Guaianolides from Tricholepis glaberrima

Cynaropicrin and 11,13-dihydrodesacylcynaropicrin were isolated from Tricholepis glaberrima.     

Sesquiterpene lactones and other constituents from Stevia jorullensis

A chemical study of the aerial parts of Stevia jorullensis was carried out as a contribution to the knowledge of the chemistry of the genus Stevia. In this investigation the sesquiterpene lactones 11β,13-dihydrocostunolide (1), 11,13-dihydroreynosin (4), and 1β-hydroxycolartin (5) were isolated for the first time in the genus. Additionally, chlorogenic acid (8), the steroidal compounds β-sitosterol (2), stigmasterol (3), β-sitosteryl glucopyranoside (6), and stigmasteryl glucopyranoside (7) were also isolated. This is the third report of the presence of a 11,13-dihydrogermacranolide and the second of 11,13-dihydroeudesmanolides in the genus Stevia.     

Sesquiterpene lactones from pyrethrum flowers

Three new sesquiterpene lactones of the germacranolide-type [(11R)-11,13-dihydrotatridin-A, (11R)-11,13-dihydrotatridin-B and (11R)-6-O     

Sesquiterpenes and diterpenes from Ambrosia arborescens

Six compounds, eudesm-11(13)-en-4β,9β-diol, 15R,16-dihydroxy-3-oxoisopimar-9(11)-ene, 15S,16-dihydroxy-3-oxoisopimar-9(11)-ene, 1α-hydroxy-7-oxo-iso-anhydrooplopanone, 10α-hydroxy-11,13-dihydro-5-epi-psilostachyin, and 4β-hydroxypseudoguaian-12,6-olide 4-O-β-d-glucopyranoside, together with 12 known sesquiterpenes, were isolated from the leaves of Ambrosia arborescens. Structures were elucidated by 1D and 2D NMR spectroscopy including 1D-TOCSY, DQF-COSY, 2D-ROESY, HSQC, and HMBC experiments, as well as by ESI mass spectrometry. The absolute configuration of the 15,16-diol moiety in 15R,16-dihydroxy-3-oxoisopimar-9(11)-ene and 15S,16-dihydroxy-3-oxoisopimar-9(11)-ene was determined using Snatzke’s method. All compounds were evaluated for antiproliferative activity.     

Synthesis and biological evaluation of amino analogs of Ludartin: Potent and selective cytotoxic agents

Diverse amino analogs of Ludartin, a cytotoxic guaianolide and a position isomer of an anticancer drug, Arglabin were prepared through Michael type addition at its highly active α-methylene-γ-lactone motif. The semisynthetic derivatives were subjected to sulphorhodamine B cytotoxicity assay against a panel of four different human cancer cell lines viz. lung (A-549), leukemia (THP-1), prostate (PC-3) and colon (HCT-116) to look into structure–activity relationship. Few of the analogs displayed potent selective cytotoxicity compared to the parent molecule-Ludartin (1). (11R)-13-(Diethyl amine)-11,13-dihydroludartin (6) and (11R)-13-(piperidine)-11,13-dihydroludartin (10) showed almost same cytotoxicity against leukemia cell lines (THP-1) as that of parent molecule-Ludartin, but were more active against colon (HCT-116) cancer cells. (11R)-13-(Morpholine)-11,13-dihydroludartin (11) displayed selectively better cytotoxicity against Leukemia cancer cells (THP-1) exhibiting IC₅₀ of 2.8 μM. (11R)-13-(6-Nitroindazole)-11,13-dihydroludartin (17) was four times more potent than Ludartin with selective cytotoxic effects against prostate cancer cells (2.2 μM) while as (11R)-13-(6-nitroindazole)-11,13-dihydroludartin (18) exhibited three-fold selective cytotoxicity for Lung (A-549) cancer cell lines exhibiting IC₅₀ of 2.6 μM.     

Sesquiterpene lactones from Algerian Artemisia herba-alba

The phytochemical investigation of the methylene chloride/methanol extract of the aerial parts of Artemisia herba-alba afforded two new natural sesquiterpene lactones 1β,9β-diacetoxyeudesm-3-en-5α,6β,11βH-12,6-olide (1) and 1β,9β-diacetoxyeudesm-4-en-6β,11βH-12,6-olide (2). The structures of the compounds were determined by comprehensive NMR studies, including DEPT, COSY, NOESY, HMQC, HMBC and HRMS.     

黄斑卷蛾雄蛾对性信息素的行为反应

分别在风洞中和田间观察了黄斑卷蛾Acleris fimbriana Thunberg et Becklin雄蛾对合成性信息素三种成分（E11,13-14∶Ald, E11,13-14∶Ac和E11-14∶Ac）及其不同组合的行为反应。在风洞中,主要活性成分E11,13-14∶Ald能引起雄蛾完成从兴奋到搜索释放源的行为反应,但雄蛾对单个组分E11,13-14∶Ac 或 E11-14∶Ac不呈现任何行为反应。当释放源为双组分 E11,13-14∶Ald＋E11,13-14∶Ac （6∶4）或三组分E11,13-14∶Ald＋E11,13-14∶Ac＋E11-14∶Ac（6∶4∶1）时,可以明显增加雄蛾定向飞行和到达释放源的数量。三组分 E11,13-14∶Ald＋E11,13-14∶Ac＋E11-14∶Ac的比例为6∶4∶1时,500 μg剂量效果最好。田间试验结果表明,E11,13-14∶Ald单独使用表现出良好的诱蛾活性,其诱蛾量为活雌蛾的1.9倍,而E11,13-14∶Ac和E11-14∶Ac则不具有诱蛾活性。E11,13-14∶Ac对E11,13-14∶Ald有明显的增效作用,三组分E11,13-14∶Ald＋E11,13-14∶Ac＋E11-14∶Ac（6∶4∶1）诱芯的诱蛾效果最好。     

Chromones from the tubers of Eranthis cilicica and their antioxidant activity

Chemical studies on the constituents of Eranthis cilicica led to isolation of ten chromone derivatives, two of which were previously known. Comprehensive spectroscopic analysis, including extensive 1D and 2D NMR data, and the results of enzymatic hydrolysis allowed the chemical structures of the compounds to be assigned as 8,11-dihydro-5-hydroxy-2,9-dihydroxymethyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 5,7-dihydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 5,7-dihydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 9-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-8,11-dihydro-5,9-dihydroxy-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 8,11-dihydro-5,9-dihydroxy-9-hydroxymethyl-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, and 7-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-4-hydroxy-5H-furo[3,2-g][1]benzopyran-5-one, respectively. The isolated compounds were evaluated for their antioxidant activity.     

New derivatives from the aerial parts of Boerhaavia diffusa L. (Nyctaginaceae)

Boerhaavia diffusa L. is used in the traditional medicine of several Asian countries. The isolation and identification of five new compounds, together with 11 known compounds, from the ethyl acetate extract of the aerial part of B. diffusa grown Vietnam is reported. The structure of the new compounds was established by 1D and 2D NMR spectroscopy, and high resolution ESI-MS analysis. New compounds are two rotenoids: 9,11-dihydroxy-6,10-dimethoxy[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one (boeravinone P, 3) and 3-[2-(β-d-glucopyranosyloxy)-3-hydroxyphenyl]-5-hydroxy-2-hydroxymethyl-7-methoxy-6-methyl-4H-1-benzopyran-4-one (boeravinone Q, 9), an atropisomeric mixture of two rotenoid glycosides (3′,5-dihydroxy-2-hydroxymethyl-7-methoxy-6-methylisoflavone 2′-O-β-d-glucopyranoside, 11), a sesquiterpene lactone (4,10-dihydroxy-8-methoxyguai-7(11)-en-8,12-olide, 5) and a new phenylpropanoid glycoside (boerhaavic acid, 15).     

A novel derivatives of thiazol-4(5H)-one and their activity in the inhibition of 11β-hydroxysteroid dehydrogenase type 1

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes the conversion of inactive cortisone into physiologically active cortisol. Inhibiting the activity of this enzyme plays a key role in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. Therefore, new compounds that are selective inhibitors of this enzyme are constantly being looked for.In this work we present the synthesis of 2-(allylamino)thiazol-4(5H)-one derivatives by the reaction of N-allylthiourea with appropriate α-bromoesters. In the case of using of aliphatic α-bromoesters and α-bromo-β-phenylesters, the reactions were carried out in a basic medium (sodium ethoxide) and the products were isolated with a yield of up to 68%. Derivatives containing spiro systems in which carbon C-5 of the thiazole ring is the linker atom were obtained in the presence of N,N-diisopropylethylamine.Some of the obtained compounds, at a concentration of 10 μM have activity in the inhibition of 11β-HSD1 up to 71%. IC₅₀ value for the most active compound: 2-(allylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one is 2.5 µM. With a high degree of 11β-HSD1 inhibition and a relatively large difference in the inhibition of 11β-HSD1 and 11β-HSD2 activity, this compound appears to be promising and should be subjected to further testing.     

Monoterpenoids from the aerial parts of Aruncus dioicus var. kamtschaticus and their antioxidant and cytotoxic activities

The aerial parts of Aruncus dioicus var. kamtschaticus afforded five new monoterpenoids (1-5): 4-(erythro-6,7-dihydroxy-9-methylpent-8-enyl)furan-2(5H)-one (1, aruncin A), 2-(8-ethoxy-8-methylpropylidene)-5-hydroxy-3,6-dihydro-2H-pyran-4-carboxylic acid (2, aruncin B), 4-(hydroxymethyl)-6-(8-methylprop-7-enyl)-5,6-dihydro-2H-pyran-2-one-11-O-β-d-glucopyranoside (3, aruncide A), (3S,4S,5R,10R)-3-(10-ethoxy-11-hydroxyethyl)-4-(5-hydroxy-7-methylbut-6-enyl)oxetan-2-one-11-O-β-d-glucopyranoside (4, aruncide B), and (3S,4S,5R,7R)-5-(9-methylprop-8-enyl)-1,6-dioxabicyclo[3,2,0]heptan-2-one-7-(hydroxymethyl)-12-O-β-d-glucopyranoside (5, aruncide C). Compound 2 showed potent cytotoxicity against Jurkat T cells with an IC₅₀ value of 17.15 μg/mL. In addition, compounds 7 and 10 exhibited moderate antioxidant activity with IC₅₀ values of 46.3 and 11.7 μM, respectively.     

Design,synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging

Several malignant tumors and fibrotic diseases are associated with PDGFRβ overexpression and excessive signaling, making this receptor attractive for molecular targeting and imaging approaches. A series of benzo[d]imidazole-quinoline derivatives were designed and synthesized to develop radioiodinated compounds as PDGFRβ-specific imaging probes. The structure activity relationship (SAR) evaluation of the designed compounds was performed. Among them, 2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (5a) and 4-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (5d) exhibited a relatively high PDGFRβ-TK inhibitory potency, whereas iodinated 5a derivative 5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (8) exhibited a superior inhibitory potency as PDGFRβ inhibitor than iodinated 5d derivative 4-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (11). Furthermore, [¹²⁵I]8 and [¹²⁵I]11 were synthesized and evaluated for PDGFRβ radioligand ability, both in vitro and in vivo. Cellular uptake experiments showed that [¹²⁵I]8 had a higher uptake in BxPC3-luc cells as PDGFRβ-positive cells than [¹²⁵I]11. Incubation of [¹²⁵I]8 after pretreatment of PDGFRβ ligands significantly reduced the uptake of [¹²⁵I]8. In biodistribution experiments using tumor-bearing mice, [¹²⁵I]8 accumulation in the tumor 1?h postinjection was higher than that of the benzo[d]imidazol-quinoline derivative [¹²⁵I]IIQP, used in our previous research. These results indicate that [¹²⁵I]8 could be a promising PDGFRβ imaging agent. Although its clinical application requires further structural modifications, the results obtained in this research may be useful for the development of PDGFRβ-specific radioligands.     

Sex pheromone analysis and effective attraction of males of the cabbage webworm,Hellula undalis,inhabiting the Mekong Delta of Vietnam

Hellula undalis is a harmful insect pest of green mustard in the Mekong Delta of Vietnam. In order to establish a tool for a sustainable pest control program, the sex pheromone of H. undalis inhabiting the Mekong Delta was examined. GC-EAD and GC–MS analyses of pheromone gland extracts from the virgin females elucidated three new components, (Z)-11-tetradecenyl acetate (Z11-14:OAc), (Z)-11-hexadecenal (Z11-16:Ald), and (11E,13E)-11,13-hexadecadien-1-ol, in addition to the known pheromone component (11E,13E)-11,13-hexadecadienal (E11,E13-16:Ald). Double bond positions of the two monoenyl components were determined by GC–MS analysis of the pheromone extract treated with dimethyl disulfide. On the other hand, GC–MS analysis of the female body extract detected the unsaturated hydrocarbon (3Z,6Z,9Z)-3,6,9-tricosatriene (Z3,Z6,Z9-23:H). Field examinations of their synthetic compounds indicated the significant role of E11,E13-16:Ald as a major component and a clear synergistic effect of the two monoenyl compounds as a minor component. Although the 3:3:7 mixture of Z11-14:OAc, E11-16:Ald, and E11,E13-16:Ald captured the largest number of males among the tested mixtures, the activity was still quite a bit lower than that of virgin females. However, the 3:3:7:1 mixture, which was prepared by adding a small amount of Z3,Z6,Z9-23:H to the 3:3:7 ternary lure, succeeded in attracting males more powerfully than the females did. This strong synergistic effect was not observed when the triene was added to unmixed E11,E13-16:Ald, indicating important roles of not only the triene but also the two monoenyl compounds as natural pheromone components.     

Crystal structure of a new cyclomaltoheptaose hydrate: β-cyclodextrin·7.5H2O

The crystallographic study of a partially hydrated form of cyclomaltoheptaose (β-cyclodextrin, βCD) is reported. C₄₂H₇₀O₃₅·7.5H₂O; space group P2₁ with unit cell constants a = 15.1667(5), b = 10.1850(3), c = 20.9694(7) Å, β = 110.993(2)°; final discrepancy index R = 0.0760 for the 6181 observed reflections and 784 refined parameters. One water molecule is included in the cavity and distributed over two partially occupied positions, the other 6.5 waters distributed over eight positions are located as space-filler between the macrocycles. The crystal structure belongs to the cage-type, like that observed in Form I (βCD·12H₂O; Lindner, K; Saenger, W. Carbohydr. Res. 1982, 99, 103-115) and Form II (βCD·11H₂O; Betzel, C., et al. J. Am. Chem. Soc., 1984, 106, 7545-7567).     

Chemophenetics of Azorean Leontodon taxa (Cichorieae,Asteraceae)

The genera Leontodon s.str. and Hedypnois are so far the only known sources of hydroxyhypocretenolides, a rare subclass of guaianolide type sesquiterpene lactones. In this study the three endemic species from the Azorean Archipelago, L. filii, L. hochstetteri, and L. rigens, were analyzed together with L. hispidus and L. × grassiorum, a hybrid originating from L. hispidus and L. hochstetteri. Flowering heads were analyzed by UHPLC-DAD-MS with regards to their phenolics' profiles, establishing qualitatively identical profiles for all taxa. The following phenolics were detected in flowering heads of all investigated taxa: caffeoyltartaric acid, cichoric acid, chlorogenic acid, 3,5-di-O-caffeoylquinic acid, luteolin, luteolin 7-O-β-d-glucopyranoside, luteolin 4′-O-β-d-glucopyranoside, and luteolin 7-O-β-d-glucuronide.In UHPLC-DAD-MS analyses of the rhizomes, no flavonoids were detected. In rhizomes, caffeoyltartaric acid was only detected in L. hispidus. However, in addition to caffeoylquinic acid derivatives already found in the flowering heads, 1,5-di-O-caffeoylquinic acid, 3,4-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid were detected in rhizomes of all investigated taxa.The chemophenetically most interesting group of hydroxyhypocretenolides was detected in rhizomes of all investigated taxa. 11,13β-Dihydro-14-dihydroxyhypocretenolide was detected in L. filii and L. hochstetteri, while 11,13β-dihydro-14-hydroxyhypocretenolide-β-d-glucopyranoside was present in all Azorean taxa. 1,10-Epoxy-14-hydroxyhypocretenolide-β-d-glucopyranoside and 1,10-epoxy-14-hydroxyhypocretenolide-β-d-glucopyranoside-6′-O-p-hydroxyphenylacetic acid ester were restricted to the Azorean taxa and the hybrid L. × grassiorum, while the dimeric sesquiterpenoid 14-hydroxyhypocretenolide-β-d-glucopyranoside-4′,14″-hydroxyhypocretenoate ester was restricted to L. hispidus and L. × grassiorum.     

Synthesis,anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

11-Beta-Hydroxysteroid dehydrogenase-1(11β-HSD1) inhibitors are one of the emerging classes of molecules to fight against diabetic complications. A novel series of 4-(1-substituted-1H-1,2,3-triazol-4-yl)-1,4-dihydropyridine derivatives were synthesized and evaluated for their anti-diabetic activity. Two compounds showed anti-diabetic activity very effectively. To clarify the mechanism of action of these compounds, the most potent compounds (5g and 5h) of the synthesized analogs were further studied by testing its 11-Beta Hydroxysteroid dehydrogenase-1 inhibitory activity through in vitro enzymatic experiments. The results showed that the 11β-HSD1 inhibitory activity of compounds 5g and 5h was stable and efficient. Molecular docking studies revealed compounds 5g (−9.758) and 5h (−8.495) to have a stable binding patterns to the human 11-Beta-Hydroxysteroid dehydrogenase-1.     

The potential of Cyathus africanus for transformation of terpene substrates

The insecticidal sesquiterpenes cadina-4,10(15)-dien-3-one and aromadendr-1(10)-en-9-one were administered to the fungus Cyathus africanus ATCC 35853. Biotransformation of the former produced (4R)-9α-hydroxycadin-10(15)-en-3-one, while the latter gave 2β-hydroxyaromadendr-1(10)-en-9-one, 2α-hydroxyaromadendr-1(10)-en-9-one and 10α-hydroxy-1β,2β-epoxyaromadendran-9-one. The bioconversion of santonin led to the production of two analogues, 11,13-dihydroxysantonin and the hitherto unreported 8α,13-dihydroxysantonin, while cedrol yielded 3β,8β-dihydroxycedrane and 3α,8β-dihydroxycedrane. Stemod-12-ene, a diterpene, was transformed to 2-oxostemar-13-ene, a hitherto unknown analogue with a rearranged carbon framework. When methyl betulonate, a triterpenoid belonging to the lupane family, was supplied to the fungus 18α-ursane and 18α-oleanane derivatives, namely 19β-hydroxy-3-oxo-18α-oleanan-28-oic acid and 19α-hydroxy-3-oxo-18α-ursan-28-oic acids, were generated. There are no previous reports of fungal transformation of a triterpene in which a skeletal rearrangement occurred. All substrate administration experiments were done in the presence of the terpene cyclase inhibitor chlorocholine chloride (CCC), using the single phase – pulse feed method.     

Phytochemical screening of flavonoids with their antioxidant activities from rapeseed (Brassica napus L.)

Ten flavone compounds, including three new flavonoid glycosides, were isolated from defatted rapeseed, and their protective antioxidant effect on H₂O₂-induced oxidative damage in human umbilical vein endothelial cells (ECV-304) was investigated. Three new flavonoid glycosides were identified as kaempferol-3-O-[(6-O-sinapoyl)-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranoside]-7-O-β-d-glucopyranoside (8), kaempferol-3,7-di-O-β-d-glucopyranoside-4'-O-(6-O-sinapoyl)-β-d-glucopyranoside (9), and kaempferol-3-O-[(3-O-sinapoyl)-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranoside]-7-O-β-d-glucopyranoside (10). The protective effects of all of the isolated compounds on H₂O₂-induced oxidative damage were assessed, and the activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH) were measured. All of compounds had a protective effect on H₂O₂-induced oxidative damage in ECV-304 cells and the presence of a substituted sinapoyl group and its position in the structures were used to elucidate the activity differences.     

Zur biogenese des aza-oxa-spiran-systems der steroidalkaloide vom spirosolan-typ in Solanaceen

5α,6-³H₂-Solacongestidine and 5α,6-³ H₂-(22S)-dihydrosolacongestidine administered to Solanum dulcamara as well as 16-³H₂-(22S: 25R)-22,26-epimino- cholest-5-en-3β-ol (25-isodihydroverazine) and 7α-³H-(22S: 25R)-22,26-epimino-cholest-5-en-3β,16β-diol administered to Solanum laciniatum were converted to coladulcidine and solasodine, respectively. These results are discussed in relation to spirosolane alkaloid biosynthesis.     

Design,synthesis and anti-inflammatory evaluation of novel pyrrolo[2,3-d]pyrimidin derivatives as potent JAK inhibitors

Aiming to develop potent JAK inhibitors, two series of 4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives (8a–8p and 11a–11i) were designed and synthesized by coalescing various N-acylpiperidine motifs with baricitinib. The pharmacological results based on enzymatic and cellular assays identified the optimized compound 11e, which exerted over 90% inhibition rates against JAK1 and JAK2, and displayed the most compelling anti-inflammatory efficacy superior to baricitinib by inhibiting NO generation from LPS-induced RAW264.7 macrophages. Importantly, low cytotoxity of 11e was revealed by the IC₅₀ value of 88.2 μM against normal RAW264.7 cells. The binding mode of 11e with JAK1 and JAK2 identified the essential structural bases in accord with SARs analysis. Furthermore, cellular morphology observation and western blot analysis disclosed the ability of 11e to relieve cells inflammatory damage by significantly down-regulating LPS-induced high expression of JAK1, JAK2, as well as pro cytokine IL-1β. Together, 11e was verified as a promising lead for JAK inhibitors for the treatment of inflammatory diseases.