Two polymethoxylated flavonoids with antioxidant activities and a rearranged clerodane diterpenoid from the leaf exudates of Microglossa pyrifolia

Three novel compounds; two polymethoxylated flavonoids, 5,7,4′-trihydroxy-3,8,3′,5′-tetramethoxyflavone (1), 5,7,3′-trihydroxy-3,8,4′,5′-trimethoxyflavone (2), and a clerodane diterpenoid; 8-acetoxyisochiliolide lactone (3) were characterized from the leaf exudates of Microglossa pyrifolia. In addition, three known polymethoxylated flavonoids including; 5,7,4′-trihydroxy-3,8,3′-trimethoxyflavone (4), 5,3′4′-trihydroxy-3,7,8-trimethoxyflavone (5), 5,3′4′-trihydroxy-7-methoxyflavanone (6) and a clerodane diterpenoid; 7,8-epoxyisocholiolide lactone (7) were identified. Their structures were determined on the basis of spectroscopic evidence. All the compounds did not exhibit antiplasmodial and antimicrobial activities at 47.6 μg/mL and were not cytotoxic at 5 μg/mL. Compound 6 exhibited modest antileishmanial activity with IC₅₀ value of 13.13 μg/mL with 5 and 7 showing activities with IC₅₀ values of 31.13 and 38.00 μg/mL, respectively, therefore inactive. The flavonoids (quercetin derivatives, 4 and 5) showed similar antioxidant activities, using 2,2-diphenylpicrylhydrazyl (DPPH) assay, with IC₅₀ values of 6.2 ± 0.3 μg/mL for 4 (17.3 μM) and 5 (17.8 μM) respectively. These activities were comparable to that of the standard quercetin (IC₅₀ value of 6.0 ± 0.2 μg/mL (19.9 μM)), irrespective of methylation of the characteristic hydroxyl groups expected to be responsible for activity and additional substitution at C-8 in ring A of the flavonoid ring. These studies revealed that the presence of an hydroxyl group at C-4′ positions and oxygenation at C-3 in flavone skeleton, appears to be necessary for good antioxidant activities as encountered in compounds 1, 4 and 5. Substantial reduction in antioxidant activity was shown by methoxylation of the 4′-OH as observed in compound 2 with an IC₅₀ value of 8.79 ± 0.3 μg/mL (24.4 μM).     

Aspernolides F and G,new butyrolactones from the endophytic fungus Aspergillus terreus

Two new butyrolactones: aspernolides F (6) and G (7), together with three stigmasterol derivatives: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), and stigmasta-4,6,8(14), 22-tetraen-3-one (3), two meroterpenoids: terretonin A (4) and terretonin (5), and a butyrolactone derivative: butyrolactone VI (8) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were determined by spectroscopic means (1D, 2D NMR, and HRESIMS), as well as optical rotation measurement and comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 displayed a potent activity against MRSA and C. neoformans with IC₅₀ values of 0.96 μg/mL and 4.38 μg/mL, respectively compared to ciprofloxacin (IC₅₀ 0.07 μg/mL) and amphotericin B (IC₅₀ 0.34 μg/mL), respectively. While, 6 showed good activity against C. neoformans (IC₅₀ 5.19 μg/mL) and mild activity against MRSA (IC₅₀ 6.39 μg/mL). Moreover, 1 and 2 exhibited very good anti-leishmanial activity towards L. donovani with IC₅₀ values of 4.61 and 6.31 μg/mL, respectively and IC₉₀ values of 6.02 and 16.71 μg/mL, respectively.     

Melanogenesis inhibitory activity of a 7-O-9′-linked neolignan from Alpinia galanga fruit

An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC₅₀ = 7.3 μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9′-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2–15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC₅₀ = 2.5 μM), 1′S-1′-acetoxychavicol acetate (2, 5.0 μM), and 1′S-1′-acetoxyeugenol acetate (3, 5.6 μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1′-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9′-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1′ (IC₅₀ = 1.9 μM) and 2′ (4.5 μM)] and racemic mixtures [(±)-1 (2.2 μM) and (±)-2 (4.4 μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1–3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity.     

A new synthesis and an antiviral assessment of the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin

A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC₅₀ of 1.2 μg/mL in the neutral red assay and 14 μg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21–36 μg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4′,4′-difluoro analog of 3 (that is, 2).     

Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits

Bioassay-guided isolation and purification of the ethyl acetate extract of Moringa oleifera fruits yielded three new phenolic glycosides; 4-[(2′-O-acetyl-α-l-rhamnosyloxy) benzyl]isothiocyanate (1), 4-[(3′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (2), and S-methyl-N-{4-[(α-l-rhamnosyloxy)benzyl]}thiocarbamate (3), together with five known phenolic glycosides (4–8). The structures of the new metabolites were determined on the basis of spectroscopic analyses including 1D- and 2D-NMR and mass spectrometry. The anti-inflammatory activity of isolated compounds was investigated with the lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cell line. It was found that 4-[(2′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (1) possessed potent NO–inhibitory activity with an IC₅₀ value of 1.67 μM, followed by 2 (IC₅₀ = 2.66 μM), 4 (IC₅₀ = 2.71 μM), and 5 (IC₅₀ = 14.4 μM), respectively. Western blots demonstrated these compounds reduced LPS-mediated iNOS expression. In the concentration range of the IC₅₀ values, no significant cytotoxicity was noted. Structure–activity relationships following NO-release indicated: (1) the isothiocyanate group was essential for activity, (2) acetylation of the isothiocyanate derivatives at C-2′ or at C-3′ of rhamnose led to higher activity, (3) un-acetylated isothiocyanate derivatives displayed eight times less activity than the acetylated derivatives, and (4) acetylation of the thiocarbamate derivatives enhanced activity. These data indicate compounds 1, 2, 4 and 5 are responsible for the reported NO-inhibitory effect of Moringa oleifera fruits, and further studies are warranted.     

Isolation,structure, and bioactivities of abiesadines A–Y, 25 new diterpenes from Abies georgei Orr

Twenty-five new (abiesadines A–Y, 1–25) and 29 known (26–54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC₅₀ value of 11.0 μg/mL. In another anti-inflammatory assay against TNFα-triggered NF-κB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC₅₀ = 8.7 μg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7α,18-diol (29) both showed the most significant activity against LOVO cells (IC₅₀ = 9.2 μg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC₅₀ = 10.2 μg/mL).     

Cytotoxic activity of butane type of 1,7-seco-2,7′-cyclolignanes and apoptosis induction by Caspase 9 and 3

All stereoisomers of methoxybutane and fluorobutane type of 1,7-seco-2,7′-cyclolignane were synthesized and cytotoxic activities of these compounds were compared with those of all stereoisomers of butane and butanol type compounds. Both enantiomers of butane type secocyclolignane showed higher cytotoxic activity (IC₅₀ = 16–20 μM) than methoxy type compounds, whereas none was observed for all the stereoisomers of butanol type secocyclolignane, however, (−)-Kadangustin J showed stereospecific cytotoxic activity (IC₅₀ = 47–67 μM). Since (R)-9′-fluoro derivative 23 was most potent (IC₅₀ = 19 μM) among the corresponding fluoro stereoisomers, (R)-9′-alkyl derivatives were synthesized, hydrophobic 9′-heptyl derivative 27 showing highest activity (IC₅₀ = 3.7 μM against HL-60, IC₅₀ = 3.1 μM against HeLa) in this experiment. Apoptosis induction caused by Caspase 3 and 9 for (R)-9′-heptyl derivative 27 was observed in the research on the mechanism. A degradation of DNA into small fragments was also shown by DNA ladder assay.     

Constituents of Leonotis leonurus flowering tops

Phytochemical investigation of flowering tops of Leonotis leonurus, yielded a new diterpene ester, 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecan-1-yl-palmitate along with five known metabolites. The structures of all compounds were determined by spectroscopic methods including 1D- and 2D NMR spectroscopy. All the isolated compounds were evaluated for antimalarial, cytotoxicity and for antimicrobial activities. Antimalarial activity for luteolin 7-O-β-d-glucopyranoside (4) (IC₅₀ = 2.2 μg/mL for the D6 clone and 1.8 μg/mL for the W2 clone) was observed. Chloroquine and artemisinin were used as positive controls which showed IC₅₀ of 0.016 and 0.0048 μg/mL for the D6 clone, respectively, and IC₅₀ of 0.14 and 0.0047 μg/mL for the W2 clone, respectively. None of the compounds were cytotoxic to Vero cells up to a concentration of 4.76 μg/mL.     

Two new anti-HBV lignans from Herpetospermum caudigerum

Two new lignans, named (+)-(7′S, 7″S, 8′R, 8″R)-4, 4′, 4″-trihydroxy-3, 5′, 3″-trimethoxy-7-oxo-8-ene [8-3′, 7′-O-9″, 8′-8″, 9′-O-7″] lignoid (1) and (1S)-4-Hydroxy-3-[2-(4-hydroxy-3-methoxy-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-5-methoxy-benzaldehyde (2), along with five known (3–7) ones, have been isolated from the 95% ethanol extract of the seeds of Herpetospermum caudigerum Wall. The structures of the new compounds, including the absolute configurations, were elucidated by spectroscopic and CD analysis. Compounds 1, 2, and 7 displayed inhibitory activities on HBsAg secretion with IC₅₀ values of 20.5, 0.34, and 4.89 μM, while 1, 2, and 7 displayed inhibitory activities on HBeAg secretion with IC₅₀ values of 3.54, 4.83 × 10⁻⁴, and 8.02 μM, and cytotoxicity on HepG 2.2.15 cells with CC₅₀ values of 12.7, 2.96 × 10⁵, and 11.4 μM, respectively.     

Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin,the prototype of the M4 family of proteinases

A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC₅₀ values ranging from 0.0115 μM (compound 3) to 122,637 μM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC₅₀ = 0.0115 μM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC₅₀ = 0.2477 μM) were found to be the most potent inhibitors.     

Novel oxazolinyl derivatives of pregna-5,17(20)-diene as 17α-hydroxylase/17,20-lyase (CYP17A1) inhibitors

New oxazolinyl derivatives of [17(20)E]-pregna-5,17(20)-diene: 2′-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]methyl}-4′,5′-dihydro-1′,3′-oxazole 1 and 2′-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]methyl}-4′,4′-dimethyl-4′,5′-dihydro-1′,3′-oxazole 2 were evaluated as potential CYP17A1 inhibitors in comparison with 17-(pyridin-3-yl)androsta-5,16-dien-3β-ol 3 (abiraterone). Differential absorption spectra of human recombinant CYP17A1 in the presence of compound 1 (λ_max = 422 nm, λ_min = 386 nm) and compound 2 (λ_max = 416 nm) indicated significant differences in enzyme/inhibitors complexes. CYP17A1 activity was measured using electrochemical methods. Inhibitory activity of compound 1 was comparable with abiraterone 3 (IC₅₀ = 0.9 ± 0.1 μM, and IC₅₀ = 1.3 ± 0.1 μM, for compounds 1 and 3, respectively), while compound 2 was found to be weaker inhibitor (IC₅₀ = 13 ± 1 μM). Docking of aforementioned compounds to CYP17A1 revealed that steroid fragments of compound 1 and abiraterone 3 occupied close positions; oxazoline cycle of compound 1 was coordinated with heme iron similarly to pyridine cycle of abiraterone 3. Configuration of substituents at 17(20) double bond in preferred docked position corresponded to Z-isomers of compounds 1 and 2. Presence of 4′-substituents in oxazoline ring of compound 2 prevents coordination of oxazoline nitrogen with heme iron and worsens its docking score in comparison with compound 1. These data indicate that oxazolinyl derivative of [17(20)E]-pregna-5,17(20)-diene 1 (rather than 4′,4′-dimethyl derivative 2) may be considered as potential CYP17A1 inhibitor and template for development of new compounds affecting growth and proliferation of prostate cancer cells.     

Triterpenes from the roots of Lantana montevidensis with antiprotozoal activity

Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13β-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12β,13β-dihydroxyolean-3-oxo-28-oic acid (2) and 12β,13β,22β-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3β,25β-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19α-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with β-sitosterol (11) and β-sitosterol-3-O-β-d-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC₅₀ values against both organisms of 2.1 μM and compound 10 showed activity against same organisms with IC₅₀ values 8.74 and 8.09 μM, respectively, compared to the positive control ciprofloxacin (IC₅₀ = 0.3 μM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC₅₀ values ranging between (2.54–14.95 μM) and IC₉₀ values ranging between (11.90–19.47 μM), using pentamidine as a control (IC₅₀ values 2.09 ≥ 16.8 μM) and IC₉₀ values ranging between (4.72 ≥ 16.8 μM). These compounds also showed highly potent antitrypanosomal activity with IC₅₀ values ranging between (0.39–7.12 μM) and IC₉₀ values ranging between (1.91–10.51 μM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC₅₀ and IC₉₀values 11.82 and 30.82 μM).     

Synthesis of dammarane-type triterpene derivatives and their ability to inhibit HIV and HCV proteases

We synthesized dammarane-type triterpene derivatives and evaluated their ability to inhibit HIV-1 and HCV proteases to understand their structure–activity relationships. All of the mono- and di-succinyl derivatives (5a–5f) were powerful inhibitors of HIV-1 protease (IC₅₀ < 10 μM). However, only di-succinyl (5e) and 2,3-seco-2,3-dioic acid (3b) derivatives similarly inhibited HCV protease (IC₅₀ < 10 μM). A-nor dammarane-type triterpenes (4a and 4b, IC₅₀ 10.0 and 29.9 μM, respectively) inhibited HIV-1 protease moderately or strongly, but were inactive against HCV protease. All compounds that powerfully inhibited HIV-1 or HCV protease did not appreciably inhibit the general human proteases, renin and trypsin (IC₅₀ > 1000 μM). These findings indicated that the mono-succinyl dammarane type derivatives (5a–5d) selectively inhibited HIV-1 protease and that the di-succinyl (5e, 5f) as well as 2,3-seco-2,3-dioic acid (3b) derivatives preferably inhibited both viral proteases.     

Nigrosphaerin A a new isochromene derivative from the endophytic fungus Nigrospora sphaerica

Nigrosphaerin A, a new isochromene derivative (1), was isolated from the endophytic fungus Nigrospora sphaerica and chemically identified as 3-(3,4-dihydroxyphenyl)-4,6,8-trihydroxy-1H-isochromen-1-one-6-O-β-d-glucopyranoside. In addition nineteen known compounds (2–20) were isolated from the same fungus and chemically identified. Compounds (1–3, 5, and 7–16) were isolated for the first time from this fungus. In vitro antileukemic, antileishmanial, antifungal, antibacterial and antimalarial activities of (1–20) were examined. Compounds 5, 7, 9 and 10 showed good antileukemic activity against HL60 cells with IC₅₀ values of 0.03, 0.39, 0.2 and 0.4 μg/mL, respectively and against K562 cells with IC₅₀ values of 0.35, 0.35, 0.49 and 0.01 μg/mL, respectively. Compounds 3, 4 and 6 showed moderate antileishmanial activity with IC₅₀ values of 30.2, 26.4 and 36.4 μg/ml, respectively. Compound 7 showed moderate antifungal activity against Cryptococcus neoformans with IC₅₀ value of 14.8 μg/mL.     

Constituents of Nelumbo nucifera leaves and their antimalarial and antifungal activity

From the leaves of Nelumbo nucifera (an aquatic plant), one new compound, 24(R)-ethylcholest-6-ene-5α-ol-3-O-β-d-glucopyranoside (1), along with 11 known metabolites (2–12), were isolated and identified by spectroscopic methods including 1D- and 2D NMR. Antifungal activity for (R)-roemerine (3) (IC₅₀/MIC = 4.5/10 μg/mL against Candida albicans) and antimalarial activity for (R)-roemerine (3) and N-methylasimilobine (5) (IC₅₀ = 0.2 and 4.8 μg/mL for the D6 clone, respectively, and 0.4 and 4.8 μg/mL for the W2 clone, respectively) was observed. None of the compounds were cytotoxic to Vero cells up to a concentration of 23.8 μg/mL. NMR data for 10-eicosanol (7) and 7,11,15-trimethyl-2-hexadecanone (10) are presented for the first time. An analysis of the structure–activity relationship shows that the substituents in position C-1 and C-2 of aporphine alkaloids are crucial for the antimalarial activity.     

Studies on the anti-hepatitis C virus activity of newly synthesized tropolone derivatives: Identification of NS3 helicase inhibitors that specifically inhibit subgenomic HCV replication

We synthesized new tropolone derivatives substituted with cyclic amines: piperidine, piperazine or pyrrolidine. The most active anti-helicase compound (IC₅₀ = 3.4 μM), 3,5,7-tri[(4′-methylpiperazin-1′-yl)methyl]tropolone (2), inhibited RNA replication by 50% at 46.9 μM (EC₅₀) and exhibited the lowest cytotoxicity (CC₅₀) >1 mM resulting in a selectivity index (SI = CC₅₀/EC₅₀) >21. The most efficient replication inhibitor, 3,5,7-tri[(4′-methylpiperidin-1′-yl)methyl]tropolone (6), inhibited RNA replication with an EC₅₀ of 32.0 μM and a SI value of 17.4, whereas 3,5,7-tri[(3′-methylpiperidin-1′-yl)methyl]tropolone (7) exhibited a slightly lower activity with an EC₅₀ of 35.6 μM and a SI of 9.8.     

Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp

A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a–m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a–m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC₅₀/24 h = 15 ± 0.14 μM) and 3,4-dichlorophenyl tetrazoles (4d) (IC₅₀/24 h = 26 ± 0.09 μM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC₅₀ = 13 ± 0.04 μM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L.braziliensis than on L. amazonensis.     

Hirtellanines A and B,a pair of isomeric isoflavonoid derivatives from Campylotropis hirtella and their immunosuppressive activities

A pair of isomeric isoflavonoid derivatives, Hirtellanines A (1) and B (2), has been isolated from the roots of Campylotropis hirtella (Franch.) Schindl. and their structures were elucidated on the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques. The in vitro assay showed that Hirtellanine A had strong B lymphocyte suppression activity (IC₅₀: 0.06 μM) and T lymphocyte suppression activity (IC₅₀: 0.92 μM). Hirtellanine B showed moderate B lymphocyte suppression activity (IC₅₀: 3.00 μM) and T lymphocyte suppression activity (IC₅₀: 9.55 μM). Due to the potent immunosuppressive activities and lower cytotoxicity, Hirtellanine A could be a promising lead towards novel immunosuppressive agents.     

Two new diphenyl ethers from Acanthopanax senticosus (Rupr. & Maxim.) Harms with PTP1B inhibitory activity

Bioassay-guided fractionation of an EtOAc-soluble extract of Acanthopanax senticosus (Rupr. & Maxim.) Harms yielded two new diphenyl ethers, 3-[3′-methoxy-4′-(4″-formyl-2″,6″-dimethoxy-phenoxy)-phenyl]-propenal (1) and 3-[3′,5′-dihydroxy-4′-(4″-hydroxymethyl-3″,5″-dimethoxy-phenoxy)-phenyl]-propenal (2), along with eight other known compounds (3–10). The structures of these new ethers were elucidated with spectroscopic and physico-chemical analyses. All of the isolates were evaluated for their in vitro inhibitory activity against PTP1B, VHR and PP1. The new compounds (1 and 2) inhibited PTP1B with IC₅₀ values ranging from 9.2 ± 1.4 to 12.6 ± 1.2 μM.     

Structure–cytotoxic activity relationship of sesquilignan,morinol A

The cytotoxic activities of sesquilignans, (7S,8S,7′R,8′R)- and (7R,8R,7′S,8′S)-morinol A and (7S,8S,7′S,8′S)- and (7R,8R,7′R,8′R)-morinol B were compared, showing no significant difference between stereoisomers (IC₅₀ = 24–35 μM). As a next stage, the effect of substituents at 7, 7′, and 7″-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18 (IC₅₀ = 6–7 μM). In the research on the structure–activity relationship of 7″-position of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18, the most potent compounds were 7,7′,7″-phenyl derivative 18 (IC₅₀ = 6 μM) against HeLa cells. Against HL-60 cells, 7″-(4-nitrophenyl)-7,7′-phenyl derivative 33 and 7″-hexyl-7,7′-phenyl derivative 37 (IC₅₀ = 5 μM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7′R,8′R)-morinol A. It was also confirmed that the 7′-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.