Terpenoids with potent antimycobacterial activity against Mycobacterium tuberculosis from Trigonostemon reidioides roots

Phytochemical investigation of Trigonostemon reidioides roots led to the isolation of fourteen compounds. These included six new diterpenoids, trigonoreidons A?F (1?6), together with eight known diterpenoids 7?14. The structures of the new compounds were elucidated by spectroscopic techniques and the absolute configuration at the asymmetric carbon was determined by the modified Mosher's method. The structure of trigonoreidon B (2) was confirmed by X-ray crystallographic analysis. The known compounds were identified by comparison of the spectroscopic and physical data with those of reported values. The isolated compounds were evaluated for antimycobacterial activity against Mycobacterium tuberculosis. Among the compounds that exhibited antimycobacterial activity, the diterpenoids rediocide C (12) and rediocide G (14) were the most active compounds, with the MIC value of 3.84 μM.     

Antioxidative Cassane Diterpenoids from the Seeds of Caesalpinia minax

Five new cassane diterpenoids, caesalmins I–M ( 1 – 5 ), and 23 known analogs were isolated from the seeds of Caesalpinia minax. Their structures were elucidated by spectroscopic methods and comparison with reported data. The antioxidant properties of 1 – 28 were determined by the method of oxygen radical absorbance capacity of fluorescein (ORAC‐FL), and 14 compounds exhibited good antioxidant activities with ORAC‐FL values of 2.24–4.89 Trolox equivalents. The structure? activity relationship of the active compounds was also discussed.     

Chemical Composition,Anti-Breast Cancer Activity and Extraction Techniques of Ent-Abietane Diterpenoids from Euphorbia fischeriana Steud

Ent-abietane diterpenoids are the main active constituents of Euphorbia fischeriana. In the continuing search for new anti-breast cancer drugs, 11 ent-abietane diterpenoids (1–11) were isolated from E. fischeriana. The structures of these compounds were clearly elucidated on the basis of 1D and 2D NMR spectra as well as HRESIMS data. Among them, compound 1 was a novel compound, compound 10 was isolated from Euphorbia genus for the first time, compound 11 was firstly discovered from E. fischeriana. These compounds exhibited varying degrees of growth inhibition against the MCF-10A, MCF-7, ZR-75-1 and MDA-MB-231 cell lines in vitro. The experimental data obtained permit us to identify the roles of the epoxy group, hydroxyl group and acetoxyl group on their cytotoxic activities. Extraction is an important means for the isolation, identification, and application of valuable compounds from natural plants. To maximize yields of ent-abietane diterpenoids of E. fischeriana, 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A were selected as quality controls to optimize the salting-out-assisted liquid–liquid extraction (SALLE) by response surface methodology (RSM). The optimized conditions for SALLE were 0.47 g sodium dihydrogen phosphate, 5.5 mL acetonitrile and 4.5 mL water at pH 7.5. The experimental values of 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A (2.134, 0.529, 0.396, and 0.148 mg/g, respectively) were in agreement with the predicted values, thus demonstrating the appropriateness of the model.     

Two New Seco-Labdane Diterpenoids from the Leaves of Callicarpa nudiflora

Two new seco-labdane diterpenoids, nudiflopene N (1) and nudiflopene O (2), and four known compounds were isolated from the leaves of Callicarpa nudiflora. The structures of the new compounds were established by 1D-, 2D-NMR, and HR-ESI-MS spectral analyses. Compounds 1–3 showed inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, and new compounds 1–2 exhibited more potent inhibitory activity than compound 3. The cytotoxicity of compounds 1–3 against human hepatocellular carcinoma HepG2 cells and human gastric carcinoma SGC-7901 cells were evaluated, while all of them exhibited no cytotoxicity.     

Two New Abietane Diterpenoids from the Stems of Clerodendrum kaichianum P. S. Hsu

Two new abietane diterpenoids, named 17‐hydroxyteuvincenone G ( 1 ) and 17‐hydroxyteuvincen‐5(6)‐enone G ( 2 ), together with four known diterpenoids, were isolated from the stems of Clerodendrum kaichianum P. S. Hsu . Their structures were elucidated by extensive NMR and MS analyses, and by comparison with literature data. The new compounds showed significant cytotoxicities against the HL‐60 and A‐549 tumor cell lines.     

Active Substances from Callicarpa nudiflora Exert Anti-Cervicitis Effects and Regulate NLRP3-Associated Inflammation

Luohuazizhu suppository is a Traditional Chinese Medicine used in clinic to treat cervicitis, which is prepared from Callicarpa nudiflora Hook. et Arn (C. nudiflora), an herbal Chinese medicine named Luohuazizhu. This study aimed to figure out the active constituents of C. nudiflora and the potential mechanism for its anti-cervicitis effect. The ethanol extract in C. nudiflora (CNE) and the different fractions of CNE extracted by petroleum ether (CNE-p), dichloromethane (CNE-d), and n-butanol (CNE-b) were tested in vivo for their anti-cervicitis effects. Then the isolated compounds from the CNE-p were tested in vitro for their anti-inflammatory activities. The results displayed that CNE-p, CNE-d, and CNE-b exhibited adequate anti-cervicitis effects, with CNE-p showing the highest efficacy. Further experiment demonstrated that CNE-p could significantly inhibit the expression of NLRP3 in vitro. Six diterpenoids obtained from the CNE-p showed the ability to regulate inflammatory factor levels in vitro. Among these compounds, compounds 1 (callicarpic acid A) and 2 (syn-3,4-seco-12S-hydroxy-15,16-epoxy-4(18),8(17),3(16),14(15)-labdatetraen-3-oic acid) were the most effective agents, and they also inhibited the expression level of NLRP3 in vitro. The results confirmed that C. nudiflora has significant anti-cervicitis effects and the diterpenoids were most likely to be its active components. These data provide scientific support for the clinic usage of Luohuazizhu suppository and the development of new agents in treating cervicitis.     

A new casbane diterpene from Euphorbia pekinensis

A new casbane diterpenoid, referred to as pekinenin G, together with one cembrane diterpene and four known casbane diterpenoids were isolated from the roots of Euphorbia pekinensis. Their structures were elucidated on the basis of spectroscopic studies and comparison with related known compounds. The six compounds showed different cytotoxic activities against four human cancer cell lines.     

Diterpenoids from the fruits of Rhododendron molle, potent analgesics for acute pain

Rhododendron molle G. Don is one of the most potent traditional Chinese medicines for pain relief. Prior investigations have shown that Rhododendrons are rich sources of terpenoids. In our continuing efforts to identify structurally unique and biologically interesting diterpenoids, the fruits of R. molle were collected from Guangxi Province. A chemical study was carried out on the EtOH extract, which led to the isolation of 18 diterpenoids including 12 new compounds. The isolation and structural elucidation of new compounds 1–12, as well as the evaluation of the antinociceptive activities of these compounds were reported.     

Inflammatory and Cytotoxic Activities of Abietane Terpenoids from Nepeta bracteata Benth.

Nepeta bracteata Benth. is used clinically to treat tracheal inflammation, coughs, asthma, colds, fevers, adverse urination, and other symptoms, along with functions in clearing heat and removing dampness. However, there have been few studies characterizing the material basis of its efficacy. Therefore, the aim of this study was to screen for compounds with anti-inflammatory activities in N. bracteata Benth. Using silica gel, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, 10 compounds were separated from N. bracteata Benth. extract, including four new diterpenoids (1–4), one amide alkaloid (5), and five known diterpenoids (6–10). The structures of all the isolates were elucidated by HR-ESI-MS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, we investigated the anti-inflammatory activities of compounds 1–10. It is worth noting that all were able to inhibit nitric oxide (NO) production with IC₅₀ values < 50 μM and little effect on RAW 264.7 macrophage viability. Compounds 2 and 4 displayed remarkable inhibition with IC₅₀ values of 19.2 and 18.8 μM, respectively. Meanwhile, screening on HCT-8 cells demonstrated that compounds 2 and 4 also had moderate cytotoxic activities with IC₅₀ values of 36.3 and 41.4 μM, respectively, which is related to their anti-inflammatory effects.     

New Acyclic 12‐Hydroxygeranylgeraniol‐Derived Diterpenoids from the Seeds of Carpesium triste

Five new acyclic 12‐hydroxygeranylgeraniol‐derived diterpenoids, i.e., 1 – 5 , were isolated from the seeds of Carpesium triste. The structures including the absolute configurations of the new compounds were elucidated by spectroscopic methods. All the compounds, except for 2 , were evaluated for their in vitro cytotoxic activity against cultured SMMC‐7721 (human hepatoma), HL‐60 (human promyelocytic leukemia), and L02 (human hepatocyte) cells.     

Tricyclic diterpenoids of the dolastane ring system from the marine alga dictyota divaricata

Four new oxygenated tricyclic diterpenoids have been isolated from the Caribbean brown alga Dictyota divaricata. The structures of these new compounds were secured by an X-ray analysis of a convenient diol derivative, followed by interconversion where possible. The new diterpenoids belong to the dolastane group first isolated from the herbivorous mollusc Dolabella auricularia and their isolation here indicates that the sea hare most likely derived these compounds from brown seaweeds of the family Dictyotaceae.     

Terpenoids from the liverwort Chandonanthus hirtellus

A new bicyclogermacrane sesquiterpenoid, two new cembrane diterpenoids and five new dolabellane diterpenoids, along with known terpenoids, have been isolated from the Malaysian liverwort Chandonanthus hirtellus. The structures of the new compounds were established by spectroscopic and chemical methods in addition to X-ray crystallographic studies.     

Structurally diverse diterpenoids from Isodon ternifolius collected from three regions

Phytochemical investigation of the aerial parts of Isodon ternifolius from three regions in Yunnan Province afforded 9 new diterpenoids, ternifoliusins A–I (1–9), together with 26 known diterpenoids. Among them, ternifoliusins A–D possess rare 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoid scaffold. The structures of all compounds were determined by comprehensive spectroscopic analysis, as well as quantum chemical calculation methods. Moreover, the molecular constitutions and configurations of ternifoliusins A, E, and F (1, 5, 6) were confirmed by single-crystal X-ray diffraction analysis. Ten compounds were assayed for their cytotoxic activity against the HL-60, SMMC-7721, A-549, MCF-7, and SW-480 human tumor cell lines, and compounds 13, 17, 19, 20, 31 and 34 were demonstrated to be active against all of the five human tumor cell lines.     

Anti-inflammatory diterpenoids from an endophytic fungus Phomopsis sp. S12

Three new pimarane-type diterpenoids, along with two known compounds, were isolated from an endophytic fungus Phomopsis sp. S12. Their structures were determined by comprehensive analyses of HRESIMS, NMR, CD, as well as single-crystal X-ray diffractions. Compound 3 exhibited anti-inflammatory activity against the production of IL-1β and IL-6 induced by lipopolysaccharide (LPS) in macrophages. A putative biosynthetic pathway for compounds 1–5 were also proposed.     

Three New Isoprenylated Flavones from Artocarpus chama Stem and Their Bioactivities

Phytochemical investigation of Artocarpus chama stem was performed by chromatographic techniques, resulting from the isolation and structure elucidation of three new compounds, namely 3′-farnesyl-apigenin (1), 3-(hydroxyprenyl) isoetin (2), and 3-prenyl-5,7,2′,5′-tetrahydroxy-4′-methoxyflavone (3), and five known compounds, namely homoeriodictyol (4), isocycloartobilo-xanthone (5), artocarpanone (6), naringenin (7), and artocarpin (8). From the screening result, A. chama extract showed a potent tyrosinase inhibitory effect. Ihe isolated compounds 1, 4 and 6 also exhibited tyrosinase inhibition with IC₅₀ of 135.70, 52.18, and 38.78 µg/mL, respectively. Moreover, compounds 3, 4, 5, 6, and 8 showed strong activity against Staphylococcus epidermidis, S. aureus, methicillin-resistant S. aureus, and Cutibacterium acnes. This study is the first report on phytochemical investigation with new compounds and biological activities of A. chama. Skin infection can cause dark spots or hyperpigmentation. The isolated compounds that showed both anityrosinase and antimicrobial activities will be further studied in in vivo and clinical trials in order to develop treatment for hyperpigmentation, which is caused by infectious diseases by microorganisms.     

Two new diterpenoids from Plectranthus nummularius Briq

Two new antioxidative diterpenoids, plectranthol A (3)[19-O-(3,4-dihydroxybenzoyl)-11,12-dihydroxy-20(10-->5)-abeo-abieta-1(10),6,8,11,13-tetraene] and plectranthol B (4)[12-O-(3-methyl-2-butenoyl)-19-O-(3,4-dihydroxybenzoyl)-11-hydroxyabieta-8,11,13-trienel along with two known diterpenoids, parvifloron E (1) and F (2) were isolated from the leaves of Plectranthus nummularius Briq. Antioxidative activities of the compounds were measured by the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) method.     

Cassaine diterpenoid dimers isolated from Erythrophleum succirubrum with TRAIL-resistance overcoming activity

Activity-guided fractionation of Erythrophleum succirubrum for TRAIL resistance-overcoming activity led to the isolation of four new cassaine diterpenoid dimers, named erythrophlesins A-D (1-4). Their structures were elucidated by spectral data to show that they have an unsymmetrical dimeric structure through an ester bond between two cassaine diterpenoids. These new compounds were revealed to have a significant reversal effect on TRAIL resistance in human gastric adenocarcinoma (AGS) cells.     

A new bioactive diterpenoid from pestalotiopsis adusta,an endophytic fungus from clerodendrum canescens

Bioassay-guided fractionation of the culture extract of Pestalotiopsis adusta, an endophytic fungus isolated from the medicinal plant Clerodendrum canescens, led to the isolation of one new, (10S)-12,16-epoxy-17(15→16)-abeo-3,5,8,12,15-abietapentaen-2,7,11,14-tetraone (1), and four known diterpenoids, teuvincenone F (2), uncinatone (3), coleon U (4), coleon U-12-methyl ether (5). These structures were identified by using spectroscopic methods, including UV, MS, 1D and 2D NMR experiments. This is the first report of these compounds being isolated from a Pestalotiopsis species. The cytotoxic activities of the compounds were evaluated, and compounds 1 and 3 demonstrated cytotoxic activities against the HL-60 tumour cell line (IC₅₀ ＜ 20 μM).     

Cytotoxic Diterpenoids from the Stem Bark of Annona squamosa L.

Three new ent‐kaurane diterpenoids, (4α)‐19‐nor‐ent‐kaurane‐4,16,17‐triol ( 1 ), (4α,16α)‐17‐(acetyloxy)‐19‐nor‐ent‐kaurane‐4,16‐diol ( 2 ), and 17‐hydroxy‐ent‐kaur‐15‐en‐19‐al ( 3 ), together with 11 known compounds, were isolated from the stem bark of Annona squamosa L. The structures of 1 – 3 were identified by analysis of their spectroscopic data. All compounds were evaluated for cytotoxic activity against human lung cancer (95‐D) and ovarian cancer (A2780) cell lines, and compounds 3, 5, 7, 11 – 14 exhibited promising antiproliferative activities with IC₅₀ values ranging from 0.38 to 34.66 μM .     

Diterpenoids from the Buds of <em>Pinus banksiana</em> Lamb

Three new diterpenoids, namely 7α-hydroxyabieta-8,11,13,15-tetraen-18-oic acid, 7β,15,18-trihydroxyabieta-8,11,13-triene, 13,15-dihydroxypodocarpa-8,11,13-triene, and 12 other known compounds were isolated from buds of Pinus banksiana Lamb. All these compounds, except for 7-oxodehydroabietinol, were isolated for the first time from this plant. Their structures were elucidated by detailed spectroscopic studies and comparison with published data. All isolated compounds were tested for cytotoxic and antibacterial activities. Overall, two compounds, 7-oxodehydroabietinol and 18-nor-4,15-dihydroxyabieta-8,11,13-trien-7-one, showed moderate cytotoxicity against a human lung carcinoma cell line.