New Derivatives of Nonactic and Homononactic Acids from Bacillus pumilus Derived from Breynia fruticosa

Six new nonactic and homononactic acid derivatives, ethyl homononactate ( 1 ), ethyl nonactate ( 2 ), homononactyl homononactate ( 6 ), ethyl homononactyl nonactate ( 7 ), ethyl homononactyl homononactate ( 8 ), and ethyl nonactyl nonactate ( 9 ), as well as four known compounds, homononactic acid ( 3 ), nonactic acid ( 4 ), homononactyl nonactate ( 5 ), and bishomononactic acid ( 10 ), were isolated from culture broth of Bacillus pumilus derived from Breynia fruticosa. The structures of new compounds were elucidated by spectroscopic analysis and chemical methods. The optical purities of 1 – 6 were determined by HPLC/MS after treatment with L ‐phenylalanine methyl ester. The dimeric compounds 5 – 9 showed weak cytotoxic activities against five human cancer cell lines (IC₅₀ 19–100 μg/ml).     

Alkaloids from the roots of Stemona javanica (Kunth) Engl. (Stemonaceae) and their anti-malarial,acetylcholinesterase inhibitory and cytotoxic activities

Two new protostemonine-type alkaloids, javastemonine A and B (3 and 4) have been isolated from the root extracts of Stemona javanica together with four known Stemona alkaloids, 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (1), isoprotostemonine (2), protostemonine and isomaistemonine. The structures and relative configurations of the new alkaloids were determined by spectroscopic analysis. The alkaloids 1 and 2 and protostemonine showed moderated antiplasmodial activities against the Plasmodium falciparum strains, TM4 (IC₅₀ values of 17.7 ± 3.7, 16.8 ± 5.4, 16.0 ± 4.2 μg/mL, respectively) and K1 (IC₅₀ values of 16.8 ± 3.1, 14.1 ± 3.7, 11.9 ± 3.3 μg/mL, respectively). These compounds showed no significant cytotoxicities against KB or Vero cells or acetylcholinesterase inhibitory activities.     

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC₅₀ values of 7.14 ± 1.75 and 7.73 ± 0.24 μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC₅₀ value of 17.03 ± 0.09 μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC₅₀ values ranging from 60.20 ± 1.09 to 92.85 ± 1.12 μM. Except compounds 3, 8, and 18 were inactive.     

Novel inhibitors of urease from Corydalis govaniana Wall.

A new compound govaniadine (1), along with three known tetrahydroprotoberberine-type alkaloids caseadine (2), caseamine (3), and protopine (4), were isolated from the plant Corydalis govaniana Wall. All alkaloids 1–4 exhibited a good urease enzyme inhibition with IC₅₀ ± S.E.M. values of 20.2 ± 3.6, 38.9 ± 2.8, 66.7 ± 1.2, and 54.1 ± 1.2 μM, respectively, which are comparable to the standard inhibitor, acetohydroxamic acid (IC₅₀ = 42.0 μM). None of these compounds showed inhibition against α-chymotrypsin. This is the first report of urease inhibiting tetrahydroprotoberberine-type alkaloids.     

Spirostanols from the roots and rhizomes of Trillium tschonoskii

Two novel spirostanols, (23S,24R,25S)-18-norspirost-1,4,13-triene-21,23,24-triol-3,15-dione (1) and (23S,24S,25S)-spirost-5-ene-1β,3β,21,23,24-pentaol (2), a new natural product (3), and two known analogues (4 and 5) were isolated from the ethyl acetate-soluble portion of the ethanolic extract of Trillium tschonoskii Maxim. Their structures were elucidated by extensive spectroscopic analyses, and their cytotoxic activities on four kinds of human tumor cells were studied in vitro. Compound 4 showed significant cytotoxic activity against MCF-7 and A549 with IC₅₀ values of 6.16 ± 2.21 and 28.5 ± 11.5 μM, respectively, while 5 exhibited selective cytotoxicity against A549 with an IC₅₀ value of 13.0 ± 4.51 μM.     

Anti-osteoporotic and antioxidant activities of chemical constituents of the aerial parts of Ducrosia ismaelis

A new pterocarpan glycoside, glycinol-3-O-β-d-glucopyranoside (1), and a new dihydrochalcone glycoside, ismaeloside A (2), were isolated together with 13 known compounds, including several flavonoids (3–8), lignans (9–11), and phenolic compounds (12–15), from the methanol extract of the aerial parts of Ducrosia ismaelis. The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The anti-osteoporotic and antioxidant activities of the isolated compounds were assessed using tartrate-resistant acid phosphatase (TRAP), oxygen radical absorbance capacity (ORAC), and reducing capacity assays. Compound 15 exhibited a dose-dependent inhibition of osteoclastic TRAP activity with a TRAP value of 86.05 ± 6.55% of the control at a concentration of 10 μM. Compounds 1, 3–5, and 8 showed potent peroxyl radical-scavenging capacities with ORAC values of 22.79 ± 0.90, 25.57 ± 0.49, 20.41 ± 0.63, 26.55 ± 0.42, and 24.83 ± 0.12 μM Trolox equivalents (TE) at 10 μM, respectively. Only compound 9 was able to significantly reduce Cu(I) with 23.44 μM TE at a concentration of 10 μM. All of the aforementioned compounds were isolated for the first time from a Ducrosia species.     

Withaphysalin-type withanolides from Physalis minima

Nine new withaphysalin-type withanolides (1–9), named physaminimins (G-O) were isolated from the whole plants of Physalis minima Linn. The structures of these compounds were elucidated based on spectroscopic methods (1D NMR, HSQC, HMBC, ROESY) and HRESIMS. Physaminimins G, H, and K showed inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a macrophage (RAW264.7) cells with IC₅₀ values of 17.41 ± 1.04, 36.33 ± 1.95 and 21.48 ± 1.67 μM, respectively.     

Bioactive norditerpenoids from the soft coral Sinularia gyrosa

Chemical investigations of the soft coral Sinularia gyrosa resulted in the isolation of six new norcembranolides, gyrosanolides A–F (1–6), a new norcembrane, gyrosanin A (7), and 11 known norditerpenoids 8–18. The structures of the isolated compounds were elucidated through extensive spectroscopic data and by comparison with reported data in the literature. Compounds 1–3, 7–9, 12, and 13 at concentration of 10 μM did not inhibit the COX-2 protein expression, but significantly reduced the levels of the iNOS protein (55.2 ± 14.6%, 18.6 ± 6.7%, 10.6 ± 4.6%, 66.9 ± 5.2%, 10.2 ± 5.1%, 17.4 ± 7.2%, 47.2 ± 11.9%, and 56.3 ± 5.1%, respectively) by LPS stimulation. Compound 8 showed significant antiviral activity against HCMV (human cytomegalovirus) cells with an IC₅₀ of 1.9 μg/mL.     

Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia,and synthesis and structure–activity relationships of related compounds

Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6–9). The structures of the two new compounds were elucidated based on analyses of their 1D and 2D NMR spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the strongest antiplasmodial activity among all the isolated compounds, with IC₅₀ values of 0.4 ± 0.1 and 0.2 ± 0.1 μM, respectively. The two new compounds displayed modest activities, with IC₅₀ values of 26 ± 4 and 9 ± 1 μM, respectively. Due to the synthetic accessibility of the new compounds and the increased activity shown by the dimeric compounds, a structure–activity relationship study was conducted. As a result, one analogue of kniphofione B (4), the caffeic acid derivative of aloe-emodin, was found to have the highest activity among all the aloe-emodin derivatives, with an IC₅₀ value of 1.3 ± 0.2 μM.     

Terpenoids with cytotoxic activity from the branches and leaves of Pyrus pashia

Twenty terpenoids, including a new triterpenoid (1) and a new monoterpenoid (20), were isolated from the branches and leaves of Pyrus pashia. The structures of two new compounds were determined to be 2α, 3β, 27-trihydroxyolean-12-en-28-oic acid (1) and (4α)-3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol 3-O-β-d-glucopyranoside (20) on the basis of spectroscopic analysis (IR, HRESIMS, 1D and 2D NMR) and chemical method. Some of the isolated compounds were evaluated for their cytotoxic activity against a panel of human cancer cell lines by MTT assay, using cisplatin as a positive control. Compound 14 exhibited cytotoxic activities against A549 (IC₅₀ = 19.18 ± 4.26 μM), Hela (IC₅₀ = 12.56 ± 3.89 μM), SGC7901 (IC₅₀ = 10.48 ± 1.95 μM) and NHI-1975 (IC₅₀ = 7.38 ± 2.31 μM) cell lines as well as compound 12 displayed cytotoxic activities against A549 (IC₅₀ = 14.71 ± 1.47 μM) and Hela (IC₅₀ = 12.22 ± 1.88 μM) cell lines.     

Dihydrochalcone glucosides and antioxidant activity from the roots of Anneslea fragrans var. lanceolata

Bioassay-guided fractionation of the roots of Anneslea fragrans var. lanceolata led to the isolation of four dihydrochalcone glucosides, davidigenin-2′-O-(6″-O-4″′-hydroxybenzoyl)-β-glucoside (1), davidigenin-2′-O-(2″-O-4″′-hydroxybenzoyl)-β-glucoside (2), davidigenin-2′-O-(3″-O-4″′-hydroxybenzoyl)-β-glucoside (3), and davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), and 13 known compounds. The structures were identified by means of spectroscopic analysis. Davidigenin-2′-O-(6″-O-syringoyl)-β-glucoside (4), 1-O-3,4-dimethoxy-5-hydroxyphenyl-6-O-(3,5-di-O-methylgalloyl)-β-glucopyranoside (5), lyoniresinol (10), and syringic acid (13) showed ABTS [2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)] cation radical scavenging activity, with SC₅₀ values of 52.6 ± 5.5, 26.0 ± 0.7, 6.0 ± 0.2, and 27.5 ± 0.6 μg/mL in 20 min, respectively. Lyoniresinol (10), isofraxidin (12), and syringic acid (13) also showed DPPH [1,1-diphenyl-2-picrylhydrazyl] radical scavenging activity, with SC₅₀ values of 8.4 ± 1.8, 51.6 ± 2.2, and 4.3 ± 0.7 μg/mL in 30 min, respectively.     

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.     

Geranylated tetraoxygenated xanthones from the pericarp of Garcinia pedunculata

Three new xanthones, pedunxanthones D-F (1–3), along with ten known compounds, were isolated from a chloroform extract of the pericarp of Garcinia pedunculata. Their structures were determined using spectroscopic techniques. Cytotoxicity against HeLa and NCI-H460 cells of the isolated compounds using an SRB assay was evaluated with pedunxanthone D (1) as the most active compound (IC₅₀ 24.9 ± 0.4 and 26.1 ± 1.5 μg/ml, respectively).     

Anticancer and α-chymotrypsin inhibiting diterpenes and triterpenes from Salvia leriifolia

Salvialeriol (1), a new abietane-type diterpene, was isolated from Salvia leriifolia Benth. (Salvia leriaefolia), along with two known abietane-type diterpenoids, 6-hydroxysalvinolone (2) and deacetylnemorone (3), and two known triterpenes, 2-acetoxylupeol (4), and lupine-2,3-diol (5). Compounds 2–5 are reported here for the first time from this species. Compound 4 was previously reported as a synthetic derivative of 5 and this is the first report of its isolation from a natural source. Compounds 2, 3 and 5 exhibited a potent antiproliferative activity against the prostate cancer cell lines (PC3) with IC₅₀ of 3.9 ± 0.1, 6.2 ± 0.1 and 2.8 ± 0.1 μM, respectively, and cervical cancer cell lines (HeLa) with IC₅₀ of 8.0 ± 0.3, 2.6 ± 0.1 and 2.7 ± 0.1 μM, respectively. Whereas compounds 1 and 4 showed moderate antiproliferative activities against the cell lines. Compounds 1–5 were also evaluated for the inhibition of α-chymotrypsin, a protease enzyme, and 2 exhibited a competitive inhibition of the enzyme (IC₅₀ = 188.8 μM).     

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3–26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10–21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC₅₀ values as low as 18.05 ± 1.17, 18.64 ± 1.83, and 17.23 ± 0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3–6, 8, 18, 20–23, and 25–26 inhibited the production of both NO and TNF-α, with IC₅₀ values ranging from 11.1 ± 0.9 to 45.3 ± 1.6 μM and 14.4 ± 0.5 to 44.5 ± 1.2 μM, respectively.     

Prenylated C6–C3 compounds from the roots of Illicium henryi

Eleven prenylated C₆–C₃ compounds, illihenryifunones A, B (1, 2), illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A−G (5–11), and three known prenylated C₆–C₃ compounds (12–14), were isolated from the roots of Illicium henryi. Structures of 1–11 were elucidated by spectroscopic methods including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol moiety in 5 was determined by observing its induced circular dichroism after addition of Mo₂(OAc)₄ in DMSO. The absolute configuration of C-11 in 4 was determined as S based on the Rh₂(OCOCF₃)₄-induced CD data; the absolute configuration of 3 was determined as R by comparison of its experimental and calculated electronic circular dichroism (ECD). The antioxidant activities of compounds 1–14 were also evaluated. Compound 4 exhibited strong antioxidant activity with an IC₅₀ value of 2.97 ± 1.30 μM, whereas compounds 3 and 8 showed antioxidant activities with IC₅₀ values of 44.36 ± 0.30 and 48.00 ± 2.01 μM, respectively.     

Dammarane-type saponins from Gynostemma pentaphyllum

Dammarane-type saponins, gypenosides VN1–VN7 (1–7), were isolated from the total saponin extract of Gynostemma pentaphyllum aerial parts, with their structures elucidated on the basis of spectroscopic and chemical methods. These compounds showed moderate cytotoxic activity against four human cancer cell lines, A549 (lung), HT-29 (colon), MCF-7 (breast), and SK-OV-3 (ovary), with IC₅₀ values ranging from 19.6 ± 1.1 to 43.1 ± 1.0 μM. Regarding the HL-60 (acute promyelocytic leukemia) cell line, compounds 1, 5, and 6 showed weakly active with IC₅₀ values of 62.8 ± 1.9, 72.6 ± 3.6, and 82.4 ± 3.2 nM, respectively, while 2, 3, 4, and 7 were less active with IC₅₀ values >100 μM.     

Pencitrin and pencitrinol,two new citrinin derivatives from an endophytic fungus Penicillium citrinum salicorn 46

Two new citrinin derivatives, pencitrin (1) and pencitrinol (2), and a known compound citrinin (3), together with its two known dimers, penicitrinone A (4), penicitrinone E (5), were isolated from an endophytic fungus P. citrinum 46 derived from Salicornia herbacea Torr. by adding CuCl₂ into fermentation medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configurations of 1, 4, and 5 were determined by comparison of quantum chemical time-dependent density functional theory (TDDFT) calculated and electronic circular dichroism (ECD) spectra. Compound 1 exhibited potent cytotoxic activities towards A549 human lung cancer cells and HepG2 human liver cancer cells with IC₅₀ values of 23.73 ± 3.61 and 35.73 ± 2.15 μM, respectively, whereas compound 5 showed moderate cytotoxic activities towards A549 and HepG2 cancer cells with IC₅₀ values of 40.47 ± 4.52 and 53.57 ± 3.24 μM, respectively. The results from the current research highlighted the effectiveness and usefulness of the pipeline to discover novel bioactive fungal secondary metabolites by modification of the culture media.     

Design,synthesis and biological evaluation of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel histone deacetylase inhibitors

A series of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC₅₀ values of compound 10r against HDAC1, HDAC3, HDAC6 was 1.14 ± 0.03 nM, 3.56 ± 0.08 nM, 11.43 ± 0.12 nM. Compound 10r noticeably up-regulated the level of histone H3 acetylation compared to the SAHA. Most of the compounds showed the strong anti-proliferative activity against human cancer cell lines including RMPI8226 and HCT-116. The IC₅₀ values of Compounds 10r and 10t against RPMI8226 was 2.39 ± 0.20 μM, 1.41 ± 0.44 μM, respectively, and the HCT-116 was sensitive to the compounds 10h, 10m, 10r, 10w with the IC₅₀ values <1.9 μM.     

Isolation of antioxidant constituents from Combretum apiculatum subsp. apiculatum

Species of the family Combretaceae are used extensively in traditional medicine against inflammation and infections, and although antibacterial activity has been reported in non-polar extracts, further rationale for the widespread use of the Combretaceae is expected to exist. Methanol extracts of leaves of ten different Combretum species were evaluated for antioxidant activity by spraying TLC chromatograms of each leaf extract with 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds with antioxidant activity were detected by bleaching of the purple DPPH colour. Leaf extracts of Combretum apiculatum subsp. apiculatum had the most antioxidant compounds. This species was consequently selected for phytochemical investigation. A DPPH assay-directed fractionation of the leaf extracts of C. apiculatum led to the isolation of four antioxidant compounds from the ethyl acetate and butanol soluble fractions. The structures of the compounds were determined by spectroscopic analyses (¹H-NMR, ¹³C-NMR and MS) and identified as: cardamonin (1), pinocembrin (2), quercetrin (3) and kaempferol (4). In a quantitative antioxidant assay, the more polar fractions (ethyl acetate and butanol) obtained by solvent–solvent fractionation had the highest antioxidant activity among the solvent fractions obtained from C. apiculatum, with EC₅₀ values of 3.91 ± 0.02 and 2.44 ± 0.02 μg/ml respectively. Of the four isolated compounds, quercetrin (4) and kaempferol (3) had the strongest antioxidant activity, with EC₅₀ values of 11.81 ± 85 and 47.36 ± 0.03 μM respectively. Cardamonin (1) and pinocembrin (2) did not demonstrate strong activity. L-ascorbic acid was used as standard antioxidant agent (EC₅₀ = 13.37 ± 0.20 μM or 2.35 μg/ml). The cytotoxicity of cardamonin and pinocembrin was evaluated on Vero kidney cells using the MTT (3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide) assay with berberine as positive control. At concentrations higher than 50 μg/ml of cardamonin or pinocembrin, the cells were not viable. Cardamonin was more toxic (LC₅₀ = 1.97 μg/ml) than pinocembrin (LC₅₀ = 29.47 μg/ml) and even the positive control, berberine (LC₅₀ = 12.35 μg/ml).