7Beta-oxygenated limonoids from Trichilia elegans ssp. elegans

Five 7beta- and 7alpha-oxygenated obacunone-type limonoids were obtained on reinvestigation of the seeds of Trichilia elegans ssp. elegans: 7-deoxo-7beta-acetoxykihadanins A and B, 7-deoxo-7beta-hydroxykihadanins A and B and 7-deoxo-7alpha-hydroxykihadanin A, the last three being isolated after acetylation procedures as their mono- and/or diacetate derivatives. This is the first report of the natural occurrence of C-7 beta-substituted limonoids without any oxygenated function at C-6. The structures of these compounds have been established on the basis of 1D- and 2D-NMR spectral techniques, ESI-mass spectrum and X-ray crystallographic data.     

Characterization of Limonoids Isolated from the Fruits of Melia toosendan and Their Antifeedant Activity against Pieris rapae

The fruits of Melia toosendan Sieb . et Zucc . (Meliaceae) are a source of bioactive limonoids that can be used as effective pesticides. In this study, two novel limonoids, 6‐acetylsendanal and 6‐ketocinamodiol, were isolated together with fourteen known compounds, namely four protolimonoids, six trichilin‐class limonoids, and four C‐seco limonoids. The structures of the new compounds were determined by extensive spectroscopic analyses (HR‐ESI‐MS, UV, IR, 1D and 2D NMR). The bioassay results revealed that eleven of the extracted limonoids exhibited interesting antifeedant activities against the larvae of Pieris rapae with AFC₅₀ values in the range of 0.11–1.79 mm . Particularly, mesendanin H, with an AFC₅₀ value of 0.11 mm , exhibited a higher activity than the positive control toosendanin. Information on new bioactive limonoids may provide further insight into M. toosendan as a source of bioactive components.     

Phragmalin-type limonoids with NF-κB inhibition from Chukrasia tabularis var. velutina

Chemical investigation on Chukrasia tabularis var. velutina led to the identification of eight new phragmalin-type limonoids (1–8), as well as 20 known analogues. Compounds 1–4 are a rare class of C-15-acyl phragmalin-type limonoids, and particularly compounds 2–4 also possess a δ-lactone ring formed between C-16 and C-30. All the isolates were evaluated for inhibitory effects on NF-κB production, and four of which showed significant inhibitions.     

Three new C-15-isobutyryl 16-norphragmalin-type limonoids from Chukrasia tabularis var. velutina

Three new C-15-isobutyryl 16-norphragmalin-type limonoids, chukvelutins D–F (1–3), were isolated from the stem bark of Chukrasia tabularis var. velutina. Their structures were established on the basis of detailed spectroscopic analysis. Compound 1 possessed a ketonic isobutyryl C-15 substitution previously unreported in phragmalin-type limonoids. Compounds 2 and 3 showed moderate anti-inflammatory activity with IC₅₀ values at 10.01 and 28.54 μM.     

Arabidopsis CYP90B1 catalyses the early C-22 hydroxylation of C27, C28 and C29 sterols

Arabidopsis dwf4 is a brassinosteroid (BR)-deficient mutant, and the DWF4 gene encodes a cytochrome P450, CYP90B1. We report the catalytic activity and substrate specificity of CYP90B1. Recombinant CYP90B1 was produced in Escherichia coli, and CYP90B1 activity was measured in an in vitro assay reconstituted with NADPH-cytochrome P450 reductase. CYP90B1 converted campestanol (CN) to 6-deoxocathasterone, confirming that CYP90B1 is a steroid C-22 hydroxylase. The substrate specificity of CYP90B1 indicated that sterols with a double bond at positions C-5 and C-6 are preferred substrates compared with stanols, which have no double bond at the position. In particular, the catalytic efficiency (k(cat)/K(m)) of CYP90B1 for campesterol (CR) was 325 times greater than that for CN. As CR is more abundant than CN in planta, the results suggest that C-22 hydroxylation of CR before C-5alpha reduction is the main route of BR biosynthetic pathway, which contrasts with the generally accepted route via CN. In addition, CYP90B1 showed C-22 hydroxylation activity toward various C(27-29) sterols. Cholesterol (C27 sterol) is the best substrate, followed by CR (C28 sterol), whereas sitosterol (C29 sterol) is a poor substrate, suggesting that the substrate preference of CYP90B1 may explain the discrepancy between the in planta abundance of C27/C28/C29 sterols and C27/C28/C29 BRs.     

Limonoids with an Oxygen Bridge between C(1) and C(29) from the Seeds of a Krishna Mangrove,Xylocarpus granatum

Ten limonoids, named granatumins L–U ( 1 – 10 , resp.), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum, collected in the estuary of Krishna, Andhra Pradesh. The structures of these compounds were established on the basis of spectroscopic data. The relative configuration of granatumin L ( 1 ) was confirmed by a single‐crystal X‐ray diffraction analysis. Granatumins L–T ( 1 – 9 , resp.) belong to the small group of limonoids with an oxygen bridge between C(1) and C(29), while granatumin U ( 10 ) is a 28‐Me‐oxidized mexicanolide. This is the first report of limonoids with an O‐bridge between C(1) and C(29) from the Indian X. granatum. The pronounced structural diversity of limonoids from this mangrove might originate from environmental factors.     

Four new limonoids from the seeds of Chukrasia tabularis A. Juss.

Two new C-15 enolic acyl phragmalin-type limonoid orthoesters (1-2) which possessed a C-15-propionyl phragmalin skeleton and two new mexicanolide-type limonoids (3-4) were isolated from the ethanol extract of seeds of Chukrasia tabularis A. Juss. Their structures were established on the basis of spectroscopic analyses and electronic circular dichroism (ECD) exciton chirality method. Additionally, all of the compounds were screened against three human tumor cell lines MCF-7, SMMC-7721, and U2OS.     

Thaixylomolins D–F,new limonoids from the Thai true mangrove,Xylocarpus moluccensis

Three new limonoids, named thaixylomolins D–F (1–3), were obtained from the seeds of a Thai true mangrove, Xylocarpus moluccensis. The structures of these compounds were identified by extensive NMR and HR-ESIMS/MS investigations. They are further additions to the small group of phragmalins with a C-30 carbonyl moiety, among which thaixylomolins D–E (1–2) contain a Δ^8,14 double bond, whereas thaixylomolin F (3) possesses conjugated Δ^8,9 and Δ^14,15 double bonds.     

五种新化合物对亚洲玉米螟幼虫生长发育和消化生理的影响(英文)

研究了五个新化合物对亚洲玉米螟 (Ostriniafurnacalis)五龄幼虫的拒食活性以及对其生长发育和中肠蛋白酶活性的影响 ,并与川楝素的作用效果进行了比较。结果表明 ,川楝素以及C19、C2 3 、C2 4、C2 6、C2 8在 5 0 0mg kg浓度下拒食活性分别为 5 1 16 %、5 7 6 1%、4 2 8%、5 1 0 8%、36 73%、5 1 6 7% ,其中C19、C2 4、C2 8拒食活性与川楝素相当。在 2 0mg kg浓度 ,生长发育实验表明C19、C2 6、C2 8具有较好的抑制幼虫生长作用 ,其中C2 8的作用与川楝素相当 ;药剂对中肠蛋白酶的影响结果表明 ,川楝素和C2 8对弱碱性类胰蛋白酶、类胰凝乳蛋白酶表现为激活作用 ,C19、C2 4、C2 6对两种蛋白酶在 2 4h激活 ,4 8h抑制。对相关作用机理进行了探讨。     

Limonoids from the fruits of Melia toosendan

Four (1–4) new and seven known limonoids were isolated from the EtOH extract of the fruits of Melia toosendan. The structures of the new compounds were established on the basis of spectroscopic methods to be 12-O-methyl-1-O-deacetylnimbolinin B (1), 12-O-methy-1-O-tigloyl-1-O-deacetylnimbolinin B (2), 12-O-ethylnimbolinin B (3), and 1-O-cinnamoyl-1-O-debenzoylohchinal (4). Additionally, two new tirucallane-type triterpenoids, named meliasenins S (5) and T (6), were obtained from the same fractions during purification of the limonoids.     

Natural products-based insecticidal agents 11. Synthesis and insecticidal activity of novel 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxin derivatives against Mythimna separata Walker in vivo

In continuation of our program aimed at the discovery and development of natural products-based insecticidal agents, 14 novel 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxin derivatives were stereoselectively semisynthesized from podophyllotoxin, and preliminarily evaluated for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo. Especially compounds 9c' and 9g' exhibited the most promising and pronounced insecticidal activity than toosendanin, a commercial insecticide derived from Melia azedarach at 1mg/mL. Generally, it was preliminarily demonstrated that arylsulfonyloxy groups at the C-2 position of benzyloxy moiety and the length of the side chain on the benzenesulfonyloxy group of 4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxins might be important for the insecticidal activity.     

Structural elucidation of limonoids and steroids from Trichilia connaroides

Six limonoids, trijugins D-H (1-5) and methyl 8alpha-hydroxy-8,30-dihydroangolensate (6), two degraded limonoids, trichiconnarins A and B (7-8), and a pregnane steroid, 3beta,4alpha-dihydroxypregnan-21-one (9), along with the known trijugin C (10) and 3beta,4alpha-dihydroxypregnan-16-one (11) were isolated from twigs and leaves of Trichilia connaroides. Their structures were established on the basis of extensive spectroscopic analysis.     

The Anti-Botulism Triterpenoid Toosendanin Elicits Calcium Increase and Exocytosis in Rat Sensory Neurons

Toosendanin, a triterpenoid from Melia toosendan Sieb et Zucc, has been found before to be an effective anti-botulism agent, with a bi-phasic effect at both motor nerve endings and central synapse: an initial facilitation followed by prolonged depression. Initial facilitation may be due to activation of voltage-dependent calcium channels plus inhibition of potassium channels, but the depression is not fully understood. Toosendanin has no effect on intracellular calcium or secretion in the non-excitable pancreatic acinar cells, ruling out general toosendanin inhibition of exocytosis. In this study, toosendanin effects on sensory neurons isolated from rat nodose ganglia were investigated. It was found that toosendanin stimulated increases in cytosolic calcium and neuronal exocytosis dose dependently. Experiments with membrane potential indicator bis-(1,3-dibutylbarbituric acid)trimethine oxonol found that toosendanin hyperpolarized capsaicin-insensitive but depolarized capsaicin-sensitive neurons; high potassium-induced calcium increase was much smaller in hyperpolarizing neurons than in depolarizing neurons, whereas no difference was found for potassium-induced depolarization in these two types of neurons. In neurons showing spontaneous calcium oscillations, toosendanin increased the oscillatory amplitude but not frequency. Toosendanin-induced calcium increase was decreased in calcium-free buffer, by nifedipine, and by transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. Simultaneous measurements of cytosolic and endoplasmic reticulum (ER) calcium showed an increase in cytosolic but a decrease in ER calcium, indicating that toosendanin triggered ER calcium release. These data together indicate that toosendanin modulates sensory neurons, but had opposite effects on membrane potential depending on the presence or absence of capsaicin receptor/TRPV 1 channel.     

川楝素诱导人胃癌MGC-803细胞凋亡及其机制

目的: 本研究旨在探讨川楝素诱导人胃癌MGC-803细胞凋亡及其机制。方法: 将人胃癌MGC-803细胞分为5组,每组3个复孔,采用氟尿嘧啶(5-FU)和0 nmol/L川楝素(TSN)分别作为阳性对照和阴性对照。其余3组分别加入终浓度为30 nmol/L、50 nmol/L、70 nmol/L的川楝素。川楝素处理细胞48 h后,利用激光共聚焦显微镜观察细胞形态结构变化;流式细胞术检测线粒体膜电位变化;酶标法检测Caspase-3和Caspase-9活性;利用qRT-PCR和Western blot检测凋亡相关基因Bcl-2、Bax、Cyt c和APAF-1 mRNA和蛋白水平。结果: 与0 nmol/L TSN组相比,30 nmol/L、50 nmol/L、70 nmol/L的川楝素作用于人胃癌MGC-803细胞48 h,可见细胞体积缩小,细胞核裂解,部分染色质凝集等形态学变化;Caspase-3和Caspase-9活性升高(P＜0.05);而线粒体膜电位明显下降(P＜ 0.05);Bax、Cyt c和APAF-1 基因mRNA及蛋白表达量显著升高(P＜0.05),Bcl-2 基因mRNA及蛋白表达量显著降低(P＜0.05)。结论: 川楝素通过上调Bax、Cyt c和APAF-1的表达,下调Bcl-2基因表达,增强Caspase-3、Caspase-9活性诱导人胃癌MGC-803细胞凋亡。     

Linckosides A and B, two new neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata

Two new steroid glycosides, named linckosides A and B, were isolated from the Okinawan starfish Linckia laevigata, and their stereostructures were elucidated by spectroscopic methods and chemical derivatization. Each of them possesses two monosaccharide units at C-3 and C-29 of a polyhydroxylated steroid aglycon. These steroid glycosides showed not only notable neuritogenic activity against PC12 cells but also significant synergistic effects on the NGF-induced neuronal differentiation of PC12 cells. Linckoside B showed higher activities than those of linckoside A, though the structural difference is only the kind of a sugar.     

Synthesis and cytotoxic activity of heterocyclic ring-substituted betulinic acid derivatives

A new series of betulinic acid derivatives have been synthesized by introducing heterocyclic ring between C-2 and C-3 positions of betulinic acid. Further modifications were also carried out by reduction of C-20(29) unsaturated bond and substitution of C-28 carboxyl group by ester and amide linkage to enhance the selectivity. Compound 11 resulted in IC(50) of 2.44, 2.5, and 2.7 microg/ml on MIAPaCa, PA-1, and SW620 cancer cell lines, respectively. Compound 38 resulted in IC(50) of 0.67 microg/ml on MIAPaCa cell line.     

Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)

Two new limonoids, trichilinin M ( 1 ) and ohchinin benzoate ( 2 ), along with two known limonoids, 12-hydroxyamoorastatone ( 3 ) and mesendanin H ( 4 ), were isolated from the fruits of Melia azedarach Linn. The structures of new limonoids were determined by analyses of HR-ESI-MS, 1D and 2D NMR (HSQC, HMBC and NOESY) data. All compounds were evaluated against human pancreatic cancer PANC1 cells and the results showed that compounds 3 – 4 exhibited substantial cytotoxic activity ( 3 : IC₅₀=4.55 μM; 4 : IC₅₀=7.54 μM), and compounds 1 – 2 exhibited moderate cytotoxicity ( 1 : IC₅₀=27.06 μM; 2 : IC₅₀=21.17 μM).