Seven new meroditerpenoids, from the marine sponge Strongylophora strongylata, that inhibited the maturation of starfish oocytes

Seven new meroditerpenoids, strongylophorines 13-19 (1-7), have been isolated together with the four known strongylophorines 2 (8), 3 (9), 4 (10), and 8 (11) by a screening method using oocytes of the starfish Asterina pectinifera from a marine sponge Strongylophora strongylata collected at Iriomote Island, Okinawa, Japan. The structures were assigned according to their spectral data. Ten strongylophorines inhibited the maturation of starfish oocytes in the range 1.1-37.6 μM (IC₅₀), while strongylophorine 4 (10) was not active at 250 μM.     

The anti-inflammatory activity of several flavonoids isolated from Murraya paniculata on murine macrophage cell line and gastric epithelial cell (GES-1)

Context Murraya paniculata (L.) Jack (Rutaceae), Qianlixiang in Chinese, is distributed in China. As an important traditional Chinese medicine (TCM), it demonstrates many bioactivities, such as febrifuge, astringent, anti-dysenteric, and tonic.

Objective: The objective of this study is to evaluate the anti-inflammatory effect of three flavonoids isolated from M. paniculata in lipopolysaccharide (LPS)-activated murine macrophage cell line and ethanol-induced gastric damage on gastric epithelial cell (GES-1).

Materials and methods Three identified flavonoids were isolated from stems and leaves of M. paniculata using ultra performance liquid chromatography (UPLC). Cell viability was measured with MTT, mouse peritoneal macrophages and GES-1 cells were incubated with 0, 0.01, 0.1, 1, 10, and 100?μM P1, P3 and P8 for 24, 48, and 72?h. The inhibitory effect of pretreatment with various concentrations of 5,7,3′,4′,5′-pentamethoxyflavone (P1), 5,7,3′,4′-tetramethoxyflavone (P3), or 5-desmethylnobiletin 5-hydroxy-6,7,8,3′,4′-pentameth-oxyflavone (P8) ranging from 0.03 to 30?μM on nitric oxide (NO) secretion was quantified by the Griess assay for 24 and 48?h, while interleukin-6 (IL-6) was measured by ELISA for 24 and 48?h.

Results The effects of P1, P3, and P8 on mouse peritoneal macrophages and GES-1 cells were not attributable to cytotoxic effects at the doses of 0–10?μM. The IC₅₀ value of P1 is 53.40?μM, P3 is 120.98?μM, and P8 is 10.73?μM. The concentration of the three flavonoids had the best effects of anti-inflammation upon NO inhibition at the dose of 3?μM. P3 had the highest inhibition on IL-6 production. The GES-1 cells pretreated with three flavonoids showed a significant increase in the level of NO (P1: 7.94?±?0.0635?μM, P3: 8.81?±?0.0159?μM, and P8: 8.51?±?0.0522?μM) at 24?h and a more significant increase at 48?h (P1: 9.34?±?0.0975?μM, P3: 11.9?±?0.0672?μM, and P8: 9.34?±?0.0454?μM).

Discussion and conclusion The current results suggested that the anti-inflammatory activity of three flavonoids was mainly manifested in the reduction of production of NO and IL-6 production. Analysis of the structure–activity relationship indicated that the double bond at C₂–C₃ and the position of the B ring at C₂/C₃ seemed to be indispensable for the anti-inflammatory activity.     

In vitro anti-inflammatory components isolated from the carnivorous plant Nepenthes mirabilis (Lour.) Rafarin

Context: Nepenthes mirabilis (Lour.) Rafarin (Nepenthaceae) is a carnivorous plant used as a folk medicine in the treatment of jaundice, hepatitis, gastric ulcers, ureteral stones, diarrhea, diabetes, and high blood pressure. Neither the phytochemical content nor biological activities of N. mirabilis have been reported.

Objective: The anti-inflammatory activity from the N. mirabilis methanolic extract led to the isolation of compounds (1–26).

Materials and methods: Chromatographic methods were used to isolate compounds from the methanol extract of N. mirabilis branches and leaves. The anti-inflammatory activity of these isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) using ELISA. Primary BMDCs were used to examine the production of pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-α, at concentrations of 0.1, 0.2, and 1.0?μM) as compared with a positive control, SB203580 (1.0?μM). MTT assays showed that isolated compounds (1–26) did not exhibit significant cytotoxicity at concentrations up to 20.0?μM.

Results: Compound 9 showed potent inhibition of IL-12 p40, IL-6, and TNF-α production (IC₅₀?=?0.17?±?0.02, 0.46?±?0.01, and 8.28?±?0.21?μM, respectively). Compound 4 showed potent inhibition of IL-12 p40 and IL-6 production (IC₅₀?=?1.17?±?0.01 and 2.15?±?0.04?μM). In addition, IL-12 p40 inhibition by naphthalene derivatives (1–7, 9, and 10), phenolic compounds (11–15), lupeone (18), and flavonoids (22, 25, and 26) was more potent than with the positive control. The isolated compounds exhibited little and/or no inhibitory effects on TNF-α production in LPS-stimulated BMDCs.

Discussion and conclusion: Taken together, these data suggest that the isolated components have significant inhibitory effects on pro-inflammatory cytokine production and warrant further study concerning their potential medicinal use.     

Isolation and identification of phase I metabolites of butyrolactone I in rats

1.?Butyrolactone I (BL-I), one of the major secondary metabolites of fungus Aspergillus terreus, is a selective cdc2 kinase inhibitor. In the present study, the metabolism of BL-I in male Wistar rats was investigated by characterizing metabolites excreted into feces.

2.?Following an oral dose of 40?mg/kg BL-I, 10 phase I metabolites were isolated from the feces of rats, and their structures were identified on the basis of a range of spectroscopic data and ICD analysis. These metabolites were fully characterized as butyrolactone VI (M1), aspernolide E (M2), 7′′S-hydroxy-9′′-ene-butyrolactone I (M3), 7′′R-hydroxy-9′′-ene-butyrolactone I (M4), 7″S, 8″R-dihydroxy-aspernolide E (M5), 7″R, 8″S-dihydroxy-aspernolide E (M6), 7″R-acetyl-8″S-hydroxy-aspernolide E (M7), 7″S-acetyl-8″R-hydroxy-aspernolide E (M8), 7″R-methoxy-8″S-hydroxy-aspernolide E (M9), butyrolactone V (M10), respectively. It is the first time to describe the metabolites of BL-I in vivo, and metabolites M3 to M9 are new compounds.

3.?BL-I and metabolites M2 to M10 were evaluated for their antimicrobial activity and in vitro antiproliferative activities. Only M-3 and M-4 showed inhibitory effect against staphylococcus aureus both with MIC of 125?μg/ml. BL-I and metabolites M-4 and M-5 exhibited potent cancer cell growth inhibitory activities against HL-60 (human leukemia) cell lines with the IC₅₀ values of 13.2, 28.8 and 35.7?μM, respectively.

4.?On the basis of metabolites profile, a possible metabolism pathway for BL-I in rats has been proposed. This is the first systematic study on the phase I metabolites of BL-I.     

Chemical constituents of the red alga Laurencia tristicha

Six new sesquiterpenes, 10-hydroxy-epiaplysin (1), 10-hydroxy-aplysin (2), 10-hydroxy-debromoepiaplysin (3), aplysin-9-ene (4), epiaplysinol (5) and debromoepiaplysinol (6), together with 13 known compounds (7–19), have been isolated from the red alga Laurencia tristicha. The structures of 1–6 were determined by spectroscopic methods including IR, EI-MS, HREI-MS, and 1D and 2D NMR techniques. All compounds were obtained from this species for the first time and were tested for cytotoxic activities against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), hepatoma (Bel 7402), colon cancer (HCT-8) and HeLa cell lines. Compound 6 showed selective cytotoxicity against HeLa cell line with IC₅₀ 15.5 μM, cholest-5-en-3β,7α-diol (14) was toxic to all tested cell lines with IC₅₀ values of 16.8, 5.1, 0.5, 0.5, and 0.3 μM, respectively, and other compounds were inactive (IC₅₀>10 μg/ml).     

Antioxidant and cytotoxic lignans from the roots of Bupleurum chinense

In the search for biologically active compounds from the roots of Bupleurum chinense D C., phytochemical investigation of its ethanol extract led to the isolation and identification of a new 8-O-4′ neolignan glucoside, saikolignanoside A (1), along with eight known lignans (2–9). Their structures were determined on the basis of IR, UV, HRESIMS, and NMR spectroscopic analyses. The antioxidant and cytotoxic effects of isolated compounds were evaluated in vitro. The isolated compounds (IC₅₀ > 200 μM) did not display 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Whereas compounds 1–2, 5, 7, and 9 exhibited potent 2, 2′-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging properties with IC₅₀ values ranging from 8.34 to 15.24 μM, while compounds 3–4, 6, 8 showed moderate properties. In addition, all compounds were evaluated for cytotoxicities against A549, HepG2, U251, Bcap-37, and MCF-7 cell lines. Compounds 5 and 9 (IC_50?相似文献   

Anti-inflammatory coumarins from Paramignya trimera

Context: Paramignya trimera (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.

Objective: This study investigated chemical constituents of the P. trimera stems and evaluated anti-inflammatory effects of isolated compounds.

Materials and methods: Cytotoxicity of isolated compounds (5–40?μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24?h. Inhibitory effects of isolated compounds (5-40?μM) on nitrite and PGE₂ concentrations were determined using Griess reaction and PGE₂ ELISA kit, respectively (pretreated with the compounds for 3?h and then stimulated for 18?h with LPS). Inhibitory effects of compounds (5-40?μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3?h and then stimulated for 24?h with LPS).

Results: Seven coumarins were isolated and identified as: ostruthin (1), ninhvanin (2), 8-geranyl-7-hydroxycoumarin (3), 6-(6′,7′-dihydroxy-3′,7′-dimethylocta-2′-enyl)-7-hydroxycoumarin (4), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (5), 6-(2-hydroxyethyl)-2,2-dimethyl-2H-1-benzopyran (6), and luvangetin (7). Compounds 1–4 and 7 inhibited NO and PGE₂ production in LPS-stimulated BV2 cells, with IC₅₀ values ranging from 9.8 to 46.8 and from 9.4 to 52.8?μM, respectively. Ostruthin (1) and ninhvanin (2) were shown to suppress LPS-induced iNOS and COX-2 protein expression.

Discussion and conclusion: The present study provides a scientific rationale for the use of P. trimera in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.     

Antiprotozoal activity of extracts and isolated triterpenoids of ‘carnauba’ (Copernicia prunifera) wax from Brazil

Context: ‘Carnauba’ wax is a natural product obtained from the processing of the powder exuded from Copernicia prunifera (Miller) H. E. Moore (Arecaceae). This material is widely used in the Brazilian folk medicine, including the treatment of rheumatism and syphilis.

Objective: To investigate the antiprotozoal activity of hexane and EtOH extracts from the ‘carnauba’ wax as well as from the isolated compounds from the bioactive extracts.

Material and methods: Two different samples of ‘carnauba’ (C. prunifera) waxes – types 1 and 4 – were individually extracted using hexane (EH) and EtOH (EE). Aliquots of hexane (type 1 – EH-1 and EH-4) and EtOH (type 4 – EE-1 and EE-4) extracts were tested against promastigote (2–200?μg/mL in DMSO during 48?h at 24?°C) and amastigote (3–150?μg/mL in DMSO during 120?h at 37?°C) forms of Leishmania infantum as well as against trypomastigote (3–150?μg/mL in DMSO during 24?h at 37?°C) forms of Trypanosoma cruzi. Bioactive extracts EH-1 and EE-4 were subjected to a bioactivity-guided fractionation to afford three dammarane-type triterpenoids (1–3). The in vitro antiprotozoal activities of the obtained compounds were evaluated as described above. Additionally, the cytotoxicity activity of compounds 1–3 against mammalian conjunctive cells (NCTC – 2–200?μg/mL in DMSO during 48?h at 37?°C) was determined.

Results: From the bioactive hexane and EtOH extracts from the ‘carnauba’ (C. prunifera) wax, were isolated three dammarane-type triterpenoids: (24R*)-methyldammar-25-ene-3β,20-diol (carnaubadiol, 1), (24R*)-methyldammara-20,25-dien-3-one (2) and (24R*)-methyldammara-20,25-dien-3α-ol (3). These compounds were identified based on the analysis of NMR and MS spectroscopic data. Compounds 1–3 were effective against the intracellular amastigotes of L. infantum, with IC₅₀ values ranging from 8 to 52?μM, while compounds 1 and 3 displayed activity against trypomastigote forms of T. cruzi with IC₅₀ values of 15 and 35?μM, respectively. The mammalian cytotoxicity assay demonstrated no damage to NCTC conjunctive cells up to 200?μM, except for compound 1, which demonstrated a CC₅₀ value of 34?μM.

Conclusion: Based on the results, it was possible to conclude that the detected antiprotozoal bioactivity of ‘carnauba’ (C. prunifera) wax extracts could be related to the presence of the natural dammarane triterpenoid derivatives. The results suggested that these compounds could be used as promising scaffolds for drug design studies for leishmaniasis and Chagas disease.     

Cytotoxic ent-kaurane diterpenoids from Isodon macrophyllus

Two new ent-kaurane diterpenoids, dayecrystals D–E (1–2), together with nine known compounds, isojaponin A (3), rabdosin A (4), lushanrubescensin J (5), wikstroemioidin B (6), maoyecrystal C (7), rabdosin B (8), isodonal (9), shikokianin (10), and effusanin A (11), were isolated from the leaves of Isodon macrophyllus. The structures of the new compounds were elucidated using 1D and 2D NMR spectroscopy. The ¹³C-NMR spectral data of compound 4 are reported for the first time. All of the compounds were tested for their cytotoxicities against DU145 and LoVo human tumor cells. Compounds 4, 10, and 11 showed inhibitory effects on DU145 cells with IC₅₀ values 5.90, 4.24, and 3.16 μM, and LoVo cells with IC₅₀ values 14.20, 17.55, and 3.02 μM, respectively.     

Indole alkaloid glucosides from the roots of Isatis indigotica

Five new indole alkaloid glucosides named isatindigotindolosides A-E (1–5), along with three known analogs (6–8), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. In the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with IC₅₀ values of 14.6–33.3 μM. Compound 1 also exhibited inhibitory effect against nitric oxide (NO) production in microglial cell BV2 with an inhibition ratio of 93.0% at 10 μM.     

Flavonoids from Vitex trifolia L. inhibit cell cycle progression at G2/M phase and induce apoptosis in mammalian cancer cells

Six flavonoids, persicogenin (1), artemetin (2), luteolin (3), penduletin (4), vitexicarpin (5) and chrysosplenol-D (6), have been isolated for the first time as new cell cycle inhibitors from Vitex trifolia L., a Chinese folk medicine used to treat cancers, through a bioassay-guided separation procedure. They were identified by spectroscopic methods. The inhibitory effects of 1–6 on the proliferation of mammalian cancer cells have been evaluated by the SRB (sulforhodamine B) method and their effects on cell cycle and apoptosis investigated by flow cytometry with the morphological observation under light microscope and by agarose-gel electrophoresis to detect internucleosomal DNA fragmentation. Compounds 1–6 inhibited the proliferation of mouse tsFT210 cancer cells with the IC₅₀s (μg?ml^?1) > 100 (inhibition rate at 100?μg?ml^?1, 47.9%) for 1, >100 (inhibition rate at 100?μg?ml^?1, 49.6 %) for 2, 10.7 for 3, 19.8 for 4, 0.3 for 5, and 3.5 for 6. Flow cytometric investigations for 1–6 demonstrated that 1–5 mainly inhibited cell cycle at the G₂/M phase in a dose-dependent manner with a weak induction of apoptosis on the tsFT210 cells, while 6 induced mainly apoptosis of the same tsFT210 cells also in a dose-dependent manner together with a weak inhibition of the cell cycle at the G₀/G₁ and G₂/M phases, demonstrating that 1–6 exert their anti-proliferative effect on tsFT210 cells through inhibiting cell cycle and inducing apoptosis. In contrast to the cell cycle G₂/M phase inhibitory main effect on tsFT210 cells, 5 induced mainly apoptosis on human myeloid leukemia K562 cells with a weak inhibition of the cell cycle at the G₂/M phase. The present result provides flavonoids 1–6 as new cell cycle inhibitors and 1 and 4 as new anticancer flavonoids, which not only provide the first example of cell cycle G₂/M phase inhibitory and apoptosis-inducing constituents of V. trifolia L. but also explain the use of Vitex trifolia L. by Chinese people to treat cancers.     

Polygonumnolides C1-C4; minor dianthrone glycosides from the roots of Polygonum multiflorum Thunb

Four new dianthrone glycosides, named polygonumnolides C1-C4 (1–4), were isolated from the dried roots of Polygonum multiflorum Thunb, together with two known emodin dianthrones (5–6). Their hepatotoxicities were evaluated against L-02 cell lines. Compounds 1–4 showed weak hepatotoxicity against L-02 cell lines with IC₅₀ values of 313.05, 205.20, 294.20, and 207.35?μM, respectively.     

Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan

Abstract

Context: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines for the treatment of many diseases. The heartwood of this plant contains various phenolic components with interesting biological applications; however, the chemical and biological potentials of the seed of this plant have not been fully explored.

Objective: This study identified the cytotoxic activity of compounds from the seeds of C. sappan.

Materials and methods: The methanol extract of the seed of C. sappan was suspended in H₂O and then partitioned with CH₂Cl₂, EtOAc, and n-BuOH, successively. Diterpenoid compounds were isolated from the CH₂Cl₂-soluble fraction by silica gel column chromatography methods using organic solvents. The compound structures were determined by detailed analysis of NMR and MS spectral data. Cytotoxic activity was measured using a modified MTT assay against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3 enzyme and western blotting assay were performed to confirm inhibitory mechanism of active compound.

Results: Five cassane-type diterpenoids were isolated and identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4), and phanginin J (5). Compounds 1–4 showed effective inhibition against HL-60 cells with the IC₅₀ values of 16.4?±?1.5, 19.2?±?2.0, 11.7?±?1.6, and 22.5?±?5.1?μM. Compounds 1–3 exhibited cytotoxic activity against HeLa cells with the IC₅₀ values of 28.1?±?3.6, 37.2?±?3.4, and 22.7?±?2.8?μM. Treatment of HL-60 cell lines with various concentrations of 3 (0–30?μM) resulted in the growth inhibition and induction of apoptosis.

Conclusion: These findings demonstrate that compound 3 (phanginin D) is one of the main active components of the seed of C. sappan activating caspases-3 which contribute to apoptotic cell death.     

A new auronol from Cudrania cochinchinensis

A new auronol, cudrauronol (1), was isolated from the roots of Cudrania cochinchinensis along with 10 known compounds, 1,3,5-trihydroxy-4-prenylxanthone (2), 1,3,7-trihydroxy-4-prenylxanthone (3), 3,4′,5,7-tetrahydroxydihydroflavonol (4), kaempferol (5), 3,6-dihydroxy-1,5-dimethoxyxanthone (6), 2′,4′,5,7-tetrahydroxyflavanolol (7), 3,7-dihydroxy-1-methoxyxanthone (8), 1,3,5-trihydroxyxanthone (9), cudraflavone B (10), and 2′-oxyresveratrol (11). Compounds 1–8 were evaluated for anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 2–5 were more active than aminoguanidine, with IC₅₀ values of 8.8, 23.2, 27.1, and 11.9 μM, respectively.     

Selective dual cholinesterase inhibitors from Aconitum laeve

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1–6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1–6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC_50?=?3.7 μM, 4.53 μM) and BChE (IC_50?=?12.23 μM, 9.94 μM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC_50?=?2.51 and 6.13 μM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.     

Bioactive steroids and sorbicillinoids isolated from the endophytic fungus Trichoderma sp. Xy24

A new steroid glucoside (1), along with nine known steroids (2–10) and four known sorbicillinoids (11–14), were isolated from the endophytic fungus Trichoderma sp. Xy24. Their structures were elucidated on the basis of spectroscopic data analyses and by comparison with reported data. Compounds 3, 5–7, 9, 10, and 13 exhibited significant inhibitory effects on HIV-1 virus with IC₅₀ values ranging 1.9–9.3 μM; compounds 10, 13, and 14 showed potent inhibitory activity on LPS-induced NO production in BV2 microglia cells with inhibitory rates of 108.2, 100, and 75.1% at 10 μM, respectively. In addition, compound 10 displayed moderate cytotoxicity against BCG823 and HePG2 cell lines with IC₅₀ values of 11.1 and 17.7 μM, respectively.     

In vitro evaluation of the inhibition and induction potential of olaparib,a potent poly(ADP-ribose) polymerase inhibitor,on cytochrome P450

1.?In vitro studies were conducted to evaluate potential inhibitory and inductive effects of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, on cytochrome P450 (CYP) enzymes. Inhibitory effects were determined in human liver microsomes (HLM); inductive effects were evaluated in cultured human hepatocytes.

2.?Olaparib did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2D6 or CYP2E1 and caused slight inhibition of CYP2C9, CYP2C19 and CYP3A4/5 in HLM up to a concentration of 100?μM. However, olaparib (17–500?μM) inhibited CYP3A4/5 with an IC₅₀ of 119?μM. In time-dependent CYP inhibition assays, olaparib (10?μM) had no effect against CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 and a minor effect against CYP3A4/5. In a further study, olaparib (2–200?μM) functioned as a time-dependent inhibitor of CYP3A4/5 (K_I, 72.2?μM and K_inact, 0.0675?min^?1). Assessment of the CYP induction potential of olaparib (0.061–44?μM) showed minor concentration-related increases in CYP1A2 and more marked increases in CYP2B6 and CYP3A4 mRNA, compared with positive control activity; however, no significant change in CYP3A4/5 enzyme activity was observed.

3.?Clinically significant drug–drug interactions due to olaparib inhibition or induction of hepatic or intestinal CYP3A4/5 cannot be excluded. It is recommended that olaparib is given with caution with narrow therapeutic range or sensitive CYP3A substrates, and that prescribers are aware that olaparib may reduce exposure to substrates of CYP2B6.     

Xanthine oxidase/tyrosinase inhibiting,antioxidant, and antifungal oxindole alkaloids from Isatis costata

Phytochemical investigations on the ethyl acetate soluble fraction of the whole plant of Isatis costata Linn. (Brassicaseae) led to the isolation of the oxindole alkaloids costinones A (1), B (2), isatinones A (3), B (4), indirubin (5), and trisindoline (6). Compounds 1–6 displayed significant to moderate inhibition against xanthine oxidase enzyme with IC₅₀ values ranging from 90.3?±?0.06 to 179.6?±?0.04 µM, whereas the standard inhibitor of xanthine oxidase (allopurinol) had an IC₅₀ value of 7.4?±?0.07 µM. Compounds 1 (IC₅₀ 7.21?±?0.05 µM), 2 (IC₅₀ 9.40?±?0.03 µM), 3 (IC₅₀ 11.51?±?0.07 µM), 4 (IC₅₀ 12.53?±?0.06 µM), 5 (IC₅₀ 14.29?±?0.09 µM), and 6 (IC₅₀ 17.34?±?0.04 µM) exhibited pronounced activities when compared with the standard tyrosinase inhibitor l-mimosine (IC₅₀ 3.70?±?0.03 µM), along with DPPH radical scavenging activity with IC₅₀ 226, 270, 300, 320, 401, and 431 µM, respectively. The crude extract and compounds 1, 2, 5, and 6 showed significant antifungal activity against Trichophyton schoen leinii, Aspergillus niger, Candida albicans, Trichophyton simii, and Macrophomina phaseolina.     

Bioassay-guided isolation and evaluation of antimicrobial compounds from Ixora megalophylla against some oral pathogens

Context Ixora megalophylla Chamch. (Rubiaceae) is a new plant species recently found in southern Thailand. Ethyl acetate extracts of its leaves and stems showed antimicrobial activities.

Objectives To isolate and identify the antimicrobial compounds from I. megalophylla leaves and stems.

Materials and methods The dried leaves (1.7?kg) and stems (3.5?kg) were consecutively extracted with petroleum ether (5?L?×?4), ethyl acetate (5?L?×?3) and ethanol (5?L?×?4) under reflux conditions. The ethyl acetate extract was subjected to an antimicrobial assay guided isolation with Candida albicans and Streptococcus mutans. Compounds 1–10 were identified by ¹H NMR, ¹³C NMR and EI-MS. Minimal lethal concentration (MLC) against C. albicans and Streptococcus spp. was determined using a broth microdilution method for 48 and 24?h, respectively.

Results and discussion On the basis of the antimicrobial assay guided isolation, 10 known compounds, including vanillic acid (1), syringic acid (2), 4-hydroxy benzaldehyde (3), scopoletin (4), loliolide (5), syringaldehyde (6), sinapaldehyde (7), coniferaldehyde (8), syringaresinol (9) and 2,2′-dithiodipyridine (10), were identified. Compounds 1–5 were purified from the ethyl acetate extract of the leaves, while 6–9 and 10 were from the ethyl acetate and ethanol extracts of the stems, respectively. Among these isolates, 10 showed the strongest antibacterial activities against S. mutans and Streptococcus mitis, with minimum inhibitory concentrations (MICs) of 2–4?μg/mL, and MLC of 4?μg/mL, as well as having a weak antifungal activity against C. albicans (MIC of 125?μg/mL). This is the first report of the antimicrobial activities of 10.