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Abstract Two new compounds, odoratisol E (1) and decurrenal A (2), together with 12 known compounds were isolated from the twig and leaf extracts of Mitrephora wangii HU (Annonaceae). All structures were elucidated by spectroscopic methods. The structure of compound (+)- 6 was also confirmed by X-ray diffraction analysis. The absolute configurations of odoratisol E and decurrenal A were determined by comparison of their electronic circular dichroism (ECD) spectra with those of related known compounds. Most of the isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Compounds 4 and (+)- 6 displayed potent ABTS radical scavenging activity with IC 50 values of 11.9 ± 1.8 and 10.8 ± 1.7 μM, respectively, which is better than that of standard compound, ascorbic acid, (IC 50 = 19.3 ± 0.1 μM). Compound 9 showed moderate DPPH radical scavenging activity with an IC 50 value of 38.7 ± 0.8 μM. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

A new bakuchiol compound Δ 11 -12-hydroxy-12-dimethyl bakuchiol ( 1 ), a new flavanone compound 2( S )-6-methoxy-7- hydroxymethylene-4′-hydroxyl-flavanone ( 8 ), and two new isoflavanone compounds 4′,7-dihydroxy-3′-(6”β-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone ( 9 ) and 4′,7-dihydroxy-3′-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone ( 10 ) together with eight known compounds ( 2–7 , 11 , 12 ) were isolated from the P. corylifolia . Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3 , 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC 50 values ranging from 93.7 ± 1.3 to 96.2 ± 1.1 μM. Compound 1 showed inhibition activity on DGAT1 with IC 50 values 73.4 ± 1.3 μM and inhibition of DGAT2 with IC 50 value 121.1 ± 1.3 μM. [ABSTRACT FROM AUTHOR]

Four new cinnamoyl-phloroglucinols ( 1 – 4 ) were isolated from the leaves of Xanthostemon chrysanthus . Compounds 1 and 2 represent the first example of natural phloroglucinols with an oxazole unit. Their structures were elucidated on the basis of NMR spectroscopic data and single crystal X-ray diffraction. Compound 3 showed moderate cytotoxic activity against MDA-MB-231 and SGC-7901 cells with IC 50 values of 25.26 ± 0.35 μM and 31.2 ± 0.94 μM, respectively. [ABSTRACT FROM AUTHOR]

Seven new N -acylanthranilic acid derivatives ( 1–3 , 4a/4b , 5a/5b ) including two pairs of enantiomers ( 4a/4b and 5a/5b ) were isolated from the leaves of Isatis indigotica Fortune. Their chemical structures were elucidated by extensive spectroscopic data analyses. The absolute configurations of compounds 4a/4b and 5a/5b were determined by comparison of the experimental and calculated ECD spectra. All compounds were tested for their anti-A β 1–42 aggregation activity. As a result, compounds 1 (72.1%), 2 (79.8%) and 5a (81.8%) showed stronger inhibitory activity than the positive control curcumin (67.0%). By the comparison between 5a (81.8%) and 5b (63.1%), it was found that stereochemical configurations may affect A β 1–42 aggregation activity, which was discussed through the molecular docking results of compounds 5a and 5b . [ABSTRACT FROM AUTHOR]

Until recently, (methylthio)phenols as natural products had only been reported from bacteria. Now, four representatives of this class of sulfurous aromatic compounds have been discovered as semiochemicals in the orchid Caladenia crebra , which secures pollination by sexual deception. In this case, field bioassays confirmed that a 10:1 blend of 2-(methylthio)benzene-1,4-diol ( 1 ) and 4-hydroxy-3-(methylthio)benzaldehyde ( 2 ) sexually attracts the male thynnine wasp Campylothynnus flavopictus (Tiphiidae:Thynnineae), the exclusive pollinator of C. crebra . Here we show with field bioassays that another undescribed species of Campylothynnus (sp. A) is strongly sexually attracted to a 1:1 blend of compounds 1 and 2 , which elicits very high attempted copulation rates (88%). We also confirm that this Campylothynnus species is a pollinator of Caladenia attingens subsp. attingens . Chemical analysis of the flowers of this orchid revealed two (methylthio)phenols, compound 2 and 2-(methylthio)phenol ( 3 ), as candidate semiochemicals involved in pollinator attraction. Thus, (methylthio)phenols are likely to be more widely used than presently known. The confirmation of this Campylothynnus as a pollinator of C. attingens subsp. attingens at our study sites was unexpected, since elsewhere this orchid is pollinated by a different thynnine wasp ( Thynnoides sp). In general, sexually deceptive Caladenia only use a single species of pollinator, and as such, this unusual case may offer a tractable study system for understanding the chemical basis of pollinator switching in sexually deceptive orchids. [ABSTRACT FROM AUTHOR]

Macroalgae are a rich source of biologically active chemical diversity for pharmaceutical and agrichemical discovery. However, the ability to understand the complexities of their chemical diversity will dictate whether these natural products have a place in modern discovery paradigms. In this study, we examined the relationship between secondary metabolite production and biological activity for a cohort of 127 macroalgae samples collected from various locations across South Eastern Australia. Approximately 20% of the macroalgae samples showed high levels of chemical diversity and productivity, which also correlated strongly with bioactivity. These “talented” species represent sustainable sources of metabolites that may be readily harvested for large-scale production. At a taxonomic level, significant differences in metabolite production and diversity were observed between Chlorophyta, Rhodophyta and Phaeophyta. For each talented species, the cometabolite pattern was unique to that species, with closely related species within the same genus displaying very different profiles. Despite over 50 years of investigation, we estimate that more than two-thirds of the chemical diversity of macroalgae remains unknown to science. By understanding the physicochemical properties and distribution patterns of metabolites, it is possible to make reasoned judgements about sustainable sourcing of macroalgae for biodiscovery. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the fruits from Trichilia connaroides led to the isolation of four rare 1,2- seco phragmalin-type limonoids ( 1 – 4 ) with C-7/28 δ -lactone ring along with two known triterpenoids ( 5 – 6 ). An oxygen bridge between C-1 and C-2 formed an rare 9- oxa -tricyclo[3.3.2.1 7,10 ]undecane-2-ene moiety in structure of 1 and 2 , and 3 – 4 possessed a bicyclo[5.2.1 4,10 ]decane skeleton. Their structures were established based on extensive spectroscopic methods and their absolute configurations of 1 were confirmed by TDDFT/ECD calculation and comparative analysis. Compounds 5–6 showed moderate inhibitory effects on Hela tumor cell lines with inhibition ratio values of 83.8% and 87.1% at concentration 40 μM, respectively. [ABSTRACT FROM AUTHOR]

Urceola rosea , a plant whose leaves are used as food and for medical purposes, is a climbing liana found in many south-east Asian countries. Main polar compounds are flavonoids (kaempferol and quercetin glycosides) and phenolic acids. As an alternative to the established HPLC method their analysis by capillary electrophoresis is described for the first time. It was possible in < 8 min with a 25 mM sodium tetraborate decahydrate solution with pH 8.5, at a capillary temperature of 40 °C and an applied voltage of 25 kV. Up to five compounds could be quantified in different methanolic U. rosea extracts, which showed to be of variable composition; e.g. the content of total flavonoids ranged from 0.29 to 1.08%. In respect to quantitative results as well as validation parameters (e.g. R 2 ≥ 0.994, recovery rates from 95.5 to 103.6%, inter-day precision ≤ 4.5%) the CE method was well comparable to HPLC. However, in terms of required analysis time and environmental sustainability capillary electrophoresis is definitely advantageous. [ABSTRACT FROM AUTHOR]

Taxifolin is a flavonoid. It has been used as a chemopreventive agent and supplement. It may have some beneficial effects to treat prostate cancer by suppressing androgen production in Leydig cells. The objective of the present study was to study the effects of taxifolin on androgen production of rat Leydig cells isolated from immature testis and some rat and human testosterone biosynthetic enzyme activities. Rat Leydig cells were incubated with 100 μM taxifolin without (basal) or with 10 ng/ml luteinizing hormone (LH), 10 mM 8-bromoadenosine 3′,5′-cyclic monophosphate (8BR), and steroid enzyme substrates (20 μM): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione. The medium concentrations of 5α-androstane-3α, 17β-diol (DIOL) and testosterone were measured. Taxifolin significantly suppressed basal, LH-stimulated, 8BR-stimulated, pregnenolone-mediated, and progesterone-mediated androgen production by Leydig cells. Further study demonstrated that taxifolin inhibited rat 3β-hydroxysteroid dehydrogenase and 17α-hydroxylase/17, 20-lyase with IC 50 values of 14.55 ± 0.013 and 16.75 ± 0.011 μM, respectively. Taxifolin also inhibited these two enzyme activities in human testis with IC 50 value of about 100 μM. Taxifolin was a competitive inhibitor for these two enzymes when steroid substrates were used. In conclusion, taxifolin may have benefits for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Seven new sesquineolignans ( 1 – 7 ) were isolated from the 70% ethanolic extract of the hawthorn seeds. Their structures were established by comprehensive spectroscopic analyses including 1D, 2D NMR, CD and HRESIMS data. The neuroprotective activity of the isolated sesquilignans towards H 2 O 2 -induced damage in human neuroblastoma SH-SY5Y cells was investigated. All of these sesquineolignans exhibited significant neuroprotective activity towards damaged SH-SY5Y cells, compared with the positive control (Trolox). Among them, 6 displayed the most potent neuroprotective ability with the survival rate of 90.74% at the concentration of 50 μM. Moreover, Hoechst 33258 staining and Annexin V/PI analysis proved that 6 could protect damaged SH-SY5Y cells through inhibiting cellular apoptosis. [ABSTRACT FROM AUTHOR]

Baccharis retusa, a medicinal Brazilian plant from Asteraceae, has been used in Brazilian folk medicine to treatment of several illnesses, including parasitic diseases. Bioactivity-guided fractionation of the n-hexane extract from the aerial parts of B. retusa resulted in the isolation and characterization of three active related diterpenes: ent -15β-senecioyl-oxy-kaur-16-en-19-oic acid ( 1 ), ent -kaur-16-en-19-oic ( 2 ) and ent -16-oxo-17-nor-kauran-19-oic ( 3 ) acids. The structures of isolated compounds were defined by spectroscopic analysis, including NMR and HRESIMS. Antitrypanosomal activity of 1–3 was performed against cell-derived trypomastigotes using the colorimetric resazurin assay. The obtained results demonstrated that isolated compounds displayed a reduced toxicity against NCTC cells and were effective against the trypomastigote forms of T. cruzi with IC 50 values of 3.8 μM ( 1 ), 75.3 μM ( 2 ) and 44.2 μM ( 3 ). Additionally, compound 3 displayed activity against amastigote forms of T. cruzi with IC 50 of 83.2 μM. Compound 1 displayed the highest selectivity index (SI) when considered the trypomastigote forms, and its effect in the plasma membrane of parasite was evaluated using the fluorescent probe SYTOX Green. A considerable permeabilization (57%) in the membrane of the parasite was observed when compared to the untreated trypomastigotes. These data demonstrate, for the first time, the antitrypanosomal activity and mechanism of action of 1 and related compounds 2 and 3 , obtained from aerial parts of B. retusa . [ABSTRACT FROM AUTHOR]

Streptochlorin, a small indole alkaloid isolated from marine Streptomyces sp., exhibits a wide range of potent biological activities. An efficient and economic synthetic protocol for streptochlorin has been developed and validated, 4 steps from indole in a total yield of 45%, and further applied for the synthesis of its analogues. Biological testing showed that most of the target compounds exhibited potential antifungal activity in the primary assays, especially compounds 6 , 7 and 9c were the most active ones, representing effective activity against the phytopathogenic fungi screened in preliminary test and might be explored for the study of mode of action in the future. [ABSTRACT FROM AUTHOR]

Chemical investigation of Euphorbia helioscopia resulted in the identification of seven new triterpenes named euphorbatrine A-G ( 1 – 7 ), including two (19 α H)-lupane ( 1 – 2 ) and three (9 β H)-lanostane ( 4 – 6 ), which are very rare metabolites from plants. Their structures were elucidated by extensive spectroscopic analysis, X-ray crystallography and chemical methods. Compounds 5 and 6 triggered apoptosis of Hela −/− cell with EC 50 values of 1.59 ± 0.25 and 26.48 ± 0.78 μM, respectively. [ABSTRACT FROM AUTHOR]

The three new metabolites: thiotagetin B ( 2 ) [( Z )-1″-([2,2′-bithiophen]-5-yl)-8″-chloro-6″,11″-dimethylundeca-6″,10″-dien-2″-yn-9″-one], tagetannin A ( 9 ) [3,4-bis-(galloyl-3,5-dimethyl ether)-( α / β )- d -glucopyranose], and tagetannin B ( 10 ) [2,3-bis-(galloyl-3,5-dimethyl ether)-( α / β )- d -glucopyranose], along with ecliptal (5-formyl- α -terthiophene) ( 1 ), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene ( 3 ), scopoletin ( 4 ), p -hydroxybenzoic acid ( 5 ), protocatechuic acid methyl ester ( 6 ), gallic acid ( 7 ), and patuletin 7-O- β - d -glucoside ( 8 ) were isolated from the aerial parts of Tagetes minuta L. (Asteraceae). Their structures were verified by extensive spectroscopic analyses as well as by comparison with literature data. The isolated compounds were evaluated for their antioxidant and anti-inflammatory activities using DPPH and enzyme-linked immunosorbent assays, respectively. Compounds 5 – 10 possessed the highest antioxidant potential with a scavenging activity (SCA) ≈ 74 to 93% of DPPH radicals. Moreover, 5 – 10 displayed significant anti-inflammatory potential, while 4 showed moderate activity. Compounds 5 – 10 exhibited significant decreases in NFκB p65, TNF-α, and IL-6 levels at all tested concentrations. [ABSTRACT FROM AUTHOR]

Twenty natural stilbenoids ( 1 − 20 ), including seven new stilbenoids ( 2 , 4 – 7 , 19 , 20 ) and thirteen known stilbenoids ( 1 , 3, 8 – 18 ), were isolated from the stem barks of Acanthopanax leucorrhizus , and six modified stilbenoid derivatives ( 1a , 2a , 4a , 4b , 7a and 17a ) were obtained via methylation, demethylation and isopentenylation of the corresponding isolates ( 1 , 2 , 4 , 7 and 17 ). These stilbenoids were structurally characterized by comprehensive analysis of their spectroscopic data and comparison with literature information, and evaluated for their cytotoxic activities against three human tumor cell lines (leukemia HL-60, hepatoma SMMC-7721 and breast carcinoma MCF-7) in vitro by MTT assay. The results showed that compounds 1a , 4a and 4b showed potent selective cytotoxicity against SMMC-7721 ( IC 50 = 10.16 ± 1.95 μM and 9.76 ± 1.32 μM) and MCF-7 ( IC 50 = 10.72 ± 2.78 μM) cell lines. The cytotoxic evaluation of these structurally modified stilbenoid derivatives have led to the establishment of a structure-activity relationship. [ABSTRACT FROM AUTHOR]

Aqueous extracts of the roots of Eurycoma longifolia are traditionally used to improve sexual performance, to treat infertility and other sexual dysfunctions but also to increase muscle strength. Nowadays, many different products are commercially available which are promoted as E. longifolia extracts and claim to possess beneficial aphrodisiac effects. Since such herbal aphrodisiac preparations have been recently the target of fraudulent product counterfeiting and because eurycomanone, one of the main quassinoids of E. longifolia , is suspected to possess toxic effects at higher concentrations, a highly selective HPLC-DAD/ELSD method has been established to analyze commercially available products and extracts of plant material. The presented method was established by the use of a mixture of 27 reference compounds for qualitative issues and fully validated according to the ICH guidelines for the quantification of three quassinoides: laurycolactone A, longilactone, and eurycomanone. The calibration curves of these showed a linearity over a range of 0.05 to 1.0 mg/ml, with a regression coefficient not lower than R 2 = 0.9969. The inter-day and intra-day precision (indicated as relative standard deviation) of the developed method was < 2.9%. The recovery ranged from − 3.3% to + 6.0%. Eight randomly purchased products have been analyzed with this method, but only five of them contained E. longifolia compounds in detectable amounts. The concentration of eurycomanone in these products varied from 0.22 ± 0.002 mg eurycomanone per capsule to 1.84 ± 0.08 mg corresponding to a maximal recommended daily intake of 0.76 ± 0.02 to 31.90 ± 0.21 mg. [ABSTRACT FROM AUTHOR]

A phytochemical and biological investigation of the endemic Mascarene Aloes ( Aloe spp.), including A. tormentorii (Marais) L.E.Newton & G.D.Rowley, A. purpurea Lam, A. macra Haw., A. lomatophylloides Balf.f and A. vera (synonym A. barbadensis Mill.), which are used in the traditional folk medicine of the Mascarene Islands, was initiated. Methanolic extracts of the Aloe s under study were analysed using high resolution LC-UV-MS/MS and compounds belonging to the class of anthraquinones, anthrones, chromones and flavone C -glycosides were detected. The Mascarene Aloe s could be distinguished from A. vera by the absence of 2″- O -feruloylaloesin and 7- O -methylaloeresin. GC–MS analysis of monosaccharides revealed the presence of arabinose, fucose, xylose, mannose and galactose in all the Mascarene Aloe s and in A. vera. The crude extracts of all Aloe s analysed displayed antimicrobial activity against Bacillus cereus, Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa . Only extracts of A. macra were active against P. aeruginosa and Klebsiella pneumoniae , while none of the Aloe extracts inhibited Propionibacterium acnes. A. macra displayed anti-tyrosinase activity, exhibiting 50% inhibition at 0.95 mg/mL, and extracts of A. purpurea (Mauritius) and A. vera displayed activity in a wound healing-scratch assay. In vitro cytotoxicity screening of crude methanolic extracts of the Aloe s, using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) showed that only A. purpurea (Réunion) elicited a modest toxic effect against HL60 cells, with a percentage toxicity of 8.2% ( A. purpurea -Réunion) and none of the Aloe extracts elicited a toxic effect against MRC 5 fibroblast cells at a concentration of 0.1 mg/mL. Mascarene Aloe species possess noteworthy pharmacological attributes associated with their rich phytochemical profiles. [ABSTRACT FROM AUTHOR]

Four new naphthoquinones ( 1 – 4 ), named rhinacanthins S ( 1 ), T ( 2 ), U ( 3 ) and V ( 4 ), together with 13 known naphthoquinones were isolated from the leaf extract of Rhinacanthus nasutus . The structures of isolated compounds were elucidated by spectroscopic methods, especially 1D and 2D NMR spectroscopy and mass spectrometry. Rhinacanthin S ( 1 ) exhibited acetylcholinesterase inhibition activity with a % inhibition value of 48.04 ± 3.25. The known rhinacanthin A ( 5 ) showed cytotoxicity against a MCF-7 cell line with an IC 50 value of 8.79 μM, while rhinacanthin N ( 15 ) was active against the NCI-H187 cell line with an IC 50 = 2.24 μM and Vero cells (IC 50 = 3.00 μM) [ABSTRACT FROM AUTHOR]

Resveratrol, a common polyphenol, has extensive pharmacological activities. Resveratrol inhibits some steroid biosynthetic enzymes, indicating that it may block neurosteroid synthesis. The objective of the present study is to investigate the inhibition of resveratrol on neurosteroidogenic enzymes rat 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RDH2). The IC 50 values of resveratrol on SRD5A1, AKR1C9, and RDH2 were > 100 μM, 0.436 ± 0.070 μM, and 4.889 ± 0.062 μM, respectively. Resveratrol competitively inhibited rat AKR1C9 and RDH2 against steroid substrates. Docking showed that resveratrol bound to the steroid binding pocket of AKR1C9. It exerted a mixed mode on these AKR1C9 and RDH2 against cofactors. In conclusion, resveratrol potently inhibited rat AKR1C9 and RDH2 to regulate local neurosteroid levels. [ABSTRACT FROM AUTHOR]

The present study aimed at the phytochemical and pharmacological investigation of Sideritis montana L. (Lamiaceae). Two new abietane diterpenes [sideritins A ( 1 ) and B ( 2 )] were isolated from the methanol extract of the plant. Six known compounds [pomiferin E ( 3 ), 9α,13α- epi -dioxyabiet-8(14)-en-18-ol ( 4 ), paulownin ( 5 ), 6-methoxysakuranetin ( 6 ), 3-oxo-α-ionol ( 7 ) and 4-allyl-2,6-dimethoxyphenol glucoside ( 8 )] were also obtained from the plant. The structures were determined by means of HREIMS and NMR experiments. The antiproliferative effect of the isolated compounds was investigated on human cancer cell lines (HeLa, SiHa and C33A) at 10 and 30 μM concentrations, using the MTT assay. The results demonstrated that pomiferin E ( 3 ) and 6-methoxysakuranetin ( 6 ) displayed considerable activity [inhibition (%) ± SEM: 46.93 ± 2.35 on HeLa (pomiferin E), and 51.52 ± 2.45 on C33A (6-methoxysakuranetin)] at 30 μM concentration. [ABSTRACT FROM AUTHOR]

Four new labdane diterpenoids, 12 β -hydroxy-15-norlabda-8(17),13(14)-dien-16-oic acid ( 1 ), ( E )-15-ethoxy-15-methoxylabda-8(17),12-dien-16-al ( 2 ), ( E )-15 α -ethoxy-14 α -hydroxylabda-8(17),12-dien-16-olide ( 3 ), and 15-ethoxy-12 β -hydroxylabda-8(17),13(14)-dien-16,15-olide ( 4 ) were isolated from the methanol extract of Curcuma amada rhizomes collected in Myanmar, together with 13 known analogs. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were evaluated for their antiproliferative activities against a small panel of five different human cancer cell lines (A549, human lung cancer; HeLa, human cervical cancer; MCF7, human breast cancer; PANC-1 and PSN-1, human pancreatic cancer). Among the isolates, compounds 2 − 4 , 7 , 8 , 12 , and 17 showed mild antiproliferative activities with IC 50 values ranging from 19.7 to 96.1 μM. ( E )-14-Hydroxy-15-norlabda-8(17),12-dien-16-al ( 11 ) exhibited strong antiproliferative activities selectively against HeLa, PANC-1, and PSN-1 cells, with IC 50 values of 5.88, 1.00, and 3.98 μM, respectively. These potencies were comparable to those of the positive control, 5-fluorouracil. [ABSTRACT FROM AUTHOR]

Five new isocoumarin derivatives, pestalactone A–C ( 1–3 ) and pestapyrone D–E ( 4–5 ), together with two known compounds ( 6–7 ) were isolated from the solid cultures of the endophytic fungus Pestalotiopsis sp. obtained from Photinia frasery . Their structures were mainly determined by extensive spectroscopic analysis, Mo 2 (OCOCH 3 ) 4 -induced electronic circular dichroism (ECD), and ECD calculation. Compounds 1 and 2 were rare isocoumarin derivatives and derived from distinctive polyketide pathways. Compound 3 exhibited potent antifungal activity against Candida glabrata (ATCC 90030) with an MIC 50 value of 3.49 ± 0.21 μg/mL. [ABSTRACT FROM AUTHOR]

A new cycloartane sapogenol and a new cycloartane xyloside were isolated from Astragalus karjaginii BORISS along with thirteen known compounds. The structures of the new compounds were established as 3-oxo-6α,16β,24( S ),25-tetrahydroxycycloartane ( 1 ) and 6- O -β- d -xylopyranosyl-3β,6α,16β,24( S ),25-pentahydroxycycloartane ( 2 ) by 1D- and 2D-NMR experiments as well as ESIMS and HRMS analyses. The presence of the keto function at position 3 was reported for the first time for cyclocanthogenol sapogenin of Astragalus genus. In vitro immunomodulatory effects of the new compounds ( 1 and 2 ) along with the n -BuOH and MeOH extracts of A . karjaginii at two different doses (3 and 6 μg) were tested on human whole blood for in vitro cytokine release (IL-2, IL-17A and IFN-γ) and hemolytic activities. The results confirmed that compound 2 , a monodesmosidic saponin, had the strongest effect on the induction of both IL-2 (6 μg, 6345.41 ± 0.12 pg/mL (× 5), P < 0.001) and a slight effect upon IL-17A (3 μg, 5217.85 ± 0.72 pg/mL, P < 0.05) cytokines compared to the other test compounds and positive controls (AST VII: Astragaloside VII; and QS-21: Quillaja saponin 21). All tested extracts and molecules also induced release of IFN-γ remarkably ranging between 5031.95 ± 0.05 pg/mL, P < 0.001 for MeOH extract (6 μg) and 5877.08 ± 0.06 pg/mL, P < 0.001 for compound 1 (6 μg) compared to QS-21 (6 μg, 5924.87 ± 0.1 pg/mL, P < 0.001). Administration of AST VII and other test compounds did not cause any hemolytic activity, whereas QS-21 resulted a noteworthy hemolysis. [ABSTRACT FROM AUTHOR]

Five new limonoids, named sundarbanxylogranins A-E ( 1 – 5 ), were isolated from the seeds of an Indian mangrove, Xylocarpus granatum , collected from mangrove swamps of the Sundarbans, India. The structures of these limonoids were established by HRESIMS and NMR spectroscopic data. Sundarbanxylogranin A ( 1 ) is a rare limonoid containing a bicyclo[5.2.1]dec-3-en-8-one scaffold as the ring A/B-fused core; whereas sundarbanxylogranin B ( 2 ) is a typical mexicanolide with an 8α, 30α-epoxy ring. Sundarbanxylogranins C-E ( 3 – 5 ), among which the former two possess a 29-OMe group with different orientation, belong to a small group of limonoids containing a C 1 - O -C 29 oxygen bridge. Sundarbanxylogranin B exhibited moderate anti-HIV activity with an IC 50 value of 23.14 ± 1.29 μM and a CC 50 value of 78.45 ± 1.69 μM, respectively. [ABSTRACT FROM AUTHOR]

Cranberry procyanidins and quercetin derivatives are considered possible active compounds against urinary tract infections (UTIs). In this paper a small group (n = 6) of healthy subjects consumed a product containing 360 mg of cranberry extract (42.6% w/w of PAC-A and 14.6% w/w of PAC-B) and 200 mg of quercetin. Urine samples were collected after 2,4,6,8, and 24 h. The changes in antiadhesive properties against urophatogenic E . coli of the urinary output were determined in vitro and modification to urinary metabolome were studied by LC-MS. Significant antiadhesive properties of urine samples were observed, with the greatest effect 6–8 h after oral administration, confirming the possible usefulness of cranberry containing products in urinary tract infections (UTI). Metabolomic analysis revealed that valeric acid and valerolactone derivatives that were detected in 6 and 8 h sample, while 4-hydroxy-5-(phenyl)-valeric acid- O -glucuronide and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone at 6 h and 4-hydroxy-5-(phenyl)-valeric acid- O -sulphate, 3-hydroxyphenyl-valeric acid, 5-(4′-hydroxyphenyl)-gamma-valerolactone-4′- O -glucuronide and 4-hydroxy-5-(3′-hydroxyphenyl)-valeric acid-3′- O -sulphate were the most abundant at 8 h. The present study shows that the antiadhesive properties of urine sample after cranberry consumption are not ascribable to the direct effect of PAC-A, because their levels in urinary output are in the range of ng/mL. On the other hand, significant metabolites that were detected are mainly metabolites of intestinal action on polyphenols and PACs, as well as glucuronidated and sulphated quercetin, suggesting an important role of intestinal modification of phytoconstituents in the cranberry extract mechanism of action. [ABSTRACT FROM AUTHOR]

Daphnauranins A ( 1 ) and B ( 2 ), two sesquiterpenoids were isolated from the roots of Daphne aurantiaca Diels. One is an unprecedented 5/7 oxacycloheptane ring system, the other is a sesquiterpene-lignan complex. Their structures were elucidated by comprehensive spectroscopic methods including MS and NMR. Their absolute configurations were further confirmed by the quantum ECD calculations. Daphnauranins A and B showed anti-insect activities against male fruit fly with anti-feeding rate up to 46.2 ± 7.1 and 44.7 ± 5.4% at 1 mM, respectively. [ABSTRACT FROM AUTHOR]

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8–1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150 g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum , a well-known alkaloid never found in this Aconitum species. [ABSTRACT FROM AUTHOR]

Three propolis samples were collected from different regions of Ecuador (Quito, Guayaquil and Cotacachi) and their methanolic extracts were prepared. Preliminary information supplied by TLC and NMR data, allowed us to define two main types of propolis: Cotacachi propoli sample (CPS), rich in flavonoids and Quito and Guayaquil samples (QPS and GPS) containing triterpenic alcohols and acetyl triterpenes as the main constituents. Two different approaches based on RP-HPLC preparative procedure and NMR structural determination (CPS) and GC–MS analysis (QPS and GPS) were successfully used for the chemical characterization of their major compounds. All three propolis extracts were able to inhibit Leishmania amazonensis growth but propolis sample rich in flavonoids was the most active (IC 50 = 17.1 ± 1.7 μg/mL). In the literature this is the first study on propolis from Ecuador. [ABSTRACT FROM AUTHOR]

A set of PEGylated derivatives of oleanolic and maslinic acids has been semi-synthesised, attaching ethylene glycol, diethylene glycol, triethylene glycol or tetraethylene glycol to the C-28 carboxyl group of these natural triterpenes and some derivatives. Another set of PEGylated derivatives has been semi-synthesised by connecting the same four ethylene glycols to the hydroxyl groups of the A ring of these triterpenic acids, through a carbonate linker, by reaction with trichloromethyl chloroformate. The aqueous solubility of some of these PEGylated derivatives has been compared with that of maslinic acid. The cytotoxic effects of 28 triterpenic PEGylated derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed. The best results have been achieved with the HT29 cell line, and specifically with the oleanolic acid derivatives having ethylene glycol or tetraethylene glycol attached to the C-28 carboxyl group, which are approximately 27-fold more effective than their natural precursor. Eight PEGylated derivatives have been selected to compare the cytotoxicity results in the HT29 cancer-cell line with those of a non-tumour cell line of the same tissue (IEC-18), four of which were less cytotoxic in the non-tumour cell line. These compounds showed apoptotic effects on treated cells, with percentages of total apoptosis between 20% and 53%, relative to control, at 72 h and IC 50 concentration, and between 29% to 62%, relative to control, for the same time and IC 80 concentration. We have also found that with the treatment of these compounds in HT29 cancer cells, cell-cycle arrest occurred in the G0/G1 phase. Finally, we have also studied changes in mitochondrial membrane potential during apoptosis of HT29 cancer cells, and the results suggest an activation of the extrinsic apoptotic pathway for these compounds. [ABSTRACT FROM AUTHOR]

Three new 2-phenylnaphthalene derivatives, cherrevenaphthalenes A–C ( 1–3 ), and a new polyoxygenated cyclohexene derivative, (−)-uvaribonol F ( 4 ) together with six known compounds, 5–10 , were isolated from the stem and root extracts of Uvaria cherrevensis (Annonaceae). The structures of all isolated compounds were elucidated by spectroscopic analysis. The structures of 3 and 4 were further confirmed by single crystal X-ray diffraction methods. Compound 2 exhibited modest antiplasmodial activity against the P. falciparum stains TM4/8.2 and K1CB1 with IC 50 values of 18.8 ± 3.63 and 23.4 ± 4.08 μM, respectively, and weak cytotoxicity to a Vero cell line. Furthermore, compound 4 displayed cytotoxic activity against a KB cell line with an IC 50 value of 22.1 ± 0.42 μM but was non-cytotoxic to the Vero cell line. Compound 5 revealed stronger cytotoxicity towards the KB cell line, with an IC 50 value of 5.05 ± 0.86 μM and was nearly equally cytotoxic to the Vero cell line. [ABSTRACT FROM AUTHOR]

Four new bi-phenylethylchromones ( 1 – 4 ) were isolated from the EtOAc extract of artificial agarwood induced by holing method originating from Aquilaria sinensis (Lour.) Gilg. The structures of new compounds were unambiguously elucidated by one- and two-dimensional NMR and HRESIMS measurements, and the absolute configuration was determined by analysis of circular dichroism (CD) spectra. All compounds were tested for acetylcholinesterase (AChE) inhibitory activity using modified Ellman's colorimetric method and α -glucosidase inhibitory activity using PNPG method. Compounds 2 – 4 exhibited different levels of inhibitory activity against AChE with the inhibition ratios in the range of 10–45%. However, none of the compounds was active against the α -glucosidase. [ABSTRACT FROM AUTHOR]

Bakuchicin is a furanocoumarin isolated from the seeds of Psoralea corylifolia , which is used in oriental medicine. However, limited information on the pharmacokinetics of bakuchicin is available and in addition, no determined method has been devised to quantify bakuchicin levels in the plasma. In the present study, we developed and validated a quantification method using liquid chromatography (LC) coupled with tandem mass spectrometry (LC-MS/MS), which was applied to a pharmacokinetic investigation in mouse plasma. LC was performed using an ACE 5 C18 column, and a mixture of acetonitrile and water containing 0.1% formic acid was used as the mobile phase at a flow rate of 220 μL/min. Bakuchicin transition ions in multiple reaction-monitoring modes using positive ionization were observed at m / z 187.0 to m / z 131.0. Bakuchicin and the internal standard (reserpine) had retention times of 4.5 and 4.3 min, respectively. Acceptable linearity (r 2 = 0.996) was observed over the concentration range of 20–1000 ng/mL, with a lower quantification limit of 20 ng/mL in mouse plasma. This method was successfully applied to determine the pharmacokinetic parameters of bakuchicin in mouse plasma and showed that the bioavailability of bakuchicin was 58.3% at 5 mg/kg oral administration. [ABSTRACT FROM AUTHOR]

A series of novel β -elemene isopropanolamine derivatives were synthesized and evaluated for their antitumor activity. The results indicated that all of the compounds showed stronger antiproliferative activities than β -elemene as well as improved aqueous solubility. In particular dimer 6q showed the strongest cytotoxicity against four tumor cell lines (SGC-7901, HeLa, U87 and A549) with IC 50 values ranging from 4.37 to 10.20 μM. Moreover, combination of 6q with cisplatin exhibited a synergistic effect on these cell lines with IC 50 values ranging from 1.21 to 2.94 μM, and reversed the resistance of A549/DPP cells with an IC 50 value of 2.52 μM. The mechanism study revealed that 6q caused cell cycle arrest at the G2 phase and induced apoptosis of SGC-7901 cells through a mitochondrial-dependent apoptotic pathway. Further in vivo study in H22 liver cancer xenograft mouse model validated the antitumor activity of 6q with a tumor inhibitory ratio (TIR) of 60.3%, which was higher than that of β -elemene (TIR, 49.1%) at a dose of 60 mg/kg. Altogether, the potent antitumor activity of 6q in vitro and in vivo warranted further preclinical investigation for potential anticancer chemotherapy. [ABSTRACT FROM AUTHOR]

Ganoderma tsugae is a medicinal mushroom. In a continual study on the bioactive constituents of this fungus, a new lanostanoid, 3 β -acetoxy-16 α -hydroxy-24ξ-methyl-5α-lanosta-8,25-dien-21-oic acid, named tsugaric acid F ( 1 ) and a novel palmitamide, N -(3′ α ,4′ β -dihydroxy-2′ β -(hydroxymethyl)-1′ β -(cyclobutyl)palmitamide ( 2 ) were isolated and characterized from the fruit bodies of G. tsugae , and three novel seco -lanostanoids, 3,4- seco -8α,9α-epoxy-5 α -lanosta-21-oic acid 3,4 lactone ( 5 ), 3,4- seco -5 β -lanosta-7,9(11),4(29)-trien-3,21-dioic acid-3-methyl ester ( 6 ), 3,4- seco -5 β -lanosta-7,9(11),4(29)-trien-3,21-dioic acid ( 7 ), and a known compound, 3-oxo-5α-lanosta-8-en-21-oic acid ( 4 ) were prepared from 3 . The structures of new compounds, 1 , 2 , 5 – 7 were determined by spectroscopic methods. Compounds 1 and 4 showed inhibitory effects on xanthine oxidase (XO) with an IC 50 values of 313.3 ± 80.0 and 43.9 ± 29.9 μM, respectively when 7 exhibited potent inhibitory effect on superoxide anion generation in rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB) with an IC 50 values of 1.3 ± 0.2 μM. Compounds 4 – 7 showed weak cytotoxic activities against PC3 cells. These results indicated that 4 and 7 may be used as cancer chemopreventive agents. [ABSTRACT FROM AUTHOR]

A novel tetralignan, tatarinan T ( 1 ) with the rare C8-C7′ linkage pattern, along with a known monolignan ( 2 ) were isolated from the roots of Acorus tatarinowii Schott. Their chemical structures were elucidated on the basis of NMR and X-ray diffraction analysis. We evaluated the protective effects of two rare lignans against β-amyloid toxicity by using CL4176 transgenic C. elegans model for the first time, and found that they significantly delayed paralysis of worms at the concentration of 100 μM. Compound 2 exhibited the more potential protective effect against β-amyloid toxicity, its value of PT 50 extended up to 62.3% at 100 μM compared with control, especially, it still has 30.8% extension at 10 μM. [ABSTRACT FROM AUTHOR]

Extracts of Chlorophora regia are frequently used in Ghana in traditional medicine. There is, however, no reported data on the chemical composition of the plant. Comprehensive phytochemical investigation of the stem bark of C. regia resulted in the isolation of three new prenylated 2-arylbenzofuran derivatives, regiafuran A–C ( 1–3 ), and one new prenylated flavonol ( 4 ), together with fifteen known compounds ( 5–19 ). Their structures were elucidated by combined spectroscopic analysis of their NMR and HRESI-MS n data. Compounds 1, 2, 5, 9 and 15 exhibited remarkable free radical scavenging properties with IC 50 values of 1.9 μg/ml, 2.4 μg/ml, 2.2 μg/ml, 2.1 μg/ml and 1.8 μg/ml, respectively, compared to the standard trolox (IC 50 1.1 μg/ml). The isolated compounds did not, however, show any anti-inflammatory potential when tested using a PGE 2 (prostaglandin E 2 ) competitive enzyme immunoassay. [ABSTRACT FROM AUTHOR]

Bioassay-guided fractionation of the 60% ethanol extract of the stems of Calophyllum membranaceum using the RXR α transcription activation assay led to the isolation of two new chromanones, calopolyanic acid methyl ester ( 1 ) and isopinetoric acid methyl ester ( 2 ), two new xanthones, calophylixanthones A–B ( 3 – 4 ), and one new C-glycoside, calophymembranside C ( 5 ), along with 13 known compounds. Their structures were elucidated on the basis of extensive spectroscopic data. Compounds 5 , 11 and 18 showed transcriptional inhibitory activity of RXR α with 50% inhibitory concentration (IC 50 ) values of 29.95 ± 1.08, 31.06 ± 9.02, and 25.88 ± 1.62 μM, respectively. [ABSTRACT FROM AUTHOR]

Three unreported sesquiterpenes possessing two new skeletons, tabasesquiterpenes A–C ( 1 – 3 ), together with three known sesquiterpenes ( 3 – 6 ) were isolated from the leaves of Nicotiana tabacum . Their structures were determined mainly by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1 – 6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 exhibited high anti-TMV activity with inhibition rate of 35.2%, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 20.5–28.6%. [ABSTRACT FROM AUTHOR]

The methanolic extract and its subfractions from red peony root, the dried roots of Paeonia lactiflora Pallas showed potent antiallergic effects, as inhibition of immunoglobulin E (IgE)-mediated degranulation in rat basophil leukemia (RBL)-2H3 cells. Bioassay-guided fractionation led to the isolation of 16 monoterpene derivatives, including 3 new compounds, paeoniflorol ( 1 ), 4′-hydroxypaeoniflorigenone ( 2 ) and 4- epi -albiflorin ( 3 ), together with 13 known ones ( 4–16 ). The chemical structures of the new compounds were elucidated on the basis of spectroscopic and chemical evidences. Among the isolated monoterpene derivatives, nine compounds showed potent anti-allergic effects and compound 1 was the most effective. A primary structure-activity relationship of monoterpene derivatives was discussed. [ABSTRACT FROM AUTHOR]

Five new compounds ( 1 – 5 ), including three limonoids, one diterpenoid, and one phytosterol, along with four known limonoids ( 6 – 9 ), were isolated from the ethanolic extracts of whole plants of Munronia henryi . Their structures were elucidated by extensive spectroscopic analysis. In addition, the anti-tobacco mosaic virus (TMV) activities of all the isolated compounds were evaluated by the conventional half-leaf and leaf-disk methods along with Western blot analysis. Most of the tested compounds showed strong antiviral activities, with IC 50 values in the range of 14.8–34.0 μg/mL, compared with ningnanmycin as a positive control (IC 50 = 44.6 μg/mL), and their preliminary structure-activity relationships were also discussed. [ABSTRACT FROM AUTHOR]

Three new alkaloids, liparis alkaloid A ( 1 ), B ( 2 ), C ( 3 ), and three new phenolic glycosides, liparis glycoside H ( 4 ), I ( 5 ), J ( 6 ), together with three known phenolic glycosides ( 7–9 ) were isolated from the whole plant of Liparis odorata . Their structures were characterized on the basis of extensive 1D-, 2D-NMR and HR-ESI-MS experiments. In addition, compounds 1 – 3 revealed hypolipidemic effects in the in vitro bioassays, and the ability to inhibit LPS-induced NO production of these isolated phenolic glycosides ( 4 – 9 ) was also evaluated. [ABSTRACT FROM AUTHOR]

Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A ( 1 ), 17- epi -rauvovertine A ( 2 ), rauvovertine B ( 3 ), 17- epi -rauvovertine B ( 4 ), and rauvovertine C ( 5 ) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata . Compounds 1 / 2 and 3 / 4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1 – 5 were established by spectroscopic analysis and with the aid of molecular modeling. The new alkaloids were evaluated for their cytotoxicity in vitro against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines. [ABSTRACT FROM AUTHOR]

Two new ent -kaurane diterpene glycosides; 12α-(β- d -glucopyranosyloxy)-7β-hydroxykaurenolide ( 1 ) and 7β-(β- d -glucopyranosyloxy)-12α-hydroxykaurenolide ( 2 ), a new steroid; (24 S )-stigmasta-7,22 E ,25-trien-3-one ( 12 ), and known compounds ( 3 – 11 , 13 – 14 ) were isolated from zucchini ( Cucurbita pepo L.) seeds. The absolute structures of 1 and 2 were determined by acid hydrolysis and application of a modified Moscher's method. Furthermore, isolated compounds ( 1 – 14 ), and a derivative, 1a , were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. [ABSTRACT FROM AUTHOR]

A chemical investigation of callus cultures of Dysosma versipellis led to the isolation of five new flavonol dimers, dysoverines A − E ( 1 − 5 ), together with 12 known compounds ( 6 − 17 ). The structures of new compounds were determined by the extensive spectroscopic data analyses. The biosynthetic pathway of the new compounds was proposed to involve O -methylation, prenylation, and Diels–Alder cycloaddition, which successively occurred in cultured plant cells. Compounds 1 − 17 exhibited in vitro neuraminidase inhibitory activities with the IC 50 values of 31.0 − 93.9 μM. [ABSTRACT FROM AUTHOR]

The flower of Edgeworthia gardneri is consumed in beverages in Tibet and has potential health benefits for diabetes. As a part of our continuous studies on dietary supplements for diabetes, two monomers, five dimers and one trimer of coumarins were isolated from the flowers of E. gardneri . One dimer was a new compound ( 1 ) and its structure was determined by spectroscopic methods, including multiple NMR techniques and mass spectrometry. The inhibitory activities of all coumarins against α-amylase and α-glucosidase were evaluated. Compound 4 displayed potent inhibitory effect on both α-amylase and α-glucosidase, with an IC 50 of 90 and 86 μg/mL, respectively. The IC 50 of compound 3 against α-glucosidase was 18.7 μg/mL, and its inhibition mode was noncompetitive. Based on the fluorescence analysis, the binding constant and the number of binding sites of compound 3 were calculated as 2.05 × 10 5 and 1.24, respectively. Furthermore, the interaction between compound 3 and α-glucosidase was a spontaneous process that was driven mainly by hydrophobic force. This study could facilitate the utilization of E gardneri as functional food ingredient. [ABSTRACT FROM AUTHOR]

The two new acylphloroglucinol derivatives, methylene-bis-aspidinol AB (1) and mallopposinol (2), together with the nine known compounds, aspidinol B (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of Mallotus oppositifolius . Their structures were elucidated by spectral analysis including MS, 1D and 2D-NMR spectroscopy. In vitro trypanocidal and antileishmanial activities of compounds 1–9 were evaluated. Mallopposinol (2) and aspidinol B (3) displayed weak antileishmanial activities against Leishmania donovani promastigotes, with EC 50 values of 21.3 and 38.8 μM, respectively. Only the methylene-bis-aspidinol (4) exhibited trypanocidal activity against Trypanosoma brucei brucei trypomastigotes (LC 100 = 0.8 μM) similar to the reference drug pentamidine (LC 100 = 0.4 μM). [ABSTRACT FROM AUTHOR]

Three new glucaric acids, namely 2-feruloyl-4-syringoyl or 5-feruloyl-3-syringoyl glucaric acid ( 1 ), 2-syringoyl-4-feruloyl or 5-syringoyl-3-feruloyl glucaric acid ( 2 ), and 3-feruloyl-4-syringoyl or 4-feruloyl-3-syringoyl glucaric acid ( 3 ), were isolated from Leonurus japonicus Houtt. Their structures were elucidated by detailed spectroscopic means including UV, IR, HR-ESI-MS, 1D and 2D NMR data spectra. The bioactive assays of compounds 1 – 3 against hepatoprotection activity were determined. The result suggested that compound 2 exhibited a moderate hepatoprotection activity and the cell survival rate was 74% (10 − 5 mol/L), using bicyclol (survival rate: 66%, 10 − 5 mol/L) as a positive control. Furthermore, compounds 1 – 3 were evaluated cytotoxic activities in vitro using HCT-8, Bel-7402, BGC-823, A-549, and A2780 model and the results exhibited no obvious cytotoxicity activity. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a Mannich base derivative of baicalein (BA) isolated from Scutellaria baicalensis , as a novel selective CDK1 inhibitor. 12 metabolites of BA-j in the monkey urine were identified by LC–MS–MS and 1 H NMR. The major metabolic pathways of BA-j, by capturing oxygen free radicals ( . O 2 − ) and releasing peroxides (H 2 O 2 ), are degraded into active intermediate metabolite dihydroflavonol, then into main metabolite M179 by Shiff reaction, second metabolite M264 by sulfation, trace amount of metabolite M559 by glucuronidation UGT1A9, and without metabolism by CYP3A4. The metabolic process of BA-j by regulating intracellular reactive oxygen species (ROS) was related with BA-j selectively inducing apoptosis in cancer cells. Pharmacokinetics of 10 mg/kg oral BA-j in monkey by HPLC-UV was best fitted to a two-compartment open model, with t 1/2 ( β ) of 4.2 h, C max 25.4 μM at 2 h, and V d 12.6 L, meaning the drug distributing widely in body fluids with no special selectivity to certain tissues, and being able to permeate through the blood–brain barrier. The protein binding rate of BA-j was 91.8%. BA-j has excellent druggability for oral administration or injection, and it may be developed into a novel anti-cancer drug as a selective CDK1 inhibitor. [ABSTRACT FROM AUTHOR]

Chemical investigation of Gynandriris sisyrinchium (L.) Parl growing in Jordan resulted in the isolation and characterization of a total of twelve compounds two of which are reported here for the first time in nature. These new compounds included the isoflavones; 3′-methyl tenuifone ( 2 ) and gynandrinone ( 5 ). In addition, ten known compounds including; β-sitosterol ( 1 ), 7,3′-dimethoxy-5,6,4′-trihydroxyisoflavone ( 3 ), iristectorigenin ( 4 ), hispidulin ( 6 ), galangustin ( 7 ), 6-hydroxybiochanin A ( 8 ), ursolic acid ( 9 ), ladanetin ( 10 ), 4′-O-methylgenistein ( 11 ) and β-sitosterol glucoside ( 12 ) are also reported here for the first time from G. sisyrinchium . The isolated compounds were characterized by different spectroscopic methods including NMR (1D and 2D), UV, IR and MS (HRESIMS and EIMS). The antioxidant and cytotoxic activities of isoflavones 2 , 3 and 5 were investigated. Compound 3 showed the highest antioxidant activity (IC 50 = 17.3 μg/mL), as compared to compounds 5 and 2 (IC 50 = 26.7 and 51.7 μg/mL, respectively). The cytotoxic activity against the human promyelocytic leukemia HL-60 cells revealed that compound 2 was the most active (40 μM). The results indicate that the cytotoxicity of compound 2 is mediated by apoptosis. [ABSTRACT FROM AUTHOR]

Five new triterpenoid saponins, heinsiagenin A 3- O- [ α - l -rhamnopyranosyl-(1→2)- β - d -glucopyranosyl-(1→2)]- β - d -glucopyranoside ( 1 ), heinsiagenin A 3- O -[ α - l -rhamnopyranosyl-(1→2) -β- d -glucopyranosyl - (1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 2 ), 2 α -hydroxyheinsiagenin A 3- O -[ α - l -rhamnopyranosyl-(1→2)- β - d -glucopyranosyl-(1→2)]- β - d -glucopyranoside ( 3 ), 2 α -hydroxyheinsiagenin A 3- O -[ β - d -glucopyranosyl-(1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 4 ) and N -(2 S , 3 R , 4 R -3-methyl-4-pentanolid-2-yl)-18-hydroxylanosta-8 (9), 22 E , 24 E -trien-27-amide-3- O -[ α - l -rhamnopyranosyl-(1→2) -β- d -glucopyranosyl - (1→2)]-[ β - d -glucopyranosyl-(1→4)]- β - d -glucopyranoside ( 5 ) were isolated from the aerial parts of Mussaenda luteola Delile (Rubiaceae). Structural elucidation was based on the analysis of spectroscopic data (1D and 2D NMR) and HR-ESI-MS. Compound 1 showed potent antitrypanosomal activity with an IC 50 value of 8.80 μM. Compounds 2–4 showed highly potent antitrypanosomal activity with IC 50 values ranging between (2.57–2.84 μM) and IC 90 values ranging between (3.36–4.35 μM), which are 5 fold greater than the positive control DFMO (IC 50 and IC 90 values of 13.06 and 28.99 μM, respectively). Compounds 1 and 2 showed moderate affinity to μ-opioid receptors with K i values of 9.936 μM and 0.872 μM, respectively compared to a K i value of 1.958 nM for the positive control, naloxone HCl. [ABSTRACT FROM AUTHOR]