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In search for new molecules of diterpene origin with promising anticancer activity, two amino‐derivatives (methyl maleopimarate aminoimide and methyl 1β,13‐epoxydihydroquinopimarate C4‐hydrazone) were involved in the 4‐component Ugi reaction (Ugi‐4CR) and pseudo‐7‐component azido‐Ugi condensation (azido‐Ugi‐7CR) to afford a series of adducts holding α‐aminoacylamide and bis‐1,5‐disubstituted tetrazole substituents. The NCI‐60 cancer cell panel screening revealed diterpene‐type Ugi adducts 2, 5, and 6 with strong antiproliferative potency with GI50 in range of 1.2–15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds. [ABSTRACT FROM AUTHOR]

Plectranthus L'Hér is a large genus of Lamiaceae family comprising of ca. 300 species distributed through the tropical and warm regions of the Old-World, including Africa, from Ethiopia to Tanzania, Asia and Australia. Several species are edible, and some ones have been also used as traditional medicinal of several countries. Phytochemical investigations on non-volatile metabolites of species of this genus indicated them of source of diterpenoids with abietane, phyllocladanes, kaurene skeleton. Plectranthus ornatus Codd. is an invasive, ornamental and traditional medicinal plant native of Central-East Africa, which was spread around the world by Portuguese, especially in the Americas. In the present communication, the aerial parts of P. ornatus, identified wild for the first time in Israel, were analysed for the composition of its essential oil, using gas chromatography–mass spectrometry (GC-MS). Considerations with respect to all the other essential oils of P. ornatus accessions were carried out. [ABSTRACT FROM AUTHOR]

Twelve polyoxygenated cyclohex(a/e)ne diterpene esters, named albiflorenes A–L (1–12), were isolated from the whole plants of Kaempferia albiflora, known as "Prao Mang Mum." Their structures and relative stereochemistry were determined by extensive spectroscopic analysis. Furthermore, the comparison of experimental electronic circular dichroism (ECD) curves with the curves predicted by TDDFT was used to determine the absolute configurations. Albiflorenes contain polyoxygenated cyclohexane (or cyclohexene) derivatives, which are linked to either isopimarane or abietane diterpene acid units. The discovery marks the first occurrence of a conjugate between polyoxygenated cyclohexane (or cyclohexene) rings and diterpenoids. Among the isolates, albiflorene C specifically exhibited antibacterial activity against Bacillus cereus with MIC and MBC values of 3.13 and 6.25 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

Seven new abietane diterpenoids, comprising medusanthol A–G (1–3, 5, 7–9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1–7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1–4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents. [ABSTRACT FROM AUTHOR]

Anisomeles indica (L.) Kuntze (Lamiaceae), commonly called catmint, is an essential oil-bearing herb used in traditional systems of medicine against rheumatism, convulsions, inflammatory skin disorders, and epilepsy. However, the efficacy and mechanism of action of its essential oil against inflammatory conditions remain elusive. The current study aims at the chemical characterization of the essential oil of A. indica leaves (AILEO) and understanding the mechanism of its anti-inflammatory effects by an integrated approach of network pharmacology and in vitro assays. GC–MS analysis of AILEO revealed a total of 30 constituents representing 94.19 % of the total oil. The majority of the chemical groups include diterpene hydrocarbons with abietatriene (58.13 %) and abietadiene (7.18 %) as the major constituents. Out of 30 compounds, 20 passed the ADME screening and were considered as active constituents. A total of 524 compound targets, 409 anti-inflammation targets, and 88 compound-disease intersecting targets were obtained. Multi-level network analysis revealed that the pharmacological mechanisms of alleviation of inflammation by AILEO are due to its interaction with five core inflammatory targets such as PI3K, AKT1, MEK1, ERK1, and RXRA involved in the PI3K-AKT signaling pathway. AILEO did not exhibit any cytotoxic effect on RAW 264.7 cells, but it significantly inhibited nitric oxide (NO) production and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in vitro assays. Further, AILEO enhanced the expression levels of endogenous antioxidant enzymes (CAT, SOD, GPx, and GSH) in comparison to the LPS-induced group. RT-qPCR analysis revealed that AILEO modulated the level of mRNA expression of all five core targets associated with the PI3K-AKT signaling pathway, which further supported the findings of network pharmacology. This study provides valuable insights into the intricate mechanisms by which AILEO exerts anti-inflammatory action indicating its pharmacological potential as a promising candidate for the treatment of disorders linked with inflammation. [Display omitted] • Anisomeles indica leaf essential oil (AILEO) is rich in abietane diterpenoids. • AILEO did not exhibit any cytotoxic effect on RAW 264.7 cells. • Network pharmacology analysis identified 5 key targets linked with PI3K-AKT pathway. • AILEO exerts anti-inflammatory activity by regulating proinflammatory mediators. • AILEO may prove to be a potential agent for the treatment of inflammatory conditions. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of the total synthesis of ferruginol, an aromatic abietane diterpenoid. Ferruginol is known for its unique structure and diverse range of bioactive natural products. The article explores the biological activity of ferruginol, including its antimicrobial, antioxidant, antitumor, and antimalarial properties. It also discusses various synthesis strategies used for ferruginol, such as the Bogert-Cook synthesis and Robinson annulation. The article emphasizes the achievements and methodologies used in the total synthesis of ferruginol, offering valuable insights for researchers in the field. [Extracted from the article]

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5-epi-12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7,5-olide (1), 12-hydroxy-6β-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide (2), 6β,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (4), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (5), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al (6), together with one known abietane diterpenoid, obtuanhydride (3). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 μg/mL, compounds 4, 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively. [ABSTRACT FROM AUTHOR]

The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand–protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819–0.879). Strategic modifications altered HOMO–LUMO gaps (3.39–3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Biofungicides arise as a promising alternative to the indiscriminate use of harmful synthetic fungicides in crop management. Results: The present study reports the bio‐guided fractionation of an endemic plant from the Canary Islands, Salvia canariensis against the phytopathogens, Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum. This procedure allowed identifying a series of diterpenoids with an abietane skeleton (1–5), which exhibited remarkable activity against the phytopathogenic fungi assayed. Their structures were established by means of spectroscopic and spectrometric methods, as well as comparison with reported data. Compounds 2 (carnosic acid), 4 (11‐acetoxy carnosic acid) and 5 (11,12‐diacetoxy carnosic acid) showed significant mycelium growth inhibition (%GI > 50 at 0.1 mg/mL concentration) on all the assayed fungi, and with a potency also higher than the positive control, Fosbel‐Plus, a fungicide commonly used in agriculture. A preliminary structure–activity relationship is also discussed. Conclusions: These findings underline the aromatic abietane diterpenoids as promising eco‐friendly alternatives to conventional fungicides to use in integrated pest management. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

From the aerial parts of Salvia carranzae Zamudio and Bedolla, three new icetexane-type diterpenoids were isolated. Their structures were established through spectroscopic methods and named the following: salvicarranzanolide (1), 19-deoxo-salvicarranzanolide (2) and 19-deoxo-20-deoxy-salvicarranzanolide (3). In addition, the known icetexane-type diterpenoids, 6,7,11,14-tetrahydro-7-oxo-icetexone (4), iso-icetexone (5), 19-deoxo-iso-icetexone (6), icetexone (7), 19-deoxo-icetexone (8) and 7α-acetoxy-6,7-dihydroicetexone (9), were also isolated, along with the abietanes sessein (10) and ferruginol (11). α-Tocopherol was also identified. Compounds 5, 6 and 8 were tested for their antiproliferative activity using the sulforhodamine B assay on six cancer and one normal human cell lines. Diterpenoids 5 and 6 showed noteworthy antiproliferative activity, exhibiting an IC50 (μM) = 0.43 ± 0.01 and 1.34 ± 0.04, respectively, for U251 (glioblastoma), an IC50 (μM) = 0.45 ± 0.01 and 1.29 ± 0.06 for K5621 (myelogenous leukemia), 0.84 ± 0.07 and 1.03 ± 0.10 for HCT-15 (colon cancer), and 0.73 ± 0.06 and 0.95 ± 0.09 for SKLU-1 (lung adenocarcinoma) cell lines. On the other hand, the phytotoxicity of compounds 5–7 and 9–10 was evaluated on seed germination and root growth in some weeds such as Medicago sativa, Panicum miliaceum, Amaranthus hypochondriacus and Trifolium pratense as models. While compounds 5 and 10 exhibited a moderate inhibitory effect on the root growth of A. hypochondriacus and T. pratense at 100 ppm, the diterpenoids 6, 7 and 9 were ineffective in all the plant models. Taxonomic positions based on the chemical profiles found are also discussed. [ABSTRACT FROM AUTHOR]

Synthesis of the natural product prattinin A and some new derivatives has been achieved using abietic acid. The final products and a selection of intermediates were evaluated for their antibacterial activity against three human pathogenic bacteria: E. coli, P. aeruginosa, and S. aureus. The results showed that the antibacterial activity varies depending on the chemical structure of the compounds. Notably, compound 27 exhibited the most potent activity against E. coli and P. aeruginosa, with a minimal inhibitory concentration (MIC) of 11.7 µg/mL, comparable to that of the standard antibiotic ciprofloxacin, and strong activity against S. aureus, with an MIC of 23.4 µg/mL. Furthermore, we assessed the stability of these derivative compounds as potential antimicrobial agents and determined their interactions with the crystal structure of the protein receptor mutant TEM-12 from E. coli (pdb:1ESU) using molecular docking via UCSF Chimera software 1.17.3. The results suggest that 27 has potential as a natural antibiotic agent. [ABSTRACT FROM AUTHOR]

A new biflavone (philonotisflavone-3′′′-methyl ether), three diterpenes (lupulin G, lupulin H, lupulin I), a new ecdysteroid (ajugasterone E), and four known compounds were isolated from the whole plant of Ajuga lupulina Maxim. Their structures were determined by spectroscopic analysis, including MS, NMR and ECD spectral data. Compounds 1-3 has DPPH radical scavenging ability, and compound 1 has stronger activity than vitamin C. Compounds 2, 3, 7 and 8 have potential cytotoxic activity against Hela, with IC50 values less than 20.0 μM. Abietane diterpenes 2, 3, 7 and 8 are also found to have NO inhibitory effects with IC50 values less than 40.0 μM. [ABSTRACT FROM AUTHOR]

We herein report an efficient synthetic method for preparing [6‐7‐6]‐icetexane derivatives. This approach employs our previously designed copper‐catalyzed intramolecular cyclization of enyne‐aryl carbonyl substrates to generate a [6‐6‐6]‐tricyclic abietane framework and a subsequent ring expansion protocol for the [6‐7‐6] scaffold. By synergizing these protocols, we established a highly efficient pathway for synthesizing icetexane compounds from readily available enyne‐aryl starting materials, exhibiting remarkable versatility in accommodating various functional groups while delivering consistently high yields. [ABSTRACT FROM AUTHOR]

The roots of Salvia miltiorrhiza are the source of the traditional Chinese medicine danshen and the class of tanshinones, particular quinoid nor-diterpenoids of the abietane type. Of these compounds, cryptotanshinone, dihydrotanshinone I, tanshinone I, and tanshinone IIA, have been extensively studied for their anticancer potential, not only but as well because of their high abundance in S. miltiorrhiza and their thus easy availability. However, also additional Salvia species are known to contain tanshinones, mainly such of the subgenus Glutinaria, of which S. glutinosa is the only species widely occurring in Europe. Using UHPLC-DAD-MS, the tanshinone profile of S. glutinosa roots collected from two different locations was compared to the profile in S. miltiorrhiza roots. In addition, tanshinone IIA and another six diterpenoids from S. glutinosa were investigated for their antiproliferative and cytotoxic potential against MDA-MB231 and HL-60 cells. Apart from dihydrotanshinone I, which has been previously characterized due to its anticancer properties, we determined danshenol A as a highly antiproliferative and cytotoxic agent, significantly surpassing the effects of dihydrotanshinone I. With regard to the diterpenoid profile, S. miltiorrhiza showed a higher concentration for most of the tanshinones, except for (+)-danshexinkun A, which was present in comparable amounts in both species. Danshenol A, in contrast, was only present in S. glutinosa as were dehydroabietic acid and (+)-pisiferic acid. The results of our study underlines the long traditional use of danshen due to its high amount on tanshinones, but also demonstrates the potential value of investigating closely related species for the discovery of new biologically active lead compounds. [ABSTRACT FROM AUTHOR]

The first stereoselective total synthesis of euolutchuol C using a biomimetic cationic polyene cyclization is demonstrated, and its absolute structure has been established. Four potential stereoisomers of euolutchuol C were synthesized to confirm the structure as an aromatic abietane diterpenoid consisting of 15(S)‐stereogenic center. Asymmetric Sharpless dihydroxylation was employed to construct the chiral epoxide, while CBS‐reduction was utilized for enantiomerically pure benzylic alcohols. A convergent approach is used to synthesize euolutchuol C in seven longest linear steps to give an overall yield of 23 %. [ABSTRACT FROM AUTHOR]

Nepetoideae is the most diverse subfamily of Lamiaceae, and some species are well known for their culinary and medicinal uses. In recent years, there has been growing interest in the therapeutic properties of the species of this group regarding inflammatory illnesses. This study aims to collect information on traditional uses through ethnobotanical, pharmacological, and phytochemical information of the subfamily Nepetoideae related to inflammatory diseases. UNAM electronic resources were used to obtain the information. The analysis of the most relevant literature was compiled and organised in tables. From this, about 106 species of the subfamily are traditionally recognised to alleviate chronic pain associated with inflammation. Pharmacological studies have been carried out in vitro and in vivo on approximately 308 species belonging to the genera Salvia, Ocimum, Thymus, Mentha, Origanum, Lavandula, and Melissa. Phytochemical and pharmacological evaluations have been performed and mostly prepared as essential oil or high polarity extracts, whose secondary metabolites are mainly of a phenolic nature. Other interesting and explored metabolites are diterpenes from the abietane, clerodane, and kaurane type; however, they have only been described in some species of the genera Salvia and Isodon. This review reveals that the Nepetoideae subfamily is an important source for therapeutics of the inflammatory process. [ABSTRACT FROM AUTHOR]

Five abietane diterpenes compounds were separated from petroleum ether extraction sites of ethanol extract of Caryopteris Mongholica, and Compound 1 was identified as a new abietane diterpenes compound by NMR and mass spectrometry, named as Tuurgan A of Caryopteris Mongholica; and Compounds 2-5 separated from Caryopteris Mongholica for the first time were identified as Ferruginol (2), Taxodione (3), Caryopterisoid Q (4), and Huperphlegmarin B (5). The anti-lung cancer activity of the Compounds 1-5 were determined, which results showed that they all had high A549 cytotoxicity. [ABSTRACT FROM AUTHOR]

Plants of the Suregada Roxb. ex Rottler (formerly Gelonium Roxb. ex Willd) are utilized to treat various ailments, namely, hepatic, gum diseases, pyrexia, eczema, and venereal diseases. This review links the reported compounds to ethnomedicinal uses through pharmacological activities. The compounds possess anticancer, anti-allergic, antibacterial, anti-inflammatory, antioxidant, and anti-HIV properties. From the previous reports, 32 known species of the Suregada genus have been investigated morphologically, and nine were investigated for their phytochemistry and pharmacology. Phytochemistry, ethnomedicinal, and pharmacological uses of the other 23 Suregada species are not known and/or not reported. In this review, abietane diterpenoids are the main compounds expressed by the Suregada, accounting for 71 of the 114 reported compounds. Ten triterpenoids and sterols, one aliphatic, two lignans, five flavonoids, and twenty-one nitrogen-containing compounds have been reported from the genus. [ABSTRACT FROM AUTHOR]

Liquidambarines A − C (1−3), three new abietane-type diterpenoids, together with five known compounds (4−8) were isolated from the resin of Liquidambar formosana Hance. Their structures were elucidated by the combination of spectroscopic and computational methods. We explored their anti-inflammatory potential by analyzing the protein expression of iNOS and COX-2. Compounds 1 and 3 exhibit significant anti-inflammatory activities without cytotoxicity. These experimental studies suggest these new abietane-type diterpenoids have the potential to be candidates for inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5-epi-12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7,5-olide (1), 12-hydroxy-6β-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide (2), 6β,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (4), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (5), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al (6), together with one known abietane diterpenoid, obtuanhydride (3). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 μg/mL, compounds 4, 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively.

The biomimetic two-phase strategy employing polyene cyclization and subsequent oxidation/substitution is an effective approach for divergent syntheses of [6-6-6]-tricyclic diterpenes. However, this strategy requires lengthy sequences for syntheses of oxygenated tricyclic aromatic abietane/podocarpane diterpenes owing to the many linear oxidation/substitution steps after cyclization. Here, we present a new synthetic route based on a convergent reverse two-phase strategy employing a reverse radical cyclization approach, which enabled the unified short syntheses of four aromatic abietane/podocarpane diterpenes and the divergent short syntheses of other related diterpenes. Oxygenated and substituted precursors for cyclization were convergently prepared through Friedel-Crafts acylation and rhodium-catalyzed site-selective iodination. Radical redox cyclization using an iridium photoredox catalyst involving neophyl rearrangement furnished the thermodynamically favored 6-membered ring preferentially. (±)-5,6-Dehydrosugiol, salvinolone, crossogumerin A, and Δ5-nimbidiol were synthesized in only 8 steps. An oxygenated cyclized intermediate was also useful for divergent derivatization to sugiol, ferruginol, saprorthoquinone, cryptomeriololide, and salvinolone. Synthesis of the bioactive [6-6-6]-tricyclic diterpene skeleton has been developed using a biomimetic cyclization-oxidation strategy, however, the long oxidation steps hinder the total efficiency of the synthesis. Here, the authors develop a radical cyclization initiated from the C-ring using an oxidation-cyclization strategy in order to shorten the synthesis. [ABSTRACT FROM AUTHOR]

Although vaccines have been developed for rotavirus infections, there is currently no effective therapeutic treatment. Therefore, this study aimed to evaluate the efficacy of 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera (T. nucifera) against bovine G8P[7] and porcine G5P[7] rotaviruses using two different assay strategies: 1) reduction of viral infectivity by neutralizing the virus (virucidal assay) and 2) inhibition of viral replication after infection (post-treatment assay). In the post-treatment assay, compounds 1 and 2 exhibited strong anti-rotavirus activity, with 50% effective concentration values of 24.7 μM (selectivity index; SI= 2.52) and 23.2 μM (SI= 1.75) against bovine G8P[7], 21.1 μM (SI= 2.95) and 22.6 μM (SI= 1.80) against porcine G5P[7], respectively. During viral replication, the two compounds demonstrated stronger inhibition of viral RNA synthesis in the late stages (18 h) than in the early stages (6 h). Compounds 1 and 2 also inhibited the synthesis of viral proteins such as VP6, as determined by immunofluorescence assay. Thus, it appears that compounds 1 and 2 isolated from T. nucifera possess strong antiviral activity against rotaviruses, inhibit viral replication, and may be developed into potential plant-derived therapeutic candidates against rotavirus infection. [ABSTRACT FROM AUTHOR]

A set of 12 abietane diterpene derivatives have been synthesised by the Ugi-four component reaction (Ugi-4CR) and tested for cytotoxicity and activity against influenza virus A/Puerto Rico/8/34 (H1N1) and SARS-CoV-2 pseudovirus. Five dipeptide derivatives demonstrated a selectivity index (SI) higher than 10 and IC50 values from 2 to 32 μM against influenza virus. Compound 11 was found to be a lead with SI of 200, and time-of-addition experiments showed the viral entry into the cell and the binding of the virus to the receptor as a possible target. Compound 7 was the only one showed weak anti-SARS-CoV-2 activity with EC50 value of 80.96 µM. Taken together, our data suggest the potency of diterpene acids-Ugi products as new effective anti-influenza compounds. [ABSTRACT FROM AUTHOR]

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals. [ABSTRACT FROM AUTHOR]

Three new abietane and two new tigliane diterpenoids were isolated from the roots Euphorbia fischeriana. Their structures were elucidated by spectroscopic methods and quantum chemical calculation. Compounds 4 and 5 exhibited the inhibitory activities against human cancer cells HeLa and HepG2, with IC50 ranging from 3.54 to 11.45 µM. [ABSTRACT FROM AUTHOR]

A phytochemical investigation on the petroleum ether partition of the whole plant of Pseudocaryopteris paniculata, yield seven new compounds: one phytanes diterpenoid (2Z,6E,10E) 14-keto-2,6,10-trimethyl pentadeca-2,6,10-trien-1-carboxylic acid (1), five clerodane diterpenoids: paniculatins A-E (2, 3a/3b, 4a/4b), one abietane diterpenoid: ent-uncinatone (5), together with 12 known compounds. Their structures were elucidated on the basis of 1D and 2D Nuclear Magnetic Resonance （NMR_, Infrared Radiation (IR), and mass spectroscopic data. Compound 2, 5, and 11 showed weak selective cytotoxic activity of 11 human cancer cell lines. [ABSTRACT FROM AUTHOR]

[Display omitted] The azido-Ugi reaction of methyl maleopimarate N -(2- aminoethyl) imide with isocyanides, paraformaldehyde and trimethylsilyl azide in one step leads to 1,5-disubstituted diterpene bis-tetrazoles. The compounds demonstrate selective cytotoxicity against NCI-60 cancer cell panel. [ABSTRACT FROM AUTHOR]

The acid treatment of 6,7-seco-abietane dialdehydes gives, in high yield, the corresponding derivatives with the 4a-methyltetrahydrofluorene skeleton of taiwaniaquinoids. A mechanism involving the elimination of formic acid from the cyclic aldol intermediate is proposed here. This process can be postulated as a new biogenetic pathway from abietane diterpenes to taiwaniaquinoids. Using this novel reaction, the first enantiospecific synthesis of bioactive natural cupresol and taxodal has been obtained. [ABSTRACT FROM AUTHOR]

Simple Summary: Abietane diterpenoids are naturally occurring metabolites isolated from a large variety of plants, and many display antitumor properties. Tanshinones are abietane diterpenoids and were first isolated from Salvia miltiorrhiza "tanshen", a well-known traditional Chinese medicine, which has been used extensively for the treatment of coronary heart diseases as well as inflammatory diseases. Tanshinone IIA has shown the inhibition of tumor invasion and metastasis in vitro and in vivo, while abietane carnosol found in rosemary (Rosmarinus officinalis) has also exhibited in vitro and in vivo anticancer activities. However, there are few reports on the pharmacological properties of the structural analogues of both molecules. The aim of this study is to synthesize and to evaluate the antitumor activities of analogues of tanshinone and carnosol. In this study, we found that the analogues were able to inhibit the proliferation of four breast cancer cell lines. Our findings show that these readily available analogues can potentially serve as the foundation of an anti-breast cancer therapeutic agent development platform. The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents. [ABSTRACT FROM AUTHOR]

Among abietane type semisynthetic diterpenoids, a series of quinopimaric and maleopimaric acid derivatives modified at the carboxyl and carbonyl groups, and in ring E were synthesised to obtain new compounds with antimicrobial potency against Mycobacterium tuberculosis H37Rv and key ESKAPE pathogens. It was found that compound 8 exhibited low toxicity to human embryonic kidney cell line HEK-293 (> 32 μg/mL) and showed significant bacteriostatic activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC ≤ 0.25 µg/mL) and excellent antifungal activity against Cryptococcus neoformans var. grubii (MICs ≤0.25 µg/mL) being ≈4 and ≈30 fold more active than vancomycin and fluconazole. It also showed moderate activity against fungus Candida albicans (MIC ≤ 0.25 µg/mL). Compound 9 inhibited M. tuberculosis H37Rv with MIC of 1.25 µg/mL. The docking studies suggest possible interactions of the leading compounds with the molecular targets. [ABSTRACT FROM AUTHOR]

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A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7β-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7β, 20-epoxy-3β, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 μM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 μM. [ABSTRACT FROM AUTHOR]

Two new abietane diterpenoids, phlecarinatone A (1) and phlecarinatone B (2), along with two known analogues (3 and 4), were isolated from Phlegmariurus carinatus. The structures of 1 − 4 were unambiguously elucidated by comprehensive spectroscopic analyses. Abietane diterpenoids were isolated from the plant for the first time. All isolates were tested for their neuroprotective activities against H2O2-induced SH-SY5Y cells injury, and compound 2 showed moderate effect at the concentrations ranging from 5 ∼ 20 μM in vitro assay. [ABSTRACT FROM AUTHOR]

Önemli biyolojik aktiviteye sahip olan diterpenlerin yapısını analiz etmek ve kimyasal özellikleri hakkında öngörüde bulunabilmek amacıyla, abietan iskeletine sahip Szemaoenoid A bileşiği teorik olarak incelenmiştir. Abietan bileşiğinin bağ uzunlukları, bağ açıları, dihedral bağ açıları ve 13C-NMR isotropik kayma değerleri, ab initio ve yoğunluk fonksiyoneli teorisi (YFT) yöntemleriyle hesaplanmıştır. Teorik sonuçların deneysel veriler ile korelasyonu, istatistiksel analiz çalışmalarıyla belirlenmiştir. Titreşim analizleri, B3LYP/cc-pVDZ teori düzeyinde gerçekleştirilmiştir. Ayrıca ilgili bileşiğin elektronik yapıları (HOMO-LUMO ve MEP haritaları) teorik olarak incelenmiştir. Sınır moleküler orbitallerinin enerji değerlerini kullanarak, bileşiğin sınır moleküler orbital enerji farkları, kimyasal sertlik ve elektronegatiflik gibi parametreleri B3LYP/cc-pVDZ düzeyinde hesaplanmıştır. Szemaoenoid A bileşiğinin ortalama kimyasal kararlılık gösterdiği ve reaktifliğe sahip olduğu belirlenmiştir.

Seven undescribed abietane diterpenoids [abietamethinols A-G (1 – 7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1 – 7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 μM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 μM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 μM. Abietamethinols A-G, seven undescribed abietane diterpenoids with unique γ -lactone ring system were isolated from the twigs and leaves of Isodon amethystoides. Among them, compound 4 showed inhibitory effect against Streptococcus sobrinus and AIV respectively. [Display omitted] • Abietane diterpenes (abietamethinols A-G) were isolated from Isodon amethystoides. • Abietamethinols C and D could inhibit the growth of streptococcus sobrinus. • Abietamethinol D was found to inhibit the replication of AIV. • The structures of all isolates were confirmed by the X-ray crystallographic data. • A plausible biosynthetic pathway of abietamethinols A-G was proposed. [ABSTRACT FROM AUTHOR]

Salvia rosmarinus (Lamiaceae), previously known as Rosmarinus officinalis, is a plant cultivated worldwide, native to the Mediterranean region. Its leaves are traditionally used for cooking. This species possesses numerous biological activities, including antioxidant, antimicrobial, anticancer, anti-inflammatory, and hepatoprotective properties. These biological properties are due to the presence of phenolic compounds, including rosmarinic acid and phenolic diterpenoids, such as carnosic acid and carnosol. In this study, we investigated the chemical composition of a green extract obtained by maceration with ethyl lactate for the first time. Seventy-five compounds were tentatively identified by UHPLC–ESI–MS/MS, including six organic acids, six cinnamic acid derivatives, five fatty acids, eighteen flavonoids, and thirty-eight terpenoids. Thus, abietane-type diterpenoids from the ethyl lactate extract were the predominant diterpenoids in the Chilean S. rosmarinus species, in contrast to the Chinese species, in which labdane and isopimarane-type diterpenoids were found for the first time. Finally, our study confirms that the extraction of S. rosmarinus with green ethyl lactate as a solvent is efficient and sustainable for the identification of flavonoids, phenols, and terpenoids from leaves. [ABSTRACT FROM AUTHOR]

Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1β, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the aqueous methanol and butanol extracts of Salvia multicaulis from Jordan resulted in the isolation of 17 compounds including one new abietane diterpene derivative that was identified as 2,20-dihydroxyferruginol. Structural elucidation of all isolated compounds was based on extensive analysis of their spectroscopic data. [ABSTRACT FROM AUTHOR]

Herein, a SnCl4‐catalyzed intramolecular, interrupted homo‐Nazarov cascade biscyclization to access angular (hetero)aryl‐fused polycycles is reported. Subsequent decarboxylation of the readily enolizable products afforded the angular products in up to 71 % yield over two steps, with the trans‐diastereomers as the major products. The cyclopropyl homo‐Nazarov cyclization precursors were formed using a scalable and modular synthetic route that, ultimately, offers access to 6,6,6‐, 6,6,5‐, 6,5,6‐, 6,6,5,6‐, and 6,6,6,5‐fused angular polycyclic products. To showcase the rigor and utility of the method, an 8‐step total synthesis of (±)‐1‐oxoferruginol, an antibacterial aromatic abietane diterpenoid, was disclosed. [ABSTRACT FROM AUTHOR]

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds 1–3, were isolated from Ajuga ovalifolia var. calantha. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound 2 selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound 2 targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound 2 passed the majority of the parameters of common drug discovery rules. Compound 2 restrained A549 proliferation (IC50 = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2–ERK/AKT signaling pathway. Finally, compound 2 (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment. [ABSTRACT FROM AUTHOR]

Two new abietane diterpenoids (4 S, 5 S, 10 S)-12-(β -D-glucopyranosyl)oxy-11-hydroxyabieta-8,11,13-triene-19-oic acid β -D-glucopyranosyl-(1→6)- β -D-glucopyranosyl ester (1) and (3 S, 5 S, 10 S, 15 S)-3 β -[ β -D-glucopyranosyl-(1→6)- β -D-glucopyranosyl]oxy-12-(β -D-glucopyranosyl)oxyabieta-8,11,13-triene-11,16-diol (2), along with 5 known terpene glycosides (3 – 7) were isolated from the n -butanol extract of the stems of Clerodendrum trichotomum Thunb. The structures of the new compounds were determined by analysis of spectroscopic data, chemical correlations, and electronic circular dichroism calculations. Besides, all compounds were evaluated for cytotoxic activities against cultured K562, MCF-7, A549, and HepG2 cell lines. None of them showed good antitumor activities. [ABSTRACT FROM AUTHOR]

The abietane-type diterpenoids are among the most significant diterpene subsets found in hundreds of plant species belonging to various families. Among which, the members of the genus Salvia and Euphorbia are rich in abietane diterpenoids. Because of the chemical diversity and notable bioactivities, such as anticancer, antiinflammatory, antimicrobial, and antioxidant activities, they are attractive. Herein, recent advances in the isolation and characterization of abietanes from natural sources, as well as their biological activities, from 2015 up to 2024 are reviewed. During this time, over 300 abietanes with diverse structures have been discovered., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals.

Extensive research over the past decades has identified numerous phytochemicals that could represent an important source of anti-cancer compounds. There is an immediate need for less toxic and more effective preventive and therapeutic strategies for the treatment of cancer. Natural compounds are considered suitable candidates for the development of new anti-cancer drugs due to their pleiotropic actions on target events with multiple manners. This comprehensive review highlighted the most relevant findings achieved in the screening of phytochemicals for anticancer drug development, particularly focused on a promising class of phytochemicals such as diterpenes with abietane, clerodane, and labdane skeleton. The chemical structure of these compounds, their main natural sources, and mechanisms of action were critically discussed. [ABSTRACT FROM AUTHOR]

Abietane diterpenoids (e.g., carnosic acid, aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol) synthesized in the roots of several Salvia species have proved to have promising biological activities, but their use on a large scale is limited by the very low content extracted from in vivo roots. In this review, we summarized our efforts and the achieved results aimed at optimizing the synthesis of these diterpenes in Salvia sclarea hairy roots by either elicitation or by modifying the expression of genes encoding enzymes of the MEP-pathway, the biosynthetic route from which they derive. Stable S. sclarea hairy roots (HRs) were treated with methyl jasmonate or coronatine, or genetically engineered, by tuning the expression of genes controlling enzymatic rate-limiting steps (DXS, DXR, GGPPS, CPPS alone or in combination), by silencing of the Ent-CPPS gene, encoding an enzyme acting at gibberellin lateral competitive route or by coordinate up-regulation of biosynthetic genes mediated by transcription factors (WRKY and MYC2). Altogether, these different approaches successfully increased the amount of abietane diterpenes in S. sclarea HRs from to 2 to 30 times over the content found in the control HR line. [ABSTRACT FROM AUTHOR]

We report the rearrangement of abietane core with trifluoromethanesulfonic anhydride in pyridine to afford the icetexane core, a key intermediate for total syntheses of the structurally intriguing and biologically active compounds (±)-barbatusol, (±)-rosmaridiphenol, and (±)-pisiferin. [ABSTRACT FROM AUTHOR]