C19-diterpene alkaloids from Delphinium turkmenum lipsky.

The genus Delphinium is a rich source of diterpene alkaloids. Chemical investigation on an alkaloid rich extract of the whole parts of Delphinium turkmenum resulted in the isolation of three C19-diterpene alkaloids (1-3) and a palmitic acid derivative (4). The chemical structures were elucidated by analysis of 1D and 2D-NMR and comparison the data with those reported in the literature. Notably, all isolated compounds were reported for the first time from D. turkmenum.

Diverse diterpenoids and a triterpenoid from Euphorbia spinidens Bornm. ex Prokh.

Four previously unreported diterpenoids including three ent-atisanes (1-3) and one ent-abietane (4), along with one known linear triterpenoid (5) and five known diterpenoids including four myrsinanes (6-9), and one abietane (10) have been isolated from the roots of Euphorbia spinidens Bornm. ex Prokh. The structures were determined on the basis of extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR and comparison of the data with those reported in the literature. Antimicrobial potential of isolated compounds were also evaluated. Guionianol B (10) showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis with MIC value of 6.25 µg/mL.

Indonesian Euphorbiaceae: Ethnobotanical Survey, In Vitro Antibacterial, Antitumour Screening and Phytochemical Analysis of Euphorbia atoto.

Indonesia is among the countries with the most significant biodiversity globally. Jamu, the traditional medicine of Indonesia, predominantly uses herbal materials and is an integral component of the Indonesian healthcare system. The present study reviewed the ethnobotanical data of seven Indonesian Euphorbiaceae species, namely Euphorbia atoto, E. hypericifolia, Homalanthus giganteus, Macaranga tanarius, Mallotus mollissimus, M. rufidulus, and Shirakiopsis indica, based on the RISTOJA database and other literature sources. An antimicrobial screening of the plant extracts was performed in 15 microorganisms using the disk diffusion and broth microdilution methods, and the antiproliferative effects were examined in drug-sensitive Colo 205 and resistant Colo 320 cells by the MTT assay. The antimicrobial testing showed a high potency of M. tanarius, H. giganteus, M. rufidulus, S. indica, and E. atoto extracts (MIC = 12.5-500 µg/mL) against different bacteria. In the antitumour screening, remarkable activities (IC50 0.23-2.60 µg/mL) were demonstrated for the extracts of H. giganteus, M. rufidulus, S. indica, and E. atoto against Colo 205 cells. The n-hexane extract of E. atoto, with an IC50 value of 0.24 ± 0.06 µg/mL (Colo 205), was subjected to multistep chromatographic separation, and 24-methylene-cycloartan-3ß-ol, jolkinolide E, tetra-tert-butyl-diphenyl ether, α-tocopherol, and ß-sitosterol were isolated.

Furanonaphthoquinones, Diterpenes, and Flavonoids from Sweet Marjoram and Investigation of Antimicrobial, Bacterial Efflux, and Biofilm Formation Inhibitory Activities.

The chloroform extract of Origanum majorana exhibited high antibacterial and antifungal activities against 12 bacterial and 4 fungal strains; therefore, it was subjected to bioassay-guided isolation to afford six compounds (1-6). The structures were determined via one- and two-dimensional nuclear magnetic spectroscopy and high-resolution electrospray ionization mass spectrometry experiments. The compounds were identified as furanonaphthoquinones [majoranaquinone (1), 2,3-dimethylnaphtho[2,3-b]furan-4,9-dione (2)], diterpenes [19-hydroxyabieta-8,11,13-trien-7-one (3), 13,14-seco-13-oxo-19-hydroxyabieta-8-en-14-al (4)], and flavonoids [sterubin (5) and majoranin (6)]. Compounds 1 and 2 were first obtained from a natural source and compounds 3 and 4 were previously undescribed. Majoranaquinone (1) exhibited a high antibacterial effect against 4 Staphylococcus, 1 Moraxella, and 1 Enterococcus strains (MIC values between 7.8 µM and 1 mM). In the efflux pump inhibition assay, majoranaquinone (1) showed substantial activity in Escherichia coli ATCC 25922 strain. Furthermore, 1 was found to be an effective biofilm formation inhibitor on E. coli ATCC 25922 and E. coli K-12 AG100 bacteria. Our findings proved that bioactivities of majoranaquinone (1) significantly exceed those of the essential oil constituents; therefore, it should also be considered when assessing the antimicrobial effects of O. majorana.

Anticancer Meroterpenoids from Centrapalus pauciflorus leaves: Chromone- and 2,4-Chromadione-Monoterpene Derivatives.

Eight previously undescribed chromones, named pauciflorins F-M and two 5-methyl-2,4-chromadione derivatives named as pauciflorins N and O, were isolated from the methanol extract of the leaves of Centrapalus pauciflorus (Willd.) H.Rob. together with the known (+)-spiro-ethuliacoumarin. The structures were determined via extensive spectroscopic analyses, including HRESIMS, 1D NMR (1H, 13C JMOD), and 2D NMR (HSQC, HMBC, 1H-1H COSY, and NOESY) experiments. Through an MTT assay, seven isolated compounds were tested for their antiproliferative properties against human adherent breast (MCF-7, MDA-MB-231), cervical (HeLa, SiHa), and ovarian (A2780) cancer cell lines. Pauciflorin F was effective against MCF-7 breast cancer cells, its activity (IC50 5.78 µM) was comparable to that of the reference agent cisplatin (IC50 5.78 µM).

Isolation of compounds from the roots of Ambrosia artemisiifolia and their effects on human cancer cell lines.

Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe with spreading use in the contemporary folk medicine. The chemical composition of the above-ground parts is extensively studied, however, the metabolites of the roots are less discovered. By multiple chromatographic purification of the root extracts, we isolated thiophene A (1), n-dodecene (2), taraxerol-3-O-acetate (3), α-linoleic acid (4), (+)-pinoresinol (5), and thiophene E (7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol) (6). The 1H NMR data published earlier for 1 were supplemented together with the assignment of 13C NMR data. Thiophene E (6), which is reported for the first time from this species, exerted cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells, whereas taraxerol-3-O-acetate (3) and α-linoleic acid (4) had slight antiproliferative effect on gynecological cancer cell lines. Thiophene E (6) and taraxerol-3-O-acetate (3) displayed antiproliferative and cytotoxic effects on MRC-5 fibroblast cells. Thiophene E (6) exerted weak antibacterial activity (MIC 25 µg/mL) on MRSA ATCC 43300, on Staphylococcus aureus ATCC 25923, Escherichia coli AG100 and E. coli ATCC 25922 both thiophenes were inactive. Although the isolated compounds exerted no remarkable cytotoxic or antiproliferative activities, the effects on MRC-5 fibroblast cells highlight the necessity of further studies to support the safety of ragweed root.

An overview of the traditional use, phytochemistry, and biological activity of the genus Homalanthus.

Homalanthus species are native to tropical Asia and the Pacific region. This genus, comprising 23 accepted species, received less scientific attention compared to other genera of the Euphorbiaceae family. Seven Homalanthus species, such as H. giganteus, H. macradenius, H. nutans, H. nervosus, N. novoguineensis, H. populneus, and H. populifolius, have been reported to treat various health problems in traditional medicine. Only a few Homalanthus species have been investigated for their biological activities, including antibacterial, anti-HIV, anti-protozoal, estrogenic, and wound-healing activities. From a phytochemical point of view ent-atisane, ent-kaurane, and tigliane diterpenoids, triterpenoids, coumarins, and flavonol glycosides were found to be characteristic metabolites of the genus. The most promising compound is prostratin, isolated from H. nutans, with anti-HIV activity and the ability to eradicate the HIV reservoir in infected patients by mechanism of protein kinase C (PKC) agonist. This review provides information on traditional usage, phytochemistry, and biological activity of the genus Homalanthus with the aim to delineate future research directions.

Pauciflorins A-E, Unexpected Chromone-Monoterpene-Derived Meroterpenoids from Centrapalus pauciflorus.

Five unusual meroterpenoids based on new carbon skeletons, pauciflorins A-E (1-5), were isolated by multistep chromatographic separations of a methanol extract of the aerial parts of Centrapalus pauciflorus. Compounds 1-3 are derived by the connection of a 2-nor-chromone and a monoterpene unit, whereas 4 and 5 are dihydrochromone-monoterpene adducts with a rarely occurring orthoester functionality. The structures were solved using 1D and 2D NMR, HRESIMS, and single-crystal X-ray diffraction. Pauciflorins A-E were evaluated for antiproliferative activity against human gynecological cancer cell lines, but were inactive (IC50 < 10 µM) in each case.

Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata.

A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells.

Isolation of the Lanostane Triterpenes Pholiols L-S from Pholiota populnea and Evaluation of Their Antiproliferative and Cytotoxic Activities.

Pholiols L-S (1−8), eight undescribed triterpenes were isolated from the sporocarps of the mushroom Pholiota populnea. Various chromatographic techniques, such as open column chromatography, flash chromatography, gel filtration, preparative thin layer chromatography, and HPLC, were applied to purify the compounds. The structure elucidation was carried out by spectroscopic analysis, including 1D (1H NMR and 13C JMOD) and 2D NMR (1H-1H COSY, HSQC, HMBC and NOESY) and HRESIMS experiments. The isolated compounds had lanostane (1−7) or trinorlanostane (8) skeletons; all of them were substituted with 3-hydroxy-3-methylglutaroyl group or its 6-methyl ester. Five compounds (1, 2, 4, 6, and 8) were investigated for their antiproliferative and cytotoxic activity in vitro by MTT assay on breast cancer (MCF-7), human colon adenocarcinoma (sensitive Colo 205, and resistant Colo 320), non-small cell lung cancer (A549), and human embryonic lung fibroblast (MRC-5) cell lines. Pholiols M (2) and O (4) showed antiproliferative activity against the MCF-7 cell line with IC50 of 2.48 and 9.95 µM, respectively. These compounds displayed tumor cell selectivity on MCF-7 cells with SI values of >40 (2) and 4.3 (4), but they did not show a cytotoxic effect, proving their action exclusively on tumor cell proliferation. Pholiols L (1) and Q (8) were found to have selective cytotoxicity on drug resistant cells in comparison to their effects on Colo320 and Colo205 cells [relative resistance values 0.84 (1) and 0.62 (8)].

Pholiols E-K, lanostane-type triterpenes from Pholiota populnea with anti-inflammatory properties.

Investigation of the chloroform and ethyl acetate extracts of the edible mushroom Pholiota populnea led to the isolation of eight triterpenes, the undescribed natural products pholiols E-K and the known (+)-clavaric acid. HRESIMS and 1D and 2D NMR spectroscopy were employed to determine the structures of the undescribed compounds. The NOESY spectra were used to assign the relative configurations of triterpenes. The isolated compounds were screened for their anti-inflammatory activity on cyclooxygenase (COX-1 and COX-2), and lipoxygenase (5-LOX and 15-LOX) inhibitory assays. Dose-response investigations revealed that lanostane derivatives exhibited moderate 5-LOX and COX-2 inhibitory activities, with pholiol F (IC50 194.5 µM against 5-LOX and 439.8 µM against COX-2) the most active among the isolated compounds. Our findings indicated that P. populnea is an abundant source of new bioactive lanostane-type triterpenes.

Secondary metabolites from Gentiana cruciata L. and their anti-inflammatory and analgesic activities.

A previously unreported secoiridoid glycoside, cruciatoside (1) was isolated from the aerial parts of Gentiana cruciata L. along with ten known compounds eustomoside (2), eustomorusside (3), gentiopicroside (4), 6'-O-ß-D-glucopyranosyl gentiopicroside (5), loganic acid (6), isoorientin (7), isovitexin (8), isovitexin 2''-(E)-ferulate (9), mangiferin (10), and 2-methyl-inositol (11). The chemical structures of the isolates were elucidated based on extensive 1 D and 2 D NMR experiments as well as HRMS analysis. All isolates were evaluated for their in vitro anti-inflammatory and analgesic activities. Compounds 9, 4, and 7 (200 µM) showed moderate anti-inflammatory activity by inhibiting nitrite production from LPS-induced RAW 264.7 macrophage cells, with the inhibition rates of 39.5%, 25.8% and 22.9% respectively without exhibiting substantial cytotoxicity. Besides, 1, 2, 4, and 7 exerted the highest decrease in IL-6 levels. Moreover, compound 4 showed in vitro analgesic activity by decreasing the PGE2 level comparable to the reference drugs.

Ingol, ent-atisane, and stachane-type diterpenoids from Euphorbia deightonii with multidrug resistance reversing activity.

Nine previously undescribed ingol-type diterpenoid polyesters with eighteen known ingol esters, two ent-atisane, and one stachane diterpenoid were isolated from the methanol extract of Euphorbia deightonii Croizat. The structures were established by extensive spectroscopic analysis involving 1D (1H, 13C J-modulation) and 2D NMR experiments, HRESIMS measurements, and the comparison of the spectroscopic data with reported literature values. The cytotoxic concentrations of 13 isolated compounds were determined, and the compounds were investigated for multidrug resistance modulating activity on an L5178 mouse lymphoma cell line using a rhodamin 123 accumulation assay. Six ingol esters demonstrated the significant inhibition of P-glycoprotein, while the two ent-atisane diterpenoids were found to be inactive. The measured activities allowed to establish some structure-activity relationships. Notably, lower and higher-type diterpenoids simultaneously occurred in E. deightonii.

Cytotoxicity, apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells.

Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast adenocarcinoma (MCF-7 and MDA-MB-231) and prostate (PC3) cell lines. The methanolic extract exhibited the highest activity, and was chosen for the isolation procedure. Four diterpenoid quinones, namely miltirone [1], tanshinone IIA [2], 1-hydroxy-tanshinone IIA [3], and cryptotanshinone [4] were isolated. Notably, this is the first report on the isolation and/or characterization of the mentioned diterpenoids from the Stachys genus. In this study, 1-hydroxy-tanshinone IIA [3] displayed the highest cytotoxicity among the isolated compounds. The mechanism of the cytotoxicity of methanolic extract and isolated compounds was further investigated by the utilization of propidium iodide staining (PI) assay. The results showed that the methanolic extract and 1-hydroxy-tanshinone IIA [3] enhanced DNA fragmentation in PC3 and MCF-7 cells. Moreover, the western blotting analysis demonstrated increasing and decreasing protein levels of Bax and Bcl2, respectively, and cleaved poly ADP-ribose polymerase (PARP). Further bioassay-guided phytochemical assessments of S. parviflora can be suggested as a promising approach for discovering potent bioactive secondary metabolites.

A comprehensive phytochemical and pharmacological review on sesquiterpenes from the genus Ambrosia.

Sesquiterpenes are bitter secondary metabolites characteristic to the genus Ambrosia (Asteraceae) and constitute one of the most diverse classes of terpenoids. These compounds exhibit broad-spectrum bioactivities, such as antiproliferative, cytotoxic, antimicrobial, anti-inflammatory, molluscicidal, schistomicidal, larvicidal, and antiprotozoal activities. This review compiles and discusses the chemistry and pharmacology of sesquiterpenes of the Ambrosia species covering the period between 1950 and 2021. The review identified 158 sesquiterpenes previously isolated from 23 different Ambrosia species collected from across the American, African, and Asian continents. These compounds have guaiane, pseudoguaiane, seco-pseudoguaiane, daucane, germacrane, eudesmane, oplopane, clavane, and aromadendrane carbon skeletons. Most sesquiterpene compounds predominantly harbor the pseudoguaiane skeleton, whereas the eudesmanes have the most varied substituents. Antiproliferative and antiprotozoal activities are the most promising bioactivities of sesquiterpenes in Ambrosia and could lead to new pathways toward drug discovery.

Antimicrobial, Multidrug Resistance Reversal and Biofilm Formation Inhibitory Effect of Origanum majorana Extracts, Essential Oil and Monoterpenes.

Origanum majorana L. is a widely used medicinal plant; its distilled oil and preparations are extensively utilised in the phytotherapy and food industries. The objective of this study is to evaluate the extracts and the essential oil (EO) of Origanum majorana L, and its monoterpenes for antimicrobial, bacterial multidrug resistance reversing, and biofilm formation inhibitory potency. The composition of EO and n-hexane extract was characterized by GC-MS. In the essential oil terpinen-4-ol (24.92%), trans-sabinene hydrate (25.18%), γ-terpinene (6.48%), cis-sabinene hydrate (5.44%), p-cymene (4.72%), sabinene (4.53%), α-terpineol (4.43%), and α-terpinene (3.00%) were found as the main constituents while trans-sabinene hydrate (1.43%), and terpinen-4-ol (0.19%) were detected in the n-hexane extract besides a series of hydrocarbons. The antibacterial activity of EO and terpinen-4-ol, α-terpinene, and linalool was also assessed against sensitive and drug-resistant S. aureus, and E. coli strains with MIC values of 0.125-0.250% and 30-61 µM, respectively. In the efflux pump (EP) inhibitory assay, made by the ethidium bromide accumulation method in E. coli ATCC 25922, and AG100 and S. aureus ATCC 25923, and MRSA ATCC 43300 strains, EO exhibited substantial activity, especially in the E. coli ATCC 25922 strain. Among the EO constituents, only sabinene was an EP inhibitor in sensitive Escherichia strain. In the case of S. aureus strains, EO and sabinene hydrate exhibited moderate potency on the drug-resistant phenotype. The antibiofilm effects of the samples were tested by crystal violet staining at sub-MIC concentration. γ-Terpinene, terpinen-4-ol, sabinene, sabinene hydrate and linalool were found to be effective inhibitors of biofilm formation (inhibition 36-86%) on E. coli ATCC 25922 and S. aureus MRSA ATCC 43300, while EO was ineffective on these strains. In contrast to this, biofilms formed by E. coli AG100 and S. aureus ATCC 25923 were significantly inhibited by the EO; however, it was not affected by any of the monoterpenes. This observation suggests that the antibiofilm effect might be altered by the synergism between the components of the essential oil.

Polyoxypregnane Ester Derivatives and Lignans from Euphorbia gossypina var. coccinea Pax.

From the aerial parts of Euphorbiagossypina var. coccinea Pax., eight new pregnane glycosides (euphogossypins A-H, 1-8) of the cynanforidine and deacetylmetaplexigenin aglycons, two new lignans (gossypilignans A and B, 9 and 10), and four known compounds, namely, the pregnane 12-O-benzoyldeaxcylmetaplexigenin (11), the lignan 9α-hydroxypinoresinol (12), and the flavonoids naringenin (13) and quercitrin (14) were isolated. The structure elucidation of the new compounds was carried out by a spectroscopic analysis, including HRMS, 1D (1H, 13C JMOD), and 2D NMR (HSQC, 1H-1H COSY, HMBC, and NOESY) experiments. The obtained pregnane glycosides were substituted with acetyl and benzoyl ester moieties, and sugar chains containing thevetose, cymarose, digitoxose, and glucose monosaccharides. All of the compounds are described for the first time from E. gossypina var. coccinea. The isolated pregnanes and lignans were tested for their antiproliferative activity on HeLa cells using the MTT assay; the compounds exerted no significant effect against the tumor cells.

Triterpenes and Phenolic Compounds from Euphorbia deightonii with Antiviral Activity against Herpes Simplex Virus Type-2.

Two undescribed compounds, 3ß,7ß-dihydroxy-24-methylenelanosta-8-ene-11-one (1) and neolignane deightonin (4) were isolated from the aerial parts of Euphorbia deightonii Croizat together with six known compounds, namely, kansenone (2), euphorbol-7-one (3), dehydrodiconiferyl diacetate (5), marylaurencinol D (6), scoparon (7), and 3,4,3'-tri-O-methylellagic acid (8). The structures of the isolated compounds were determined by HRESIMS, 1D (1H, 13C JMOD) and 2D NMR (HSQC, HMBC, 1H-1H COSY, NOESY) spectroscopic analysis, and by comparison of the assignments with literature data. The anti-herpes simplex virus type-2 activity of the isolated compounds were investigated by qRT-PCR assay on Vero cells after determining cytotoxic concentration 50% (CC50). Compounds 1, 3, 4, and 7 exhibited inhibitory effects with respective IC50 values of 7.05, 2.42, 11.73, and 0.032 µM. Scoparon (7) showed the strongest anti-HSV activity with a selectivity index of 10.93.

Jacaranone Derivatives with Antiproliferative Activity from Crepis pulchra and Relevance of This Group of Plant Metabolites.

Jacaranones are a small group of specific plant metabolites with promising biological activities. The occurrence of jacaranones is limited to only a few plant families, with Asteraceae being the most abundant source of these compounds. Therefore, jacaranones can also serve as chemotaxonomic markers. Our phytochemical investigation of Crepis pulchra L. (Asteraceae) resulted in three jacaranone derivatives (jacaranone, 2,3-dihydro-2-hydroxyjacaranone, 2,3-dihydro-2-methoxyjacaranone), and (6R,9S)-3-oxo-α-ionol-ß-d-glucopyranoside, fulgidic acid, 12,15-octadecadienoic acid methyl ester, scopoletin and apigenin-7-O-ß-d-glucoside. This is the first report on the isolation of jacaranones from a species belonging to the Cichorioideae subfamily of Asteraceae. Jacaranone derivatives were subjected to an in vitro antiproliferative assay against a panel of human cancer cell lines (MCF-7, MDA-MB-231, HeLa, and C33A), revealing high or moderate activities, with IC50 values ranging from 6.3 to 26.5 µM.