Cytotoxic ent-kauranoids from Isodon leucophyllus

Two new compounds, baiyecrystals D and E (1, 2), together with eight known analogues, xerophilusin B (4), macrocalin B (5), oridonin (6), rosthorin A (7), lasiocarpanin (8), rabdoternin A (9) and phyllostachysin A (10) and B (11), were isolated from the aerial parts of Isodon leucophyllus. The structures of 1 and 2 and 4-11 were elucidated on the basis of spectroscopic methods, especially the 2D NMR spectral analysis. Compounds 2, 6-8 and 10 were evaluated for their antineoplastic activities in vitro. Among them, lasiocarpanin (8) showed significant inhibitory activities against K562 and Bcap37 cells, with the IC₅₀ values of 0.13 and 1.26 μg mL_-1, respectively, which were lower than those of the positive control.     

Synthesis and cytotoxicity of kaempferol derivatives

In the present study, we developed a simple approach for the structural modifications of kaempferol (1). A new compound, 3,5-dihydroxy-2-(4-hydroxyphenyl)-6,8,8-tris(3-methylbut-2-en-1-yl)-4H-chromene-4,7(8H)-dione (5) together with three known compounds, 8-prenylkaempferol (2), 6-prenylkaempferol (3) and 6,8-diprenylkaempferol (4), were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 (IC₅₀ values were 9.45±0.20μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively) and MCF-7 (IC₅₀ values were 10.08±0.57μM, 10.04±0.23 μM and 2.15±0.20 μM,respectively) breast cancer cells.     

Design,synthesis, and in vitro activity of methylisoxazole/isothiazole amides as BACE1 inhibitors

Based on the structure of compound B51 (IC₅₀ = 37.4 μM), which was discovered as hit in a previous virtual screen, a series of methylisoxazole/isothiazole amide derivatives were designed and synthesized as BACE1 inhibitors. The methoxyphenylpyrimidone fragment of B51 was transformed into a methoxyphenylmethylisoxazole/isothiazole moiety to reduce the molecular weight while retaining the ability to fit into the S₁' and S₂' subpocket of BACE1 as predicted by docking studies. The effects of BACE1 inhibition and the structure-activity relationships were analyzed. Among all 20 designed compounds, 5t exhibited almost 10-fold improved potency (IC₅₀ = 5.33 μM) compared to B51 in the BACE1 inhibition assay. Additionally, it has exhibited “rapid binding, slow dissociation” kinetics in SPR analysis, suggesting a longer inhibitory effect than B51. All acquired methylisoxazole/isothiazole derivatives were small in size and safe to normal cells, which allow them represent a novel scaffold for BACE1 inhibitor design.     

Bioactivity of compounds isolated from the leaves of the Lantana camara Linn plant

Two compounds with different bioactivitieswere isolated from the leaves of the Lantana camara Linn plant. Compound 1wastriterpenoid (Lantadene B)(22β-dimethylacroyloxy-3-oxoolean-12-en-28-oic-acid, C₃₅H₅₂O₅), which was isolatedfrom n-hexane fraction and obtained as white solid (amorphous). Compound 2was glycosideflavonoid (5-hydroxy-6,4′-dimethoxyflavon-7-O-glucopyranose, C₂₃H₂₄O₁₁), which was isolated from ethyl acetate and obtained as pale yellow solid (amorphous). Extraction was performed withmaceration method using methanol solvent. Subsequently, fractionation was carried out using n-hexane and ethyl acetate solvents. Isolation and purification of both fractions were conductedusing chromatography method. The structure of the isolated compounds was determined throughspectralanalyses of ultraviolet (UV), infrared (IR), and nuclear magnetic resonance (¹H NMR and ¹³C NMR), distortionless enhancement by polarization transfer (DEPT), heteronuclear multiple bond connectivity (HMBC), heteronuclear single quantum correlation (HSQC), and H-H COSY (¹H-¹H homonuclear correlatedspectroscopy). The cytotoxic activity of compound 1 was tested against MCF-7 breast cancer cellsin vitro using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), showing very strong cytotoxic activity in inhibiting the growth of MCF-7 breast cancer cells, and the IC₅₀ value was 1.1336 µM. The antioxidant activity of compound 2 was tested using DPPH assay (1,1-diphenyl-2-picrylhydrazyl), showing strong activity in inhibiting free radicals, and its IC₅₀ value was 71.03 mg/L.     

Inhibition of protein tyrosine phosphatase 1B by triterpenes isolated from Potentilla discolor Bge

Seven oleanene triterpenes were isolated from the roots of Potentilla discolor Bge and their structures were identified as3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3β-hydroxyolean-12-en-27-oic acid (4), aceriphyllic acid A (5), aceriphyllic acid A methyl ester (6), and oleanolic acid (7). Compounds 1–7 inhibited protein tyrosine phosphatase 1B (PTP1B) activity, with IC₅₀ values ranging from (7.5±0.5) to (22.7±0.5) μmol/L. Among the isolates, compounds 1, 2, 3 and 7 from thePotentilla discolor Bge were found to exhibit selective PTP1B inhibitory activity.     

Synthesis and anticancer activity study of curcumin-related compounds containing benzyl piperidone

Sixteen curcumin-related compounds containing benzyl piperidonewere synthesized and evaluated for their anticancer activity by the MTT assay towards cultured prostate cancer (PC-3), pancreatic cancer (BxPC-3), colon cancer (HT-29), and lung cancer (H1299) cells. Compounds A1 and B3 exhibited potent growth inhibitory effects againstthese cells in culture. The IC₅₀ values of these compounds were lower than 1 µM in all four cell lines.     

姜黄素衍生物64PH的抗肿瘤作用

目的:探讨姜黄素衍生物64PH的体内外抗肿瘤活性。方法:MTT法检测64PH对小鼠B16黑色素瘤细胞及人HepG2肝癌细胞的体外增殖抑制作用;采用小鼠移植性肿瘤H22观察64PH的体内抑瘤活性,HE染色观察肿瘤血管新生。结果:64PH对B16 的IC₅₀分别为10.30 μg·ml^-1(24 h),3.12 μg·ml^-1(48 h), 2.67 μg·ml^-1(72 h),对HepG2的IC₅₀分别为5.60 μg·ml^-1(24 h),7.60 μg·ml^-1(48 h),5.92 μg·ml^-1(72 h);低剂量(100 mg·kg^-1)、高剂量(300 mg·kg^-1)64PH对小鼠H22的抑瘤率分别为26.1%,33.0%,且可明显抑制小鼠H22肿瘤的血管生成。结论:64PH在体内外均具有较好的抗肿瘤活性。     

Cytotoxic activity of polyacetylenes and polyenes isolated from roots of Echinacea pallida

BACKGROUND AND PURPOSE: The n-hexane extracts of the roots of three medicinally used Echinacea species exhibited cytotoxic activity on human cancer cell lines, with Echinacea pallida found to be the most cytotoxic. Acetylenes are present in E. pallida lipophilic extracts but essentially absent in extracts from the other two species. In the present study, the cytotoxic effects of five compounds, two polyacetylenes (namely, 8-hydroxy-pentadeca-(9E)-ene-11,13-diyn-2-one (1) and pentadeca-(9E)-ene-11,13-diyne-2,8-dione (3)) and three polyenes (namely, 8-hydroxy-pentadeca-(9E,13Z)-dien-11-yn-2-one (2), pentadeca-(9E,13Z)-dien-11-yne-2,8-dione (4) and pentadeca-(8Z,13Z)-dien-11-yn-2-one (5)), isolated from the n-hexane extract of E. pallida roots by bioassay-guided fractionation, were investigated and the potential bioavailability of these compounds in the extract was studied. EXPERIMENTAL APPROACH: Cytotoxic effects were assessed on human pancreatic MIA PaCa-2 and colonic COLO320 cancer cell lines. Cell viability was evaluated by the WST-1 assay and apoptotic cell death by the cytosolic internucleosomal DNA enrichment and the caspase 3/7 activity tests. Caco-2 cell monolayers were used to assess the potential bioavailability of the acetylenes. KEY RESULTS: The five compounds exhibited concentration-dependent cytotoxicity in both cell types, with a greater potency in the colonic cancer cells. Apoptotic cell death was found to be involved in the cytotoxic effect of the most active, compound 5. Compounds 2 and 5 were found to cross the Caco-2 monolayer with apparent permeabilities above 10 x 10(-6) cm s(-1). CONCLUSIONS AND IMPLICATIONS: Compounds isolated from n-hexane extracts of E. pallida roots have a direct cytotoxicity on cancer cells and good potential for absorption in humans when taken orally.     

Lignans from Kadsura angustifolia

A new dibenzocyclooctadiene lignan named angustifolin D (1) together with four known lignans: kadsulignan L (2), kadsulignan N (3), schisantherin P (4) and meso-dihydroguaiaretic acid (5) were isolated from the stems of Kadsura angustifolia. Their structures and stereochemistries were elucidated by spectral studies. Compounds 2 and 5 showed moderate plateletactivating factor (PAF) antagonistic activities with IC₅₀ values of 2.6 × 10^-5 and 4.1 × 10^-5 M, respectively.     

金疮小草化学成分的分离与鉴定

目的对金疮小草的化学成分进行研究。方法采用硅胶吸附柱色谱、ODS柱色谱、制备薄层色谱和半制备型高效液相色谱分离纯化,根据1H-NMR、13C-NMR等谱学数据进行结构鉴定。结果从金疮小草干燥全草的甲醇提取物的乙酸乙酯萃取物中分离得到15个单体化合物,分别鉴定为ajugacumbin A(1)、ajugacumbin B(2)、ajuganipponin B(3)、ajugamarin F4(4)、ajugarin I(5)、ajugamarin A1(6)、ajugamarin A1 chlorhydrin(7)、芹菜素(apigenin,8)、木犀草素(luteolin,9)、金合欢素(acacetin,10)、咖啡酸甲酯(methyl caffeate,11)、4-hydroxy-4-(3-oxo-1-butenyl)-3,5,5-trimethylcyclohex-2-en-1-one(12)、香草酸(vanillic acid,13)、黑麦草内酯(loliolide,14)和(10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic acid(15)。结论其中化合物11和12为首次从筋骨草属中分离得到,化合物7和15为首次从金疮小草中分离得到。     

Synthesis and biological evaluation of α,β-unsaturated carbonyl compounds targeting the NLRP3 inflammasome

A series of α,β-unsaturated ketone derivatives were synthesized, and their anti-inflammatory activity toward NLRP3 inflammasome was evaluated in vitro. Several compounds were identified as anti-inflammatory agents, among which compound A21 exhibited potent anti-inflammatory activity in a dose-dependent manner with an IC₅₀ of 0.95 μM. Moreover, a preliminary structure-activity relationship was also summarized.     

Thromboxane A(2)-mediated Cl(-) secretion induced by platelet-activating factor in isolated rat colon

Thromboxane A₂ is a novel endogenous secretagogue of Cl⁻ secretion in the distal colon. Here, we examined if the Cl⁻ secretion caused by platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is mediated by thromboxane A₂ production using isolated mucosae of the rat colon. Furosemide (100 μM) and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB; 300 μM) completely inhibited PAF (10 μM)-induced increase in short-circuit current (Isc) across the mucosa, indicating that PAF caused a Cl⁻ secretion in the rat colon. A selective thromboxane A₂ receptor antagonist (sodium(E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)-ethylidene]-6,11-dihydrobenz[b,e]oxepine-2-carboxylate monohydrate; KW-3635), and a selective thromboxane synthase inhibitor (sodium 4-[-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate dihydrate; Y-20811) inhibited the PAF-induced Cl⁻ current in a concentration-dependent manner. The IC₅₀ values of KW-3635 and Y-20811 were 2.1 and 0.5 μM, respectively. 30 μM KW-3635 and 1 μM Y-20811 inhibited the PAF response by 92% and 83%, respectively. These inhibitors did not affect the prostaglandin E₂-induced increase in Isc. A 5-lipoxygenase-activating protein inhibitor (3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethyl-propanoic acid sodium; MK-886) (5 μM) did not affect the PAF-induced Cl⁻ current. The present study suggests that the PAF-induced Cl⁻ secretion in the rat colonic mucosa is mainly mediated by a release of thromboxane A₂.     

Angiotensin receptor subtypes in the uterine artery during ovine pregnancy

This study was undertaken to determine if changes in receptor density or affinity could account for the reduced vascular sensitivity to angiotensin II seen during pregnancy. Angiotensin receptor subtypes in the uterine arteries of non-pregnant, pregnant and postpartum ewes were investigated using saturation and competition receptor binding techniques with the specific receptor antagonists, losartan (DuP-753) and PD-123319 (S)1-[[4-(dimethylamino)-3-methylphenyl]-methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid, ditrifluoroacetate, monohydrate). Receptor density and affinity of total angiotensin receptors, as well as the angiotensin AT₁ and AT₂ receptor subtypes in uterine arteries were compared with those in the mesenteric artery and aorta. The uterine artery contains both AT₁ and AT₂ receptor subtypes, whereas the mesenteric artery and aorta contain primarily the AT₁ receptor subtype. In uterine arteries from pregnant sheep, angiotensin receptor density was increased because AT₂ receptors were increased. AT₁ receptor density was not altered. This change was not seen in the aorta. In the uterine artery, receptor affinity for [Sar¹,Ile⁸]angiotensin II decreased in mid-gestation (IC₅₀ 7.7±1.2×10⁻⁹ M) compared with non-pregnant ewes (IC₅₀ 3.0±0.6×10⁻⁹ M, P=0.006), and there was decreased affinity of angiotensin AT₁ receptors for losartan during pregnancy (IC₅₀ 2.8±1.0×10⁻⁴ M) compared with non-pregnant ewes (IC₅₀ 2.2±1.3×10⁻⁶ M, P=0.025). Our results show changes in the density and affinity of the angiotensin receptor subtypes in the uterine artery which could explain its reduced responsiveness to circulating angiotensin II during pregnancy.     

Three new compounds from endophytic fungus Periconia sp. F-31

Three new compounds (1–3), includinga chlorine-containing dihydroisocoumarin pericochlorosin A (1), a chlorinated phenol pericochlorosin B (2) and a decalin derivative pericoannosin G (3), were isolated from endophytic fungus Periconia sp. F-31 of the medicinal plant Annona muricata. The structures and absolute configurations were elucidated by extensive spectroscopic methods and calculated electronic circular dichroism analysis. Compound 2 displayed potent anti-HIV activity with IC₅₀ value of 2.2 μM.     

Design,synthesis and biological evaluation of novel quinoline [4,3-b]chromene derivatives as AChE inhibitors through an efficient one-pot,four-component microwave-mediated reaction

An efficient synthesis of chromeno[4,3-b]quinoline derivatives via one-pot, four-component reaction of 4-hydroxycoumarin, formaldehyde, cyclohexanedione, ammonium ceric nitrate under microwave irradiation was accomplished. The structures of these compounds were unambiguously confirmed by single crystal X-ray diffraction. Furthermore, the anti-AChE activities of these compounds in vitro were investigated at concentrations of 20 μM and 50 μM by using a standard Ellman’s method. The relationship of inhibitory activities and structures of these chromeno [4,3-b]quinolines was also systematically studied. Of all the compounds investigated, 4ag emerged as the most potent AChE inhibitor with IC₅₀ values of 5.63 µM, and it might be used as potent lead for the development anti-AChE agents. Moreover, molecular modelling was conducted to understand the optimal interaction of AChE with these types of compounds.     

Biological investigation of phenyl benzoate,benzophenone, and xanthone compounds

In the present study, we evaluated the antitumor, anti-tyrosinase, anti-pancreatic lipase, antibacterial, antifungal, and anti-α‐glycosidase activities for all or a subset of 20 known compounds. They included 8 phenyl benzoates, 10 benzophenones, and 2 xanthones. Phenyl benzoate compounds 1–8 did not exhibit evident antitumor activity, which was consistent with existing theories. Compounds 16, 17, and 18 exhibited moderate anti-tyrosinase activity. In addition, compounds 11 and 18 exhibited moderate inhibitory activity against Candida albicans, and compound 20 exhibited stronger anti-α-glycosidase activity than quercetin, with an IC₅₀ of approximately 2.45 μM. These results demonstrated that compounds 11, 16–18, and 20 were promising leads for further structural modification.     

Comparison of the effects of dimyristoyl and soya phosphatidylcholine liposomes on human fibroblasts

The in vitro effects of prolonged exposure (8 days) of human skin fibroblasts to several concentrations of extruded dimyristoyl (dm-PC) and soya phosphatidylcholine (soya-PC) liposomes were compared. Prepared liposome suspensions were added to the fibroblast culture medium at phospholipid concentrations of 10, 50, 100, 200, and 300 mu M. Survival curves and values of 50% inhibitory concentration (IC₅₀) and area under the curve (AUC) were used to compare the response of the fibroblasts to the two types of liposomes. The effect of the incorporation of vitamin E in the liposomal preparations also was determined. Fibroblasts showed greater sensitivity toward the soya-PC liposomes (IC₅₀ = 150 mu M) than the dm-PC liposomes (IC₅₀ = 212 mu M). The presence of vitamin E in the soya-PC liposomes led to a 1.9-fold increase in the IC₅₀, while dm-PC liposomes containing vitamin E showed an IC₅₀ that was 1.1 times higher than that shown by control vitamin-free liposomes. Soya-PC liposomes containing vitamin E at a molar ratio of 10:0.5 (phospholipid:vitamin)were best tolerated by the fibroblasts (IC₅₀ > 300 mu M). It would appear that dm-PC liposomes are better tolerated by fibroblasts than those composed of soya-PC. However, the incorporation of vitamin E into the liposomes seems to reverse this effect, and it is the vitamin-containing soya-PC liposomes that are most compatible with the growth of fibroblasts in culture.     

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.     

桐花树根多酚提取物体外α-糖苷酶抑制活性与抗氧化能力

目的:研究桐花树根多酚提取物对α-糖苷酶的抑制作用与抗氧化活性。方法:采用PNPG法测定α-葡萄糖苷酶抑制活性,采用羟基自由基清除体系、DPPH·自由基清除体系、对脂质体过氧化活性测定评价桐花树根多酚的抗氧化活性。结果:桐花树根多酚提取物对α-葡萄糖苷酶有一定的抑制活性,IC₅₀为37.75μg·ml^-1。桐花树根多酚提取物表现出较强的抗氧化性能,清除DPPH的IC₅₀为0.618 mg·ml^-1,清除羟自由基的IC₅₀为0.0002 mg·ml^-1,对脂质体过氧抑制能力的IC₅₀约为0.585 mg·ml^-1。结论:桐花树根多酚提取物具有作为新型α-葡萄糖苷酶抑制剂与抗氧化剂的药用开发价值。     

Chemical constituents from the leaves of Cistus parviflorus

A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds. The structures of the isolated compounds were elucidated as kaempferol 3-O-(3′′,6′′-di-O-E-p-coumaroyl)-β-D-glucopyranoside (1), scopoletin (2),kaempferol 3-O-(3′′-O-E-p-coumaroyl)-β-D-glucopyranoside (3), kaempferol 3-O-(6′′-O-E-p-coumaroyl)-β-D-glucopyranoside (4), kaempferol 3-O-β-D-glucopyranoside (5), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-(6′′-O-E-p-coumaroyl)-β-D-glucopyranoside (6), methyl flavogallonate(7), quercetin 3-O-β-D-glucopyranoside (8), quercetin 3-O-β-D-galactopyranoside (9), hydroquinone (10), arbutin (11), methyl β-glucopyranoside (12), shikimic acid (13), (S)-1,2-propandiol-1-O-β-D-glucopyranoside (14), benzyl-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (15), 2-phenethyl-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (16), corchoionoside C (17), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (18) by the analysis of the MS and NMR spectroscopic data and comparison with the literature. Compounds 1–2, 6–7, 10–12, and 14–16 were isolated from Cistus genus for the first time.