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Objective: The increasing social significance of antitumor drugs is associated with the high prevalence of oncological diseases and determines the need to search for and create new effective drugs. This study aims to synthesize, characterize, and evaluate the cytotoxicity potential of diterpene esters and amides (I–XIII) and (XVII–XIX). Methods: The acid chloride method was used to synthesize 1-, 1,4-, and 1,4,20- derivatives of methyl dihydroquinopimarate containing furan and indoleacetyl fragments (I–V) and C20-amides of dihydroquinopimaric and maleopimaric acids containing linear, heterocyclic, and aromatic amine fragments (VI–XIII). The reaction of diethyl chlorophosphite with dihydroquinopimaric alcohols proceeds in the presence of dimethylaminopyridine in pyridine to give diethoxyphosphoryl derivatives (XVII–XIX). The structures of the synthesized compounds were confirmed by mass spectrometry and one- and two-dimensional NMR spectroscopy. Primary assessment of the in vitro cytotoxic activity of 16 synthesized compounds against a panel of 60 tumor cell lines was performed. Results and Discussion: It was found that the introduction of a diethoxyphosphoryl substituent in the C1 position of the E ring of methyl dihydroquinopimarate and of a benzylamine fragment in the C20 position of maleopimaric acid resulted in the preparation of compounds that showed a pronounced cytotoxic activity. Conclusions: Diethoxyphosphoryl derivatives (XIX) and (XVII), and benzylamide (IX) were found to be cytotoxic against one, seven, and four breast cancer, leukemia, nonsmall cell lung cancer, and melanoma and prostate cancer cell lines, respectively. The highest activity was demonstrated by maleopimaric acid benzylamide (XIII), which effectively inhibited the growth of 19 cell lines of eight cancer types and had a significant cytotoxic effect against all the studied leukemia cell lines. The resulting data show that the synthesized derivatives can be recommended for in-depth study and development of a promising group of cytotoxic drugs. [ABSTRACT FROM AUTHOR]

A series of new diterpene quinopimaric acid derivatives modified at the hydroxyl group with different pharmacophore fragments has been synthesised and their (along with previously obtained compounds) inhibitory properties towards cholinesterases were studied. Thereby an indole-3-acetyl derivative 7 and a propargyl substituted compound 28 were shown to be excellent and acetylcholinesterase-selective inhibitors. Both compounds inhibited the enzyme as a mixed type inhibitor, and Ki values of 0.41 and 0.44 µM and Ki' values of 0.98 and 2.26 µM were determined. The binding interactions between all active compounds and ligands protein were confirmed through molecular docking study. [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]

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]

A new abietane diterpenoid, 1β, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2–4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [ABSTRACT FROM AUTHOR]

Six new abietane diterpenoids (1−6) and five undescribed iridoids (7−11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC 50 value of 7.83 ± 1.28 μmol·L−1. Additionally, compounds 1, 2, 4, 9 , and 10 manifested moderate cytotoxic effects on specific cell lines, with IC 50 values ranging from 11.7 to 20.9 μmol·L−1. [ABSTRACT FROM AUTHOR]

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.

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]

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]

• Column chromatography fractionation of the essential oil of Tetradenia riparia. • Isolation of the abietane diterpenoid 9β,13β-epoxy-7-abietene as reddish crystals. • First report on the crystalline structure of 9β,13β-epoxy-7-abietene. • DFT calculations support the proposed stereochemistry for 9β,13β-epoxy-7-abietene. In the pursuit of new botanical natural products with potential for the development of natural nematicides, the essential oil of Tetradenia riparia was chemically characterized by GC–MS and subjected to nematicidal activity tests. Two compounds identified as major components by GC–MS analysis could not be determined by comparing their mass spectra with library data. Fractionation of the oil by column chromatography allowed isolation of the compounds, identified as 9β,13β -epoxy-7-abietene and 6,7-dehydroroyleanone. Both compounds were obtained as suitable crystals for single-crystal X-ray diffraction analysis. This work facilitated the pioneering report of the crystal structure of the diterpenoid abietane 9β,13β -epoxy-7-abietene, previously reported as an amorphous solid. DFT calculations performed at the B3LYP-D3/Def2-SVP level provided insight into the relative stability and proposed stereochemistry of 9β,13β -epoxy-7-abietene. Finally, the essential oil did not exhibit significant activity in inhibiting egg hatching or causing mortality of the phytopathogenic nematode Meloidogyne incognita. [Display omitted] [ABSTRACT FROM AUTHOR]

Two new abietane diterpenoids ( 1 and 2 ) and two known analogs ( 3 and 4 ) were isolated from the whole plants of Phlegmariurus carinatus . Their structures were determined by comprehensive spectroscopic methods (UV, IR, NMR, and HRESIMS). Moreover, all compounds were evaluated for their cytotoxic activities against U251 glioblastoma cells. Notably, compounds 1-4 exhibited potential cytotoxic activities with IC 50 values ranging from 19.81 to 81.49 μM. In addition, their stabilities were checked by HPLC in the preservation conditions and in the cell lines medium. The result showed that they were relatively stable in the preservation conditions, except for 3 , but that they were decomposed in the incubation process. Finally, the most possible structures of impurities i1 , i3 and i4 were deduced by spectroscopic methods (UV, HRESIMS and MS/MS). This work provides potential insights for the development of abietane diterpenoids as candidate drugs for the treatment of glioma.

Eighteen aromatic abietane-type diterpenes, including three previously unreported compounds, Salkanoids A-C (1-3), were isolated from the roots of Salvia prattii. Their stuctures were extensively elucidated using 1D/2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS) data, and ECD calculation. Among these, compounds 1, 6 and 7 belong to a class of diterpenes featuring a [5, 5]-oxaspirolactones moiety, a rare structure isolated from the Salvia plants. All the isolates were assessed for their protective effects against alcoholic liver disease using ethanol-induced AML-12 cell lines. The findings revealed that compounds 2, 5, 8 and 15 demonstrated potential protective activity., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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]

The incidence of diabetes mellitus (DM), one of the most common chronic metabolic disorders, has increased dramatically over the past decade and has resulted in higher rates of morbidity and mortality worldwide. The enzyme, α-Glucosidase (α-GLy), is considered a therapeutic target for the treatment of type 2 DM. Herein, we synthesized arylidene, heterocyclic, cyanoetoxy- and propargylated derivatives of quinopimaric acid (levopimaric acid diene adduct with p-benzoquinone) 1–50 and, first, evaluated their ability to inhibit α-GLy. Among the tested compounds, quinopimaric acid 1, 2,3-dihydroquinopimaric acid 8 and its amide and heterocyclic derivatives 9, 30, 33, 39, 44, with IC50 values of 35.57–65.98 μM, emerged as being good inhibitors of α-GLy. Arylidene 1β-hydroxy and 1β,13α-epoxy methyl dihydroquinopimarate derivatives 6, 7, 26–29, thiadiazole 32, 1a,4a-dehydroquinopimaric acid 40 and its indole, nitrile and propargyl hybrids 35–38, 42, 45, 48, and 50 showed excellent inhibitory activities. The most active compounds 38, 45, 48, and 50 displayed IC50 values of 0.15 to 0.68 μM, being 1206 to 266 more active than acarbose (IC50 of 181.02 μM). Kinetic analysis revealed the most active diterpene indole with an alkyne substituent 45 as a competitive inhibitor with Ki of 50.45 μM. Molecular modeling supported this finding and suggested that the indole core plays a key role in the binding. Compound 45 also has favorable pharmacokinetic and safety properties, according to the computational ADMET profiling. The results suggested that quinopimaric acid derivatives should be considered as potential candidates for novel alternative therapies in the treatment of type 2 diabetes. [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 roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol (1), taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1H- and 13C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds. Salvia spinosa produces cytotxic abietane diterpenoids [ABSTRACT FROM AUTHOR]

The introduction of the alkynyl moiety to the abietane diterpenic core by modification of the cycle E of methyl dihydroquinopimarate is described. The arylpropargyl, aminopropargyl, and 1,2,3-triazole derivatives are synthesized via Sonogashira reaction, Mannich reaction and click-chemistry, correspondingly. The antitumor effect towards the NCI-60 cancer cell line panel and antimicrobial activity against key ESKAPE pathogens of the synthesized compounds were studied in vitro. The cytotoxicity and hemolytic activity of the abietane derivatives was tested using HEK293 human embryonic kidney cell line and the human red blood cells, correspondingly. The methyl dihydroquinopimarate propargyl analogs showed high antitumor activity against leukemia (CCRF-CEM; SR), non-small cell lung cancer (NCI-H522), melanoma (LOX IMVI; MALME-3M), ovarian cancer (IGROV1), and renal cancer (786-0; UO-31) cell lines. The Mannich's diterpene bases with pyrrolidine and diethylamine fragments exhibited fungicidal activity towards Cr. neoformans (MIC= 16 μg/ml), while possessing low toxicity. The described modifications of the abietane diterpenoids have great potential for further development of new cytotoxic and fungicidal compounds. [ABSTRACT FROM AUTHOR]

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]

Leucosceptrum canum Sm. , belonging to the Lamiaceae family, is a colorful, aromatic woody plant renowned for its nectar production. Extensive phytochemical research over the years has led to the identification of numerous chemical constituents within L. canum , particularly highlighting diterpenoids and sesterterpenoids as its characteristic compounds. L. canum has demonstrated a wide range of biological activities including antibacterial, cytotoxic, antifeedant, insecticidal, herbicidal, immunomodulatory and showed potential properties for treatment of heat stroke, anonymous swollen, impetigo, suppurative osteomyelitis, traumatic injury, and bleeding wound. Phytochemical investigation on L. canum exhibits chemophenetic significance based on its characteristic compounds. Additionally, sesterterpenoids and some other compounds serve as valuable chemotaxonomic marker of this genus, since there are no reports on their isolation from other genera and families. In the current article, the latest research progress on L. canum was reviewed to have a more comprehensive and systemic understanding of the plant. Further exploration of its pharmacological potential and elucidation of its chemical diversity could pave the way for novel applications and therapeutic interventions. [Display omitted] • Leucosceptrum canum Sm. (Lamiaceae) is a colored, fragrant, nectar woody plant. • Diterpenoids and sesterterpenoids are identified as the characteristic compounds. • L. canum is a potent insecticidal agent. • L. canum possesses antibacterial, cytotoxic, antifeedant, insecticidal, herbicidal, and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A–K (1 – 11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7 , 9 , 15 , and 16 showed significant inhibitory effects with IC 50 values ranging from 12.73 to 23.80 μM. The preliminary structure-activity relationship of these compounds was also discussed. [Display omitted] • Eleven previously undescribed abietane diterpenoids were isolated from C. incana. • The absolute configurations were elucidated by NMR and ECD calculations. • Four compounds displayed IC 50 values ranging from 12.73 to 23.80 μM against HIF-2α. [ABSTRACT FROM AUTHOR]

The new abietane diterpene indoles were synthesized by the Nenitzescu reaction of 1a,4a-dehydroquinopimaric acid and its methyl ester with methyl-3-aminocrotonate. [ABSTRACT FROM AUTHOR]

Purpose: Zhumeria majdae, a unique species of the Zhumeria genus, is an endemic Iranian plant in the Lamiaceae family. Phytochemical investigation and biological activity of this plant are rarely reported. The current study aimed to find new antiprotozoal compounds from the roots of Z. majdae and to determine the absolute configuration of isolated compounds by circular dichroism. Methods: The extraction process from roots and aerial parts of Z. majdae was carried out by hexane, ethyl acetate and methanol followed by testing their antiprotozoal effects against Leishmania donovani, Trypanosoma brucei rhodesiense, T. cruzi, and Plasmodium falciparum, respectively. Structure elucidation was done using 1D and 2D NMR spectroscopy and HREIMS spectrometry. In addition, experimental and theoretical circular dichroism spectroscopy was used to establish absolute configuration. Results: In comparison with aerial parts, the hexane extract from roots showed superior activity against T. b. rhodesiense, L. donovani and P. falciparum with IC50 values of 5.4, 1.6 and 2.1 μg/ml, respectively. From eight abietane-type diterpenoids identified in roots, six were reported for the first time in the genus Zhumeria. 11,14-dihydroxy-8,11,13-abietatrien-7-one (6) exhibited a promising biological activity against P. falciparum (IC50 8.65 μM), with a selectivity index (SI) of 4.6, and lanugon Q (8) showed an IC50 value of 0.13 μM and SI of 15.4 against T. b. rhodesiense. Conclusion: Altogether, according to the results, of 8 isolated compounds, dihydroxy-8,11,13-abietatrien-7-one (6) and lanugon Q (8) exhibited a promising activity against T. b. rhodesiense and P. falciparum. In conclusion, these compounds could be potential candidates for further analysis and may serve as lead compounds for the synthesis of antiprotozoal agents. [ABSTRACT FROM AUTHOR]

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1 – 6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α , β -unsaturated five-element ketone. All the compounds and four compounds (13 – 16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5 , 8 , 9 , 11 , and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 μM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of β -cyclodextrin ( β -CD)-conjugates were prepared by combining three abietane-type diterpene acids with two azide-functionalized β -CDs via click chemistry, and the antiviral activity against wild-type and omicron SARS-CoV-2 spike pseudovirus as well as the antibacterial activity against Escherichia coli were investigated. All the synthesised conjugates exhibited no significant cytotoxicity to BHK-21-hACE2 cells with cell viability over 80% at concentration of 15  µ M. Among the conjugates, the heptavalent β -CD-dehydroabietic acid conjugate 6b exhibited higher anti-SARS-CoV-2 activity against the omicron variant compared to the other conjugates. This study suggested that the multivalent diterpene acid derivatives may have potential application against coronaviruses as entry inhibitors.

Five new compounds (1, 2, 7, 12, and 16), along with fifteen known ones, were isolated from Ajuga lupulina Maxim. Their structures were revealed by analysing spectroscopic data (MS, NMR), and experimental and calculated ECD spectra was used to deduce the absolute configuration. Compound 16, with eight carbon atoms, was firstly isolated from the nature. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis in HT22 mouse hippocampal neuronal cells. Among them, the abietane-type diterpenoids (7-11) significantly inhibited ferroptosis with EC 50 values of 0.83 μM, 2.05 μM, 0.96 μM, 1.47 μM, and 1.19 μM, respectively., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Salvia corrugata Vahl. is an interesting source of abietane and abeo-abietane compounds that showed antibacterial, antitumor, and cytotoxic activities. The aim of the study was to obtain transformed roots of S. corrugata and to evaluate the production of terpenoids in comparison with in vivo root production. Hairy roots were initiated from leaf explants by infection with ATCC 15834 Agrobacterium rhizogenes onto hormone-free Murashige and Skoog (MS) solid medium. Transformation was confirmed by polymerase chain reaction analysis of rolC and virC1 genes. The biomass production was obtained in hormone-free liquid MS medium using Temporary Immersion System bioreactor RITA®. The chromatographic separation of the methanolic extract of the untransformed roots afforded horminone, ferruginol, 7-O-acetylhorminone and 7-O-methylhorminone. Agastol and ferruginol were isolated and quantified from the hairy roots. The amount of these metabolites indicated that the hairy roots of S. corrugata can be considered a source of these compounds.

Phytochemical investigation on the leaves of Rabdosia serra led to the isolation of two new abietane diterpenoids, raserranes A (1) and B (2), and four known phenylpropanoids (3–6). Their structures were determined by spectroscopic data. Compound 1 represented the rare examples of abietane diterpenoids featuring a 16-methoxycarbonyl group. [ABSTRACT FROM AUTHOR]

The funerary rites of particular members of the pre-Hispanic Mayan society included the pigmentation of the corpse with a red color. In order to understand this ritual, it is first necessary to identify the constituents of the pigment mixture and then, based on its properties, analyze the possible form and moment of application. In the present approach, 1H-NMR analysis was carried to detect organic components in the funerary pigments of Xcambó, a small Maya settlement in the Yucatan Peninsula. The comparison of the spectra belonging to the pigment found in the bone remains of seven individuals, and those from natural materials, led to the identification of beeswax and an abietane resin as constituents of the pigment, thus conferring it agglutinant and aromatic properties, respectively. The 1H-NMR analysis also allowed to rule out the presence of copal, a resin found in the pigment cover from paramount chiefs from the Mayan society. Additionally, a protocol for the extraction of the organic fraction from the bone segment without visible signs of analysis was developed, thus broadening the techniques available to investigate these valuable samples.

Plectranthus spp., commonly used in folk medicine, stands as a significant source of bioactive abietane diterpenoids with a broad spectrum of biological activities, supported by recent scientific studies. Herein, it is reported several approaches using these bioactive lead molecules obtained from Plectranthus spp. for therapeutics applications, such as Parvifloron D (ParvD) isolated from P. ecklonii, or 7a-acetoxy-6ß-hydroxyroyleanone (Roy) isolated from P. grandidentatus. A particular example is the patented diterpenoid benzoylroyleanone (RoyBz), prepared from natural Roy. RoyBz was identified as a PKC-selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKC-dependent mitochondrial apoptotic pathway. Notably, the PKCd-dependent anticancer activity was recapitulated in vivo using xenograft mouse models of control and PKCd-knockdown human colon cancer cells. We further investigate the molecular mechanism underlying the reported antitumor activity of Roy-Bz, and herein, we investigated the impact of Roy-Bz on glucose metabolism of colon cancer cells. This work provides insights into the role of PKC in tumor cell metabolism. Moreover, it strongly supports the ability of Roy-Bz to target both ATP producing pathways of glucose metabolism in cancer cells, thereby reinforcing its potential as an anticancer agent. [ABSTRACT FROM AUTHOR]

Medicinal plants of the Plectranthus genus (Lamiaceae) are well known for their ethnomedicinal applications. Plectranthus madagascariensis, which is native to South Africa, is traditionally used in the treatment of respiratory conditions, scabies, and cutaneous wounds. The phytochemical studies of P. madagascariensis led to the isolation of five known royleanone abietanes, namely, 6β,7α-dihydroxyroyleanone (1), 7α-acetoxy-6β-hydroxyroyleanone (2), horminone (3), coleon U quinone (4), and carnosolon (5). The relative configuration of compound 2 was established by X-ray analysis. Compounds 1–4 showed antimycobacterial activity (Minimum inhibitory concentration for 90% inhibition, MIC90 = 5.61–179.60 μM) against Mycobacterium tuberculosis H37Rv. Compound 4 and 5 showed comparable toxicity (Concentration for 50% inhibition, IC50 98.49 μM and 79.77 μM) to tamoxifen (IC50 22.00 μg/mL) against HaCaT cells. Compounds 1–5 showed antioxidant activity through single-electron transfer (SET) and/or hydrogen-atom transfer (HAT) with compound 5 being the most active antioxidant agent. Compounds 3 and 5 were isolated for the first time from P. madagascariensis. The observed results suggest P. madagascariensis as an important ethnomedicinal plant and as a promising source of diterpenoids with potential use in the treatment of tuberculosis and psoriasis.

Abstract Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known diterpenoid (3–6) were isolated from Salvia multicaulis. Structures were elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D-NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As several metabolites exhibited activity against drug-resistance lines, compounds were screened against a panel of human drug-sensitive and multidrug-resistant cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1 – 2) as well as the cytotoxic structure-activity relationship of all identified compounds were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC 50 11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000, respectively. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the root extracts of Salvia tebesana Bunge led to the isolation of two new diterpenoids, tebesinone A ( 1 ) and tebesinone B ( 2 ), along with two known compounds, aegyptinone A ( 3 ) and aegyptinone B ( 4 ). The structures were established by spectroscopic analysis including 1D and 2D NMR and HRESIMS. The cytotoxic activities of the crude extracts and isolated compounds were evaluated against MCF-7, B16F10, PC-3 and C26 human cancer cell lines, in which compounds 2 and 3 showed significant cytotoxic activities (IC 50 2.1–10.3 μM). [ABSTRACT FROM AUTHOR]

A new abietane diterpenoid, 12-O-methyl-20-deoxocarnosol-3-one (1), and eight known abietane diterpenoids including 13-abietadien-12-one (2), 5,6-dehydrosugiol (3), sugiol (4), torreyayunnin (5), taxusabietane A (6), hinokiol (7), 3-acetoxyabieta-8,11,13-trien-12-ol (8), and martiusane (9) were obtained from leaves and twigs of Cephalotaxus lanceolata. The structures of isolated compounds (1–9) were determined based on analysis of their spectroscopic data and comparison with those reported in the literature. Compounds 3, 8 and 9 were first isolated from the plants of Cephalotaxus genus. [ABSTRACT FROM AUTHOR]

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1-5) are reported for the first time. Their structures were established by spectroscopic means, mainly 1H- and 13C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC50 (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC50 (µM) = 0.0.46 ± 0.05 and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC50 (µM) = 0.08 ± 0.003 and 0.05 ± 0.003, as the positive control), respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC50 = 98. 4 ± 3.3), using α-tocopherol as the positive control (IC50 (µM) = 31.7 ± 1.04). The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae. [ABSTRACT FROM AUTHOR]

In searching for naturally occurring anti-inflammatory agents, three new abietane-type diterpenoids, named 16-hydroxylambertic acid ( 1 ), 7-oxo-18-hydroxyferruginol ( 2 ), and 5 α ,12-dihydroxy-6-oxa-abieta-8,11,13-trien-7-one ( 3 ), were isolated from the seeds of Podocarpus nagi , together with three known compounds. The structures of the new compounds were elucidated by extensive analysis of NMR and HR-ESIMS data. All the new compounds were tested for nitric oxide (NO) inhibitory activities on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Compound 1 significantly inhibited NO production with IC 50 value of 5.38 ± 0.17 μM, and suppressed inducible NO synthase (iNOS) expression in a dose-dependent manner, which were mediated through inhibiting the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation. [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.

Plectranthus barbatus is largely used in the Northeast region of Brazil by the local population for treatment of digestive problems as substitute of boldo (Pneumus boldus). Phytochemical analysis of the leaf extracts of Plectranthus barbatus (Labiatae) cultivated in this region yielded two abietane diterpenoids, cyclobubatusin (1) and barbatusin (2) and a new one named 7beta-acetyl-12-deacetoxycyclobutatusin (3). The structures of the isolated compounds were established by spectral analysis, using mainly mass spectra and ¹H and 13CNMR (1D and 2D). These procedures permitted the assignment of all chemical shifts in the diterpenoids.

Sahandinone (1), 12-deoxysalvipisone (2), miltirone (3), 7α-acetoxyroyleanone (4), and labda-7,14-dien-13-ol (5) were isolated from the roots of Salvia rhytidea Benth. (Lamiaceae). Their structures were elucidated by a combination of spectroscopic analyses including EIMS and NMR. The 13C NMR spectroscopic data were revised for the quaternary carbons of both 1 and 3 with the help of HMBC spectra in respect to the spectral data previously reported in the literature. Compounds 1 and 3, two very potent anticancer agents, were isolated in high yields from the roots of the plant. The biological activities of the plants' constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial are discussed in this article. The major anticancer agents from Salvia rhytidea. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the leaves of Callicarpa kwangtungensis led to the isolation of three new diterpenoids ( 1 – 3 ), callipenes A–C, and eleven known analogues ( 4 – 14 ). Their structures were established on the basis of extensive analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and calculated electronic circular dichroism spectra. Compounds 1 and 2 are rare abietane diterpenoids possessing a peroxide bridge. All of the isolates were found to inhibit LPS-induced NO production in BV-2 cells. [ABSTRACT FROM AUTHOR]

The increasing importance of multi-resistant strains and microbial biofilms in the development of chronic infections has driven the search for more effective alternative therapy including plant-origin preparations. The present study evaluates the broadly-defined antimicrobial activity of two abietane diterpenoids isolated from Salvia austriaca transformed roots: taxodone and 15-deoxy-fuerstione. The direct biostatic/biocidal effect of these phytocompounds and their influence on Staphylococcus aureus and Candida albicans virulence factors/mechanisms (adhesion, biofilm formation, agglutination in human plasma, survival in the blood, germ tube and mycelium formation) were tested using in vitro assays. Both phytocompounds significantly inhibited microbial adhesion and biofilm formation when used at ½ and ¼ MIC. Additionally, taxodone was able to limit staphylococcal survival in human blood, as well as C. albicans germ tube formation and hyphal growth. The tested diterpenoids express significant anti-biofilm activity against both staphylococci and yeast, and adversely affect their virulence factors/mechanisms, which are relevant in the course of the infection in vivo . Therefore, they demonstrate considerable biomedical potential as complements for classic therapy with antibiotics. [ABSTRACT FROM AUTHOR]

Five new abietane diterpenoids, named abifadines A–E ( 1 – 5 ), and nine known ones ( 6 – 14 ), together with two known podocarpenes ( 15 and 16 ), were isolated from the branch and leaf of Abies fargesii . Their structures including the relative configurations were established on the basis of extensive spectroscopic analyses. The absolute configuration of 1 was determined through single-crystal X-ray diffraction analysis with Cu K α irradiation. All the isolates were evaluated for their in vitro cytotoxicities. Only compounds 5 and 12 exhibited weak anti-proliferative effects against three cancer cell lines (B16, MCF7, and HepG2) with IC 50 values range from 14.8 to 42.8 μM. The antimicrobial activities against Staphylococcus aureus, Escherichia coli and Monilia albicans of all compounds were also tested, but none of them showed significant activities. [ABSTRACT FROM AUTHOR]

This review presents the phytochemical constituents of the genus Plectranthus reported up to 1999. Only a tetrameric derivative of caffeic acid was isolated from P. japonicus, but a group of long-chain alkylphenols, of possible taxonomic significance in the genus, was also isolated. As a genus of the subfamily Nepetoideae, Plectranthus is free from iridoid glycosides and rich in essential oil (i.e. > 0.5% volatile oil on a dry weight basis). Diterpenoids are the more common secondary metabolites in Plectranthus. The majority of them are highly modified abietanoids. This seems to be similar to the pattern of diterpenoids observed for Salvia, but no clerodane diterpenoids were found in Plectranthus.

Four new aromatic abietane diterpenoids and two new benzene derivatives, namely perenacidins A–F ( 1 – 6 ), have been isolated from the fruiting bodies of Basidiomycete Perenniporia subacida . The structures were elucidated by means of extensive spectroscopic methods and computational ECD method. The antifungal activities against Canidia albicans and the cytotoxic activities against four cancer cell lines (including K-562, A-549, SMMC-7721, MCF-7) were evaluated in vitro . [ABSTRACT FROM AUTHOR]