pinecones beyond just polyphenols. We found that the water extract of P. koraiensis pinecones exhibits significant cytotoxic activity, with IC₅₀ values ranging from 0.62 to 1.73 mg/ml in four human lung cancer cell lines, A549, H1264, H1299, and Calu‐6, irrespective of their p53 status. We also demonstrate that pinecone water extract induces apoptosis associated with caspase‐3 activation in the same cancer cell lines. Chemical investigation of the pinecone water extract revealed eight main components ( 1  –  8 ), and their structures were identified as dehydroabietic acid ( 1 ), 15‐hydroxy‐7‐oxodehydroabietic acid ( 2 ), 7β,15‐dihydroxydehydroabietic acid ( 3 ), β‐d ‐glucopyranosyl labda‐8(17,13)‐diene‐(15,16)‐lactone‐19‐oate ( 4 ), 7α,15‐dihydroxydehydroabietic acid ( 5 ), (+)‐(1S,2S,4R)‐limonene‐1,2‐diol ( 6 ), sobrerol ( 7 ), and 4‐hydroxybenzoic acid ( 8 ). These findings suggest a novel biological application of P. koraiensis pinecones in combatting human lung cancer, and further identify the major compounds that could contribute to this anticancer activity.     

Novel 3‐Oxo‐ and 3,24‐Dinor‐2,4‐secooleanane‐Type Triterpenes from Terminalia ivorensis A. Chev.

Two new oleanane‐type triterpenes named ivorengenin A (=3‐oxo‐2α,19α,24‐trihydroxyolean‐12‐en‐28‐oic acid; 1 ) and ivorengenin B (=4‐oxo‐19α‐hydroxy‐3,24‐dinor‐2,4‐secoolean‐12‐ene‐2,28‐dioic acid; 2 ), together with five known compounds, arjungenin, arjunic acid, betulinic acid, sericic acid, and oleanolic acid, were isolated from the barks of Terminalia ivorensis A. Chev . (Combretaceae). Their structures were established on the basis of 1D‐ and 2D‐NMR data, and mass spectrometry. A biogenetic pathway to the formation of these compounds from sericic acid, isolated as the major compound from this plant, was proposed. The antioxidant activities of different compounds were investigated by means of the 2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assays, and IC₅₀ values were calculated and compared with Trolox activity. Antiproliferative activities of the isolated compounds were also evaluated against MDA‐MB‐231, PC3, HCT116, and T98G human cancer cell lines, against which the compounds showed significant cytotoxic activities.     

Synthesis of a Natural Chalcone and Its Prenyl Analogs – Evaluation of Tumor Cell Growth‐Inhibitory Activities,and Effects on Cell Cycle and Apoptosis

Six prenyl (=3‐methylbut‐2‐en‐1‐yl) chalcones (=1,3‐diphenylprop‐2‐en‐1‐ones), 2 – 7 , and one natural non‐prenylated chalcone, 1 , have been synthesized and evaluated for their in vitro growth‐inhibitory activity against three human tumor cell lines. A pronounced dose‐dependent growth‐inhibitory effect was observed for all prenylated derivatives, except for 7 . The chalcone possessing one prenyloxy group at C(2′), i.e., 2 , was the most active derivative against the three human tumor cell lines (5.9<GI₅₀<7.7 μM ). The majority of compounds caused an increase in percentage of apoptotic cells and/or they interfered with cell cycle distribution in the MCF‐7 cell line.     

2,5‐Diketopiperazines from the Marine‐Derived Fungus Aspergillus fumigatus YK‐7

Five new diketopiperazines, prenylcyclotryprostatin B ( 1 ), 20‐hydroxycyclotryprostatin B ( 2 ), 9‐hydroxyfumitremorgin C ( 3 ), 6‐hydroxytryprostatin B ( 4 ), and spirogliotoxin ( 5 ), were isolated from the marine‐derived fungus Aspergillus fumigatus YK‐7, along with nine known compounds, 6 – 14 . Their structures were elucidated by spectroscopic methods, and their antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC‐3 cell lines were assessed in vitro. Compounds 10, 12 , and 13 exhibited significant cell growth‐inhibitory activities against U937 cell line, with the IC₅₀ values of 1.8, 0.2, and 0.5 μM , respectively.