Triterpenes from the roots of Lantana montevidensis with antiprotozoal activity

Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13β-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12β,13β-dihydroxyolean-3-oxo-28-oic acid (2) and 12β,13β,22β-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3β,25β-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19α-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with β-sitosterol (11) and β-sitosterol-3-O-β-d-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC₅₀ values against both organisms of 2.1 μM and compound 10 showed activity against same organisms with IC₅₀ values 8.74 and 8.09 μM, respectively, compared to the positive control ciprofloxacin (IC₅₀ = 0.3 μM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC₅₀ values ranging between (2.54–14.95 μM) and IC₉₀ values ranging between (11.90–19.47 μM), using pentamidine as a control (IC₅₀ values 2.09 ≥ 16.8 μM) and IC₉₀ values ranging between (4.72 ≥ 16.8 μM). These compounds also showed highly potent antitrypanosomal activity with IC₅₀ values ranging between (0.39–7.12 μM) and IC₉₀ values ranging between (1.91–10.51 μM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC₅₀ and IC₉₀values 11.82 and 30.82 μM).     

Aethusifolins A–D: Four new components from a traditional Mongolian medicinal herb Clematis aethusifolia Turcz

Four new components named aethusifolins A–D (1–4), together with ten known (5–14) were isolated from the dried aerial parts of a traditional Mongolian medicinal herb Clematis aethusifolia Turcz. The planar structures were established based on extensive spectroscopic analysis (HRMS, 1D and 2D NMR), and the absolute configurations were determined by modified Mosher’s method, hydrolysis method. The cytotoxicities of isolated compounds against a panel of five human solid tumor cell lines were assayed. Compounds 5, 8, and 13 showed moderate cytotoxicity against A-375 with IC₅₀ values of 15–18 μM, while compound 8 also showed cytotoxicity against SH-SY5Y with IC₅₀ values of 20 μM.     

Acridone alkaloids from Vepris verdoorniana (Excell & Mendonça) Mziray (Rutaceae)

Two new acridone alkaloids, verdoocridone A (1) and B (4), together with fifteen known compounds were isolated from methanol extracts of the roots and leaves of Vepris verdoorniana. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI- and ESI–MS). The ¹³C NMR values of 1,2,3,5-tetramethoxy-N-methylacridone (2) and 5-methoxyaborinine (3) are also reported. The crude extracts and compounds (1-6) were tested for their antimicrobial activity. The test delivered moderate activities for crude extracts and compounds 1, 5 and 6 against the bacterium Staphylococcus aureus and the fungi Mucor meihei and Candida albicans with MIC values between 115 and 180 μg/mL for extracts and between 21.3 and 29.4 μM for compounds, compared to gentamycin with 0.2 μM and nystatin with 5.2 μM against both fungi. The determination of the radical scanvenging activity using 1,1-dephenyl-2-picrylhydrazyl (DPPH) assay gave moderate antioxidant values for all tested compounds, with IC₅₀ between 0.29 and 0.41 μM, compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) displaying 0.03 μM.     

Chemical constituents of Ligularia alticola Worosch. leaves and their biological activities

Seven eremophilane-type sesquiterpenes (1–7), six cycloartane derivatives (8–13) and α-amyrin acetate (14) were isolated from the leaves of the far-eastern plant Ligularia alticola Worosch. (Family Asteraceae). (4S,5R,8S,10R)-8-Ethoxyeremophil-7(11)-en-12(8)-olide (1), 8α,11-epidioxy-8β-methoxyeremophil-6-ene (2) and 29-norcycloartan-3α-ol (8) have not been previously reported. Fukinone α-epoxide (3) was isolated for the first time from a natural source. The structures of all the compounds were established by the extensive analysis of their 1D and 2D NMR spectra and HR ESI mass spectrometry. The absolute stereochemistry of 1 was determined by comparison of theoretical and experimental ECD spectra with the application of B3LYP-TDDFT and B3LYP-GIAO calculations as well as by NMR spectroscopy. Compound 1 showed cytotoxic action against human cancer HL-60, Raji, and THP-1 cell lines (IC₅₀ 12.6, 6.0 and 6.9 μM, respectively). Compounds 2 and 4 demonstrated significant cytotoxic activities against HL-60 (IC₅₀ 2.8 and 5.8 μM, respectively) and Raji cells (IC₅₀ 2.9 and 4.2 μM, respectively). Compound 6 was cytotoxic against Raji cells (IC₅₀ 4.6 μM). None of tested compounds were cytotoxic against RAW 264.7 cells. Compounds 1 and 4–7 significantly decreased intracellular ROS levels, induced by endotoxic LPS from Escherichia coli in RAW 264.7 murine macrophages.     

Tirucallane triterpenoids from the stem bark of Araliopsis synopsis

Two new tirucallane triterpenoids, 21-methoxy-21,23-epoxy-tirucalla-7,24-dien-3α-ol (1) and 21-methoxy-21,23-epoxy-tirucalla-7,24-diene-1α,3α-diol (2), together with thirteen known compounds were isolated from the CH₂Cl₂ extract of the stem bark of Araliopsis synopsis. The structures of the compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data and comparison with previously known analogs. Compounds 1–10 were tested against bacteria, fungi and plant pathogen oomycetes by the paper disk agar diffusion assay resulting in missing to low activities corresponding with MICs > 1 mg/mL. However, compounds 5–10 exhibited high cytotoxic activity against the human Caucasian prostate adenocarcinoma cell PC-3 line, with IC₅₀ 8.5–12.5 μM compared to the standard Doxorubicin with IC₅₀ = 0.9 μM, while compounds 1, 3 and 4 showed low activity.     

Two new lignans from Gymnotheca chinensis Decne

Two new lignans, gymnothelignans V (1) and W (2), were isolated from a methanol extraction of Gymnotheca chinensis Decne. Their structures were established on the basis of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited moderate cytotoxicity against the HCT116, HCT15, A549, MCF-7 and HepG2 cancer cell lines with IC₅₀ values of 45.1 μM, 26.9 μM, 49.6 μM, 30.0 μM and 49.7 μM, respectively. Compound 2 exhibited weak cytotoxicity against the A549 cancer cell line with an IC₅₀ value of 41.3 μM.     

A new megastigmane from Kalanchoe tubiflora (Harvey) Hamet

One new megastigmane, (6S,7R,8R,9S)-6-oxaspiro-7,8-dihydroxymegastigman-4-en-3-one (1) (tubiflorone, 1), and ten known compounds were isolated and characterized from the EtOH extract of Kalanchoe tubiflora (Harvey) Hamet. Structures of these isolates were assigned based on spectroscopic analyses that included 1D and 2D NMR techniques, such as HMQC, HMBC, and NOESY. The anti-inflammatory activities of selected isolated compounds (1–6 and 9–11) were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Compounds 1–4, 6, 9, and 11 possessed nitric oxide inhibitory activity with IC₅₀ values ranging from 15.1 ± 0.9 to 98.9 ± 1.3 μM.     

Prenylated chalcones from Desmodium renifolium

Three new prenylated chalcones, renifolins A–C (1–3), together with seven known ones (4–10), were isolated from whole Desmodium renifolium plants. All of their structures were determined by spectroscopic methods including 1D and 2D NMR. Compounds 1 and 2 are the first naturally occurring chalcones possessing a 4-methylfuran-2(5H)-one unit. All of the isolates were evaluated for cytotoxicity using five tumor cell lines. Compounds 3–8, and 10 exhibited moderate cytotoxicity against certain cell lines with IC₅₀ values from 4.2 to 8.8 μM.     

Bioactive compounds from Stuhlmannia moavi from the Madagascar dry forest

Bioassay-directed fractionation of the leaf and root extracts of the antiproliferative Madagascar plant Stuhlmannia moavi afforded 6-acetyl-5,8-dihydroxy-2-methoxy-7-methyl-1,4-naphthoquinone (stuhlmoavin, 1) as the most active compound, with an IC₅₀ value of 8.1 μM against the A2780 human ovarian cancer cell line, as well as the known homoisoflavonoid bonducellin (2) and the stilbenoids 3,4,5′-trihydroxy-3′-methoxy-trans-stilbene (3), piceatannol (4), resveratrol (5), rhapontigenin (6), and isorhapontigenin (7). The structure elucidation of all compounds was based on NMR and mass spectroscopic data, and the structure of 1 was confirmed by a single crystal X-ray analysis. Compounds 2?5 showed weak A2780 activities, with IC₅₀ values of 10.6, 54.0, 41.0, and 74.0 μM, respectively. Compounds 1?3 also showed weak antimalarial activity against Plasmodium falciparum with IC₅₀ values of 23, 26, and 27 μM, respectively.     

Cytotoxic triterpenes with diverse skeletons from Amoora tsangii

Two new 29-nor-cycloartane triterpenes, amooratsanols A and B (1, 2) along with nine known compounds including two 29-nor-cycloartane triterpenes (3, 9), two lupane triterpenes (4, 5), two cycloartane triterpenes (6, 10), two dammarane triterpenes (7, 8), as well as one dinorcycloartane triterpene (11) were isolated from the leaves and twigs of Amoora tsangii (Merr.) X. M. Their structures were established by spectroscopic methods (IR, HRESIMS, and NMR). The cytotoxicity of 1–11 was evaluated against the human fibro sarcoma HT1080, esophageal cancer TE, and non-small cell lung cancer A549 cell lines by the CCK8 assay. Cycloartanes (1–3, 6, and 9–11) displayed significant cytotoxic activity with IC₅₀ values ranging from 2.56 to 19.05 μM. Among these triterpenes, mooratsanol A (1) showed the most potent cytotoxic activity, with IC₅₀ values ranging from 2.56 to 5.10 μM.     

Tyrosinase inhibitory effects of 1,3-diphenylpropanes from Broussonetia kazinoki

Six 1,3-diphenylpropanes exhibiting inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase were isolated from the methanol (95%) extract of Broussonetia kazinoki. These compounds, 1–6, were identified as kazinol C (1), D (2), F (3), broussonin C (4), kazinol S (5) and kazinol T (6). The latter two species (5 and 6) emerged to be new 1,3-diphenylpropanes which we fully spectroscopically characterized. The IC₅₀ values of compounds (1, 3–5) for monophenolase inhibition were determined to range between 0.43 and 17.9 μM. Compounds 1 and 3–5 also inhibited diphenolase significantly with IC₅₀ values of 22.8, 1.7, 0.57, and 26.9 μM, respectively. All four active tyrosinase inhibitors (1, 3–5) were competitive inhibitors. Interestigly they all mainfested simple reversible slow-binding inhibition against diphenolase. The most potent inhibitor, compound 4 diplayed the following kinetic parameters k₃ = 0.0993 μM^?1 min^?1, k₄ = 0.0048 min^-1, and K_i^app = 0.0485 μM.     

Acylated iridoid glycosides and acylated rhamnopyranoses from Gmelina arborea flowers

Nine acylated iridoid glycosides (1–9), five acylated rhamnopyranoses (10–14) and verbascoside (15) were isolated from Gmelina arborea flowers, including 5 new compounds (1, 2, and 10–12). The cytoprotective activity of 11 selected compounds (1–8, 10, 11, and 15) against CCl₄-induced cytotoxicity on liver was determined. Compounds 1, 2, 4, 7, 8 and 15 displayed hepatoprotective activity. 6-O-α-l-(2″, 3″-di-O-trans-p-hydroxycinnamoyl)rhamnopyranosylcatalpol (2) exhibited the most potent cytoprotective effect with an EC₅₀ value of 42.5 μM (SI = 19.3) compared with biphenyldimethylesterate (DDB, EC₅₀ = 277.3 μM, SI = 9.8) and bicylo-ethanol (EC₅₀ = 279.2 μM, SI = 12.2). Among the acylated iridoid glycosides, the compounds (2 and 8) containing phenolic hydroxy groups were more active than were those lacking them.     

Aspernolides F and G,new butyrolactones from the endophytic fungus Aspergillus terreus

Two new butyrolactones: aspernolides F (6) and G (7), together with three stigmasterol derivatives: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), and stigmasta-4,6,8(14), 22-tetraen-3-one (3), two meroterpenoids: terretonin A (4) and terretonin (5), and a butyrolactone derivative: butyrolactone VI (8) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were determined by spectroscopic means (1D, 2D NMR, and HRESIMS), as well as optical rotation measurement and comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 displayed a potent activity against MRSA and C. neoformans with IC₅₀ values of 0.96 μg/mL and 4.38 μg/mL, respectively compared to ciprofloxacin (IC₅₀ 0.07 μg/mL) and amphotericin B (IC₅₀ 0.34 μg/mL), respectively. While, 6 showed good activity against C. neoformans (IC₅₀ 5.19 μg/mL) and mild activity against MRSA (IC₅₀ 6.39 μg/mL). Moreover, 1 and 2 exhibited very good anti-leishmanial activity towards L. donovani with IC₅₀ values of 4.61 and 6.31 μg/mL, respectively and IC₉₀ values of 6.02 and 16.71 μg/mL, respectively.     

Artostyracins A–C,three new isoprenylated 2-arylbenzofurans from Artocarpus styracifolius

Three new isoprenylated 2-arylbenzofurans, namely artostyracins A–C (1–3, resp.), together with a known one (4), were isolated from the root of Artocarpus styracifolius Pierre. Their structures were determined by spectroscopic methods (1D and 2D NMR, UV, IR, and HR-ESI-MS). All of the compounds were evaluated for the anti-respiratory burst properties using a cellular model reproduced by chemical stimulation of rat neutrophils. Compounds 1 and 3 offered the potently inhibitory effects on respiratory burst of rat neutrophils with IC₅₀ values of 1.42 and 1.91 μM, while compounds 2 and 4 revealed moderate suppression activity with IC₅₀ values of 11.56 and 46.91 μM.     

Lignan glycosides from the Rhizomes of Smilax trinervula and their Biological activities

Phytochemical investigation of the rhizomes of Smilax trinervula led to isolation and structure elucidation of eight lignan glycosides, including five new lignans, namely, (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4′-O-β-d-glucopyranoside (1), (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4-O-β-d- glucopyranoside (2) (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-4′, 7-epoxy-8, 5′-neolignan 9′-O-β-d-glucopyranoside (3), (7R, 8R)-4, 9, 9′-trihydroxy-3, 5-dimethoxy-7.O.4′, 8.O.3′- neolignan 9′-O-β-d-glucopyranoside (4), and (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-8, 4′-oxy-neolignan 4-O-β-d-glucopyranoside (5), along with three known compounds (6-8). Their structures were established mainly on the basis of 1D and 2D NMR spectral data, ESI–MS and comparison with the literature. Compounds 1-8 were tested in vitro for their cytotoxic activity against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Compounds 3 and 5 exhibited cytotoxic activity against Lovo cells, with IC₅₀ value of 10.4 μM and 8.5 μM, respectively.     

Cytotoxic abietane-derivative diterpenoids of Salvia lachnostachys

A bioassay-guided fractionation of Salvia lachnostachys Benth leaf extract led to the isolation of three known diterpenes, namely fruticuline A (1), fruticuline B (2) and 7,20-dihydrofruticuline A (3), together with two new compounds, 4 and 5. The structures were mainly elucidated by 1D and 2D NMR spectroscopy and HRESIMS. The cytotoxic activity of the crude ethanol extract, the semi-purified fractions (A-E) and compounds 1, 2 and 4 were evaluated against seven human cancer cell lines and the normal cell line HaCat. The ethanol extract showed activity against all tested cell lines (GI₅₀ 25.0⿿44.0 μg/mL). Among the fractions, the greatest activity was exhibited by fraction A (eluted with hexane), which inhibited the growth of all tested cell lines with GI₅₀ of 3.9⿿19.5 μg/mL. Compounds 1 and 4 were the most active, inhibiting the growth of U251, MCF-7, NCI-ADR/RES, 786.0, NCI-H460, PC-3, OVCAR-03 and HaCat cell lines with GI₅₀ < 10 μM. Compound 2 showed moderate activity against MCF-7, NCI-H460, OVCAR-03, K562 and HaCat, with GI₅₀ varying 19.9⿿29.3 μM.     

Voulkensin C–E,new 11-oxocassane-type diterpenoids and a steroid glycoside from Caesalpinia volkensii stem bark and their antiplasmodial activities

A bioassay guided isolation of potential antimalarial molecules from the stem bark of Caesalpinia volkensii Harms (Fabaceae) achieved three new 11-oxocassane-type diterpenoids named voulkensin C (1), D (2) and E (3) together with one steroid glycoside named 3-O-[β-glucopyranosyl(1→2)-O-β-xylopyranosyl]-stigmasterol (4) and seven other known compounds including stigmasterol (5), β-sitosterol (6), oleanolic acid (7), 3-β-acetoxyolean-12-en-28-methyl ester (8), voucap-5-ol (9), caesadekarin C (10), deoxycaesaldekarin C (11). The structures of the new compounds were determined on the basis of extensive spectroscopic data (IR, MS, ¹H and ¹³C NMR and 2D NMR) analyses. The polar extracts revealed moderate to good antiplasmodial activities against chloquine-sensitive (D6) and -resistant strains (W2) of Plasmodium falciparum. Whereas the pure isolates exhibited limited to moderate antiplasmodial activities with compound 4 showing the highest antiplasmodial activities (IC₅₀ values of 4.44 ± 0.88 and 2.74 ± 1.10 μM against D6 and W2 strains, respectively). These results suggest a possible contribution of phytochemicals from C. volkensii stem bark towards inhibition of plasmodial parasites’ growth hence potential antimalarial.     

Phytochemical investigation of Tephromela atra: NMR studies of collatolic acid derivatives

Six known compounds, atranorin (1) and its derivatives methyl β-orcinol carboxylate (2) and methyl haematommate (3), the depsidones α-alectoronic acid (4) and α-collatolic acid (5), with its hydrolysis derivative β-collatolic acid (6), and a new compound, deoxycollatolic acid (7) have been isolated from the lichen Tephromela atra (Huds.) Hafellner (syn. Lecanora atra). The characterization of the new compound 7 was carried out by extensive NMR studies using COSY, HMQC, HMBC in addition to other spectroscopic methods. ¹H NMR spectra recorded at low temperature showed β-collatolic acid (6) was corresponding to an equilibrium of conformers.Compounds 5 and 6 showed a better superoxide anion scavenging activity (IC₅₀ = 463 and 122 μM, respectively) than quercetin (IC₅₀ = 754 μM).     

β-Secretase (BACE1)-inhibiting C-methylrotenoids from Abronia nana suspension cultures

Suspension cultures of Abronia nana were established to produce C-methylisoflavones. A new C-methylrotenoid, named abronione A (2), was isolated along with three known rotenoids, boeravinone D (1), boeravinone A methyl ether (3), and mirabijalone D (4). The IC₅₀ values of compounds 1, 2, and 4 on β-secretase (BACE1) were 4.77, 62.21, and 4.24 μM, respectively, whereas 3 was inactive. At concentrations up to 1.0 mM, the compounds did not inhibit other proteases such as trypsin, chymotrypsin, and elastase, indicating that they were specific inhibitors of β-secretase. Compounds 1 and 4 were non-competitive inhibitors based on the Dixon plot and with K_i values of 5.01 and 4.28 μM, respectively. At 50 μM, compound 4 inhibited Aβ_1–42 production by 43.7% in APP_SW-N2a cells.     

Comparing anti-HIV,antibacterial, antifungal,micellar, and cytotoxic properties of tricarboxylato dendritic amphiphiles

Three series of homologous dendritic amphiphiles—RCONHC(CH₂CH₂COOH)₃, 1(n); ROCONHC(CH₂CH₂COOH)₃, 2(n); RNHCONHC(CH₂CH₂COOH)₃, 3(n), where R = n-C_nH_2n+1 and n = 13–22 carbon atoms—were assayed for their potential to serve as antimicrobial components in a topical vaginal formulation. Comparing epithelial cytotoxicities to the ability of these homologues to inhibit HIV, Neisseria gonorrhoeae, and Candida albicans provided a measure of their prophylactic/therapeutic potential. Measurements of the ability to inhibit Lactobacillus plantarum, a beneficial bacterium in the vagina, and critical micelle concentrations (CMCs), an indicator of the potential detergency of these amphiphiles, provided additional assessments of safety. Several amphiphiles from each homologous series had modest anti-HIV activity (EC₅₀ = 110–130 μM). Amphiphile 2(18) had the best anti-Neisseria activity (MIC = 65 μM), while 1(19) and 1(21) had MICs against C. albicans of 16 and 7.7 μM, respectively. Two measures of safety showed promise as all compounds had relatively low cytotoxic activity (EC₅₀ = 210–940 μM) against epithelial cells and low activity against L. plantarum, 1(n), 2(n), and 3(n) had MICs ? 490, 1300, and 940 μM, respectively. CMCs measured in aqueous triethanolamine and in aqueous potassium hydroxide showed linear dependences on chain length. As expected, the longest chain in each series had the lowest CMC—in triethanolamine: 1(21), 1500 μM; 2(22), 320 μM; 3(22), 340 μM, and in potassium hydroxide: 1(21), 130 μM; 3(22), 40 μM. The CMC in triethanolamine adjusted to pH 7.4 was 400 μM for 1(21) and 3900 μM for 3(16). The promising antifungal activity, low activity against L. plantarum, relatively high CMCs, and modest epithelial cytotoxicity in addition to their anti-Neisseria properties warrant further design studies with dendritic amphiphiles to improve their safety indices to produce suitable candidates for antimicrobial vaginal products.