Abietane diterpenoids and other constituents from Clerodendrum trichotomum

The genus Clerodendrum Linn., originally belonging to Verbenaceae, was assigned to Lamiaceae by APG (Angiosperm Phylogeny Group) Ⅱ. Seven abietane diterpenoids (1–7) along with three anthraquinones (8–10) and one neolignan (11) were isolated and identified from the stems of Clerodendrum trichotomum Thunb.. Among them, compounds 4, 6 and 8–11 were reported from the genus Clerodendrum Linn. for the first time. Compounds 1, 3 and 7 were obtained from this species for the first time. Isolation of abietane diterpenoids from C. trichotomum could further comfirm that the genus Clerodendrum belongs to Lamiaceae rather than Verbenaceae.     

Diterpenoids from the roots of Euphorbia ebracteolata and their anti-tuberculosis effects

Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis. The present work has performed the investigation of bioactive chemical substances from the roots of E. ebracteolata. Using various chromatographic techniques, 15 compounds were obtained from the roots of E. ebracteolata. On the basis of widely spectroscopic data analyses, the isolated compounds were determined to be diterpenoids, including rosane derivatives (1–12), isopimarane (13), abietane (14), and lathyrane (15), among which compounds 1–4, and 9 were undescribed previously. The inhibitory effects of isolated diterpenoids against Mycobacterium tuberculosis were evaluated using an Alamar blue cell viability assay. And two rosane-type diterpenoids 3 and 8 displayed moderate inhibitory effects on with the MIC values of 18 μg/mL and 25 μg/mL, respectively. For the potential inhibitor 3, the inhibitory effect against the target enzyme GlmU was evaluated, which displayed a moderate inhibitory effect with the IC₅₀ 12.5 μg/mL. Therefore, the diterpenoids from the roots of E. ebracteolata displayed anti-tuberculosis effects, which would be pay more attentions for the anti-tuberculosis agents.     

Three new abietane diterpenoids from Podocarpus fleuryi

Three new abietane diterpenoids, fleuryinols A–C (1–3), together with fourteen known compounds, were isolated from the twigs and leaves of Podocarpus fleuryi. Their structures were established by spectroscopic analysis, including 1D- and 2D-NMR spectroscopic techniques. Compounds 1–8 were tested cytotoxic activity against five human cancer cell lines, HL-60, SMMC-772, A-549, MCF-7, and SW480, of which fleuryinol B (2) and 19-hydroxyferruginol (4) exhibited moderate cytotoxic activity against some cell lines.     

Eudesmane sesquiterpenoid lactones and abietane diterpenoids from Ajuga forrestii Diels

Four eudesmane sesquiterpenoid lactones (1–4) and seven abietane diterpenoids (5–11) were isolated from the whole plants of Ajuga forrestii. Among them, 3α-acetoxy-1α,8β-dihydroxyeudesm-7(11)-en-8,12-olide (1), 3α-acetoxy-1α-hydroxyl-eudesm-8,7(11)-dien-8,12-olide (2), 1α-acetoxy-8α-oxyethyl-2-oxo-eudesman-3,7(11)-dien-8,12-olide (3) and 2α,3β,11,12-tetrahydroxy-7β,20-epoxy-8,11,13-abietatriene (11) are novel compounds. The structures of compounds 1–11 were determined by spectroscopic analysis. Compound 2 exhibited weak cytotoxicity on HepG2 and MCF-7 cell lines.     

Grayanane diterpenoids from the leaves of Rhododendron dauricum

Phytochemical investigations on the leaves of Rhododendron dauricum L. (Ericaceae) resulted in the isolation of thirteen known grayanane diterpenoids (1–13). Their structures were determined by spectroscopic data analysis and comparison with the literature. The structure and absolute configuration of grayanotoxin VI (1) was determined by single-crystal X-ray diffraction analysis for the first time. This is the first time to report the isolation of grayanane diterpenoids 1–10, 12, and 13 from Rhododendron dauricum. Grayanotoxin VI (1) was isolated from the genus of Rhododendron for the first time. The chemotaxonomic significance of grayanane diterpenoids (1–13) was discussed.     

New ent-kaurane and ent-pimarane diterpenoids from Siegesbeckia pubescens

Phytochemical investigation of the aerial parts of Siegesbeckia pubescens afforded two new ent-kaurane diterpenoids (1-2), together with sixteen known ent-kaurane and ent-pimarane diterpenoids (3–18). Their structures were elucidated on the basis of extensive spectroscopic methods The absolute configurations of 1–2 and 12 were determined by single-crystal X-ray diffraction analyses. All compounds were evaluated for their cytotoxic activities against two human cancer cell lines A375 and HCT-116.     

Semisynthesis of epoxy-pimarane diterpenoids from kirenol and their FXa inhibition activities

Kirenol is one of the biologically active diterpenoids from Siegesbeckia pubescens. In terms of the high content and typical structure, many ent-diterpenoids separated from S. pubescens were presumed to be biologically related to kirenol. Among them, epoxy-pimarane diterpenoids are belonging to a special family of naturally occurring compounds that attracted our attentions on their putative biosynthesis pathway and biological activities. Here, we designed and synthesized two known 14,16-epoxy-pimarane diterpenoids (2 and 3) and five 8,15-epoxy-pimarane diterpenoids (4–8) from kirenol. Their absolute structures were determined by 1D and 2D NMR data and the absolute configurations of 4 were confirmed by X-ray crystallographic data. Their inhibition effects on factor Xa (FXa) were evaluated to assess the potentiality of epoxy-pimarane diterpenoids as FXa inhibitor agents.     

Bioactive phytochemicals from shoots and roots of <Emphasis Type="Italic">Salvia</Emphasis> species

The plants of the genus Salvia L. are important medicinal herbs of the Lamiaceae family and some of them such as S. officinalis (sage), S. miltiorrhiza (red sage, Danshen) and S. sclarea (clary sage) have been used as medicinal plants in the folk medicine of several countries. In this review, we discuss the reports that have examined Salvia species with the aim of isolation of pure compounds with different biological activities. The phytochemical analyses of various sage plants have reported 10 monoterpenoids (1–10), 1 sesquiterpenoid (11), 8 labdane (13–20), 15 ent-kaurane (21–35), 82 abietane, rearranged abietane and tanshinone (36–117), 3 icetexane (118–120), 43 clerodane (121–163), and 3 pimarane (164–166) diterpenoids with cytotoxic and antimicrobial, antiprotozoal, antioxidant, phytotoxic and insecticide effects. The other heavier terpenoids, including 3 sesterterpenes (167–169), 10 triterpenoids and β-sitosterol (170–180) have been introduced as minor bioactive compounds in the sage plants. Sahandinone (107), 6,7-dehydroroyleanone, 7-α-acetoxyroyleanone (40), and tanshinone like diterpenoids have been isolated from the roots’ extracts of different Salvia species. On the other hand, several radical scavenger phenolic compounds like simple phenolics and caffeic acid derivatives (181–201) including rosmarinic acid, flavonoids (202–217) as well as phenolic diterpenoids, such as carnosol and carnosic acid have been isolated from the aerial parts of these plants. One pyrrole (218) and 3 antimicrobial oxylipins (219–221) are among the other less detected constituents in the members of Salvias. Furthermore, sages also synthesize antifungal, antileishmanial and antimalarial phytochemicals in their roots and shoots, which are reviewed in this paper. We also examine the allelopathic phenomena and the ecologically important phytochemicals identified in different parts of the sage plants. Finally, antifeedant and insecticide phenomena, which are due to the presence of volatile monoterpenes and clerodane diterpenes in these plants, are discussed. Considering the presence of diverse biologically active phytochemicals in the sage plants, they can be suggested as suitable candidates for the formulation of valuable natural medicines.     

Three daphnane diterpenoids from Trigonostemon xyphophylloides

Three daphnane diterpenoid trigoxyphins U–W (1–3), together with two known daphnane diterpenoids (4 and 5) were isolated from Trigonostemon xyphophylloides. Their structures were elucidated by spectroscopic analysis. Compound 3 showed modest cytotoxicity against BEL-7402, SPCA-1 and SGC-7901 cancer cell lines.     

NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum

Two new ent-atisane-type diterpenoids (1 and 2), three new lathyrane-type diterpenoids (3–5), and seven known analogues (6–12) were isolated from Euphorbia antiquorum. The structures of these diterpenoids were established by analysis of their NMR, MS, and electronic circular dichroism data. The anti-inflammatory activities were evaluated biologically and compounds 1, 4, 7, 8, and 10 displayed strong NO inhibitory effects with IC₅₀ values less than 40 μM. The potential anti-inflammatory mechanism was also investigated using molecular docking and Western blotting.     

Diterpenoids from the aerial parts of Orthosiphon aristatus var. aristatus

Seven new isopimarane diterpenoids, orthoarisins A?G (1–7), a new secoisopimarane diterpenoid, orthoarisin H (8), a new staminane diterpenoid, orthoarisin I (9), together with 15 previously reported diterpenoids were isolated from the aerial parts of Orthosiphon aristatus var. aristatus. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 13, 17, and 23 showed weak inhibitory activity on the proliferation of the SKOV3, DU145, and PC-3 cell lines.     

Secopieristoxins A and B,two unusual diterpenoids with a new 9,10-secograyanane skeleton from the fruits of Pieris formosa

Phytochemical studies on the fruits of Pieris formosa yielded two new grayanane diterpenoids, secopieristoxins A (1) and B (2), and their structures were elucidated on the basis of extensive analysis of NMR spectra, including two-dimensional NMR techniques. Compounds 1 and 2 were new highly acylated grayanane diterpenoids, of which ring B has suffered an oxidative cleavage between C-9 and C-10.     

Bioactive seco-abietane rearranged diterpenoids from the aerial parts of Salvia prionitis

Five previously undescribed 4,5-seco-abietane rearrange diterpenoids (1–5, Prionidipene A-E) were isolated from the aerial parts of Salvia prionitis, along with thirteen known seco-abietane diterpenoids (6–18). The structures of 1–5 were elucidated mainly based on analysis of NMR and MS data. The absolute configurations of 1–3 were determined by evaluation of experimental and calculated electronic circular dichroism (ECD) spectra. Putative biosynthetic pathways toward the formation of 1 and 2 are proposed. The nitric oxide (NO) production inhibitory effects of all isolates in lipopolysaccharide (LPS)-induced in RAW 264.7 cells were evaluated. Interestingly, compounds 4 and 9 with a furan-ring showed potent inhibitory activity with IC₅₀ values of 14.56 and 15.11 μM, respectively.     

Guanacastane-type diterpenoids from Coprinus plicatilis

Four new guanacastane-type diterpenoids (1–4), named plicatilisins E-H, together with the known compound, plicatilisin D (5), were isloated from two fermentation extracts (i.e., solid state fermentation on PDA medium & static fermentation of malt extract broth culture medium) of the fungal strain Coprinus plicatilis 82. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR as well as FT-ICR-MS, UV, and IR, and comparison with literature data. All the compounds showed insignificant cytotoxicities against the cancer cell line HCT116.     

Cytotoxic clerodane diterpenoids from the leaves of Casearia kurzii

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new clerodane diterpenoids, designated as kurzipenes A–F (1–6), from the leaves of Casearia kurzii. Their structures were elucidated on the basis of NMR spectroscopic data analysis and the absolute configurations were confirmed by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. The cytotoxic activities of compounds 1–6 were evaluated against human lung cancer A549 cell line, human cervical cancer Hela cell line, and human hepatocellular carcinoma HepG2 cell line. Most diterpenoids showed potent cytotoxicities against the three selected cancer cell lines. The preliminary mechanism studies revealed that the most active compound 2, with an IC₅₀ value of 5.3 μM against Hela cells, induced apoptosis and arrested the Hela cell cycle at the G0/G1 stage to exert cytotoxic effects.     

Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4–5, 8–13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1–13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6–10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC₅₀ values between 0.4 μM and 5.9 μM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.     

Terpenoids isolated from Chinese liverworts Lepidozia reptans and their anti-inflammatory activity

Five new terpenoids (1–5) including two dollabellane-type, one ent-kaurane-type diterpenoids and two sesquiterpenoids were isolated from the Chinese liverwort Lepidozia reptans (L.) Dumort., together with nine known terpenoids (6–14). Their structures were determined on the basis of analysis of MS and NMR spectroscopic data, single-crystal X-ray diffraction and electronic circular dichroism calculations. The selected compounds 1, 2, 6, 7, 9 and 14 were screened for anti-inflammatory activities by the model of LPS-induced nitric oxide (NO) production with macrophage cells, and the mechanism of the active compounds 1 and 2 were further explored.     

Cytotoxic abietane-type diterpenoids from twigs and leaves of Croton laevigatus

Seven new abietane-type diterpenoids, crotolaevigatones A–G (1–7), one new aromatic compound, hexyl Z-ferulate (8), along with three known diterpenoids (9–11) and one known aromatic ester, hexyl E-ferulate (12), were obtained from the twigs and leaves of Croton laevigatus. The structures of all isolated compounds were established on the basis of extensive NMR and MS spectroscopic analyses. Compounds 2 and 7 exhibited weak anti-proliferative activity against the A549 and MDA-MB-231 cancer cells, while compound 10 selectively showed significant inhibitory activity against the A549 cancer cells.     

New nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capillipes

Three new nor-clerodane-type furanoditerpenoids, tinocapillins A–C (1–3), and three known diterpenoids were isolated from the rhizomes of Tinospora capillipes. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compound 4 was established by single-crystal X-ray diffraction analysis using Cu Kα radiation. Compounds 1, 2, and 5 exhibited moderate inhibitory activity on the proliferation of the A549, Hep G2, Hela, and OS-RC-2 human cancer cell lines.     

Cytotoxic compounds from invasive giant salvinia (Salvinia molesta) against human tumor cells

Giant salvinia (Salvinia molesta) is one of the most noxious invasive species in the world. Our bioactivity-guided fractionation of ethanol extract of giant salvinia led to the isolation of 50 compounds. Of the six new compounds (1–6), salviniol (1) is a rare abietane diterpene with a new ferruginol-menthol coupled skeleton and both salviniside I (2) and salviniside II (3) are novel benzofuran glucose conjugates with unique 10-membered macrodiolide structures. Sixteen abietane diterpenes (1, 7–17, and 19–22) demonstrated in vitro activities against human tumor cells, and 7 and 8 showed selective cytotoxicity to tumor cells over normal cells.