Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate,a muscarinic receptor antagonist with anti-inflammatory activity

The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM₃R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.     

Lignan glycosides from the Rhizomes of Smilax trinervula and their Biological activities

Phytochemical investigation of the rhizomes of Smilax trinervula led to isolation and structure elucidation of eight lignan glycosides, including five new lignans, namely, (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4′-O-β-d-glucopyranoside (1), (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4-O-β-d- glucopyranoside (2) (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-4′, 7-epoxy-8, 5′-neolignan 9′-O-β-d-glucopyranoside (3), (7R, 8R)-4, 9, 9′-trihydroxy-3, 5-dimethoxy-7.O.4′, 8.O.3′- neolignan 9′-O-β-d-glucopyranoside (4), and (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-8, 4′-oxy-neolignan 4-O-β-d-glucopyranoside (5), along with three known compounds (6-8). Their structures were established mainly on the basis of 1D and 2D NMR spectral data, ESI–MS and comparison with the literature. Compounds 1-8 were tested in vitro for their cytotoxic activity against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Compounds 3 and 5 exhibited cytotoxic activity against Lovo cells, with IC₅₀ value of 10.4 μM and 8.5 μM, respectively.     

Ligand chirality-controlled selective formation of mono- and dinuclear copper complexes

Reaction of copper(II) acetate with the (S)-enantiomer of a tridentate binaphthyl Schiff base ligand, 2-(3,5-dichloro-2-hydroxybenzylideneamino)-2′-hydroxy-1,1′-binaphthyl (H₂L), in methanol afforded mononuclear copper(II) complex [Cu^II(HL)₂] ((S,S)-1) in 52% isolated yield. The same reaction gave dinuclear copper(II) complex [Cu^II₂(L)₂] ((R,S)-2) in 73% isolated yield when racemic-H₂L was used instead of (S)-H₂L. Both complexes (S,S)-1 and (R,S)-2 were characterized by elemental analysis, mass spectrometry, and X-ray crystallography. The present work highlights the functioning of ligand chirality as a ‘switch’ for selective formation of mono- and dinuclear metal complexes.     

Discovery of (1R,6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a): Histamine H3 receptor inverse agonist demonstrating potent cognitive enhancing and wake promoting activity

A series of fused cyclopropyl-4,5-dihydropyridazin-3-one (3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one) phenoxypiperidine analogs was designed and synthesized, leading to the identification of (1R,6S)-5-[4-(1-cyclobutyl-piperidin-4-yloxy)-phenyl]-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one (R,S-4a) as a second-generation pyridazin-3-one H₃R antagonist. Compound R,S-4a was a potent H₃R functional antagonist in vivo in the rat dipsogenia model, demonstrated potent wake activity in the rat EEG/EMG model, and enhanced short-term memory in the rat social recognition memory model at doses as low as 0.03–0.3 mg/kg po.     

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC₅₀ value of 15.41?μM.     

Diamidato-bis(diphenylphosphino) platinum(II) complexes: Synthesis, characterization, and reactivity in the presence of acid

The reaction of Pt(COD)Cl₂, where COD is 1,5-cyclooctadiene, with one equivalent of a diamidato-bis(phosphino) Trost ligand ((R,R)-2 = N,N′-bis(2-diphenylphosphino-1-benzoyl)-(1R,2R)-1,2-diaminocyclohexane, (R,R)-3 = N,N′-bis(2-diphenylphosphino-1-naphthoyl)-(1R,2R)-1,2-diaminocyclohexane, or (±)-4 = N,N′-bis(2-diphenylphosphino-1-benzoyl)-1,2-bis(aminobenzene)) in the presence of base afforded square planar diamidato-bis(phosphino) platinum(II) complexes (R,R)-2-Pt, (R,R)-3-Pt, (±)-4-Pt. Characterization of all complexes included the solution and solid state structure determination of each complex based on multinuclear NMR and X-ray analyses, respectively. Stability of the complexes in acid was examined on addition of HCl to (R,R)-2-Pt in chloroform and compared to the unreactive nature of the similar diamidato-bis(phosphino) complex 1-Pt (1 = 1,2-bis-N-[2′-(diphenylphosphino)benzoyl]diamino-benzene) in the presence of acid. Protonation of the bound amidato nitrogen atoms of (R,R)-2-Pt was observed along with decoordination of the nitrogen atoms from the platinum(II) center producing (R,R)-2-PtCl₂ in quantitative yield by NMR analysis. Confirmation of the product was made on comparison of the NMR spectra to that of authentic (R,R)-2-PtCl₂ prepared on reaction of Pt(COD)Cl₂ with (R,R)-2 in CH₂Cl₂ and characterized by single-crystal X-ray diffraction analysis and NMR spectroscopy. Results add to the knowledge of rich coordination chemistry of bis(phosphino) ligands with late transition metals, metal-amidato chemistry, and has implications in catalysis.     

Dimeric argininamide-type neuropeptide Y receptor antagonists: Chiral discrimination between Y1 and Y4 receptors

The structurally related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are endogenous agonists of the NPY receptor (YR) family, which in humans comprises four functionally expressed subtypes, designated Y₁R, Y₂R, Y₄R and Y₅R. Nonpeptide antagonists with high affinity and selectivity have been described for the Y₁R, Y₂R and Y₅R, but such compounds are still lacking for the Y₄R. In this work, the structures of the high affinity selective (R)-argininamide-type Y₁R antagonists BIBP3226 and BIBO3304 were linked via the guanidine or urea moieties to give homo-dimeric argininamides with linker lengths ranging from 31 to 41 atoms. Interestingly, the twin compounds proved to be by far less selective for the Y₁R than the R-configured monovalent parent compounds. The decrease in selectivity ratio was most pronounced for Y₁R versus Y₄R subtype, resulting in comparable affinities of bivalent ligands for Y₁R and Y₄R (e.g. UR-MK177 ((R,R)-49): K_i = 230 nM (Y₁R) and 290 nM (Y₄R)). With a K_i value of 130 nM and a K_b value of 20 nM, UR-MK188 ((R,R)-51) was superior to all Y₄R antagonists known to date. The S,S-configured optical antipodes of UR-MK177 and UR-MK188 (UR-MEK381 ((S,S)-49) and UR-MEK388 ((S,S)-51)) were synthesized to investigate the stereochemical discrimination by the different receptor subtypes. Whereas preference for R,R-configured argininamides was characteristic of the Y₁R, stereochemical discrimination by the Y₄R was not observed. This may pave the way to selective Y₄R antagonists.     

An efficient lipase-catalyzed enantioselective hydrolysis of (R,S)-azolides derived from N-protected proline, pipecolic acid, and nipecotic acid

In the Candida antarctica lipase B-catalyzed hydrolysis of (R,S)-azolides derived from (R,S)-N-protected proline in water-saturated methyl tert-butyl ether (MTBE), high enzyme activity with excellent enantioselectivity (V _S V _R ^?1 ?>?100) for (R,S)-N-Cbz-proline 1,2,4-triazolide (1) and (R,S)-N-Cbz-proline 4-bromopyrazolide (2) was exploited in comparison with their corresponding methyl ester analog (3). Changing of the substrate structure, water content, solvent, and temperature was found to have profound influences on the lipase performance. On the basis of enzyme activity and enantioselectivity and solvent boiling point, the best reaction condition of using 1 as the substrate in water-saturated MTBE at 45 °C was selected and further employed for the successful resolution of (R,S)-N-Cbz-pipecolic 1,2,4-triazolide (5) and (R,S)-N-Boc-nipecotic 1,2,4-triazolide (9). Moreover, more than 89.1 % recovery of remained (R)-1 is obtainable in five cycles of enzyme reusage, when pH 7 phosphate buffers were employed as the extract at 4 °C.     

Design,synthesis and evaluation of [3H]PF-7191, a highly specific nociceptin opioid peptide (NOP) receptor radiotracer for in vivo receptor occupancy (RO) studies

Herein we report the identification of (+)-N-(2-((1H-pyrazol-1-yl)methyl)-3-((1R,3r,5S)-6′-fluoro-8-azaspiro[bicyclo[3.2.1]octane-3,1′-isochroman]-8-yl)propyl)-N-[³H]-methylacetamide {[³H]PF-7191 [(+)-11]} as a promising radiotracer for the nociceptin opioid peptide (NOP) receptor. (+)-11 demonstrated high NOP binding affinity (K_i = 0.1 nM), excellent selectivity over other opioid receptors (>1000×) and good brain permeability in rats (C_b,u/C_p,u = 0.29). Subsequent characterization of [³H](+)-11 showed a high level of specific binding and a brain bio-distribution pattern consistent with known NOP receptor expression. Furthermore, the in vivo brain binding of [³H](+)-11 in rats was inhibited by a selective NOP receptor antagonist in a dose–responsive manner. This overall favorable profile indicated that [³H](+)-11 is a robust radiotracer for pre-clinical in vivo receptor occupancy (RO) measurements and a possible substrate for carbon-11 labeling for positron emission tomography (PET) imaging in higher species.     

Anti-hepatitis B virus lignans from the root of Streblus asper

Four new lignans, strebluslignanol F (1), (7′R,8′S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5–16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through various spectroscopic methods, including 1D NMR (¹H NMR, ¹³C NMR), 2D NMR (HMQC, HMBC and NOESY) and HRMS. The stereochemistry at the chiral centers was determined using CD spectra, as well as analyses of coupling constants and optical rotation data. The isolated lignans were evaluated for their anti-HBV activities in vitro using the HBV transfected HepG2.2.15 cell line. The most active lignans, (7′R,8′S,7″R,8″S)-erythro-strebluslignanol G, magnolol, isomagnolol and isolariciresinol, exhibited significant anti-HBV activities with IC₅₀ values of 1.58, 2.03, 10.34 and 3.67 μM, respectively, for HBsAg with no cytotoxicity, and of 3.24, 3.76, 8.83 and 14.67 μM, respectively, for HBeAg with no cytotoxicity. (7′R,8′S,7″R,8″S)-erythro-Strebluslignanol G and magnolol showed significant anti-HBV activities to inhibit the replication of HBV DNA with the IC₅₀ values of 9.02 and 8.67 μM, respectively.     

Improvement of carbonyl reductase activity for the bioproduction of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate

tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key chiral intermediate for the side chain synthesis of rosuvastatin. In this study, random mutagenesis, site-saturation mutagenesis and combinatorial mutagenesis methods were applied to improve the activity of a synthesized stereoselective short chain carbonyl reductase (SCR) to prepare (3R,5S)-CDHH. After screened by high-throughput screening method and high-performance liquid chromatography, mut-Phe145Met/Thr152Ser and mut-Phe145Tyr/Thr152Ser, were obtained, and the enzyme activities of mutants were improved by 1.60- and 1.91-fold compared with parent enzyme, respectively. The catalytically efficiencies (kcat/Km) of mut-Phe145Met/Thr152Ser and mut-Phe145Tyr/Thr152Ser exhibited 5.11- and 8.07-fold improvements in initial activity toward (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH), respectively. In the asymmetric reduction, mut-Phe145Tyr/Thr152Ser catalyzed 500 g L⁻¹ of (S)-CHOH to produce (3R,5S)-CDHH with >99% yield and >99% e.e., and the highest space-time yield achieved at 752.76 mmol L⁻¹ h⁻¹ g⁻¹ wet cell weight within 8 h bioconversion. This study provides a foundation for the preparation of (3R,5S)-CDHH by carbonyl reductase.     

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC₅₀ = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC₅₀ = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC₅₀ = 1129.32 ± 88.79 μM) and α-tocopherol (EC₅₀ = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC₅₀ = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC₅₀ = 157.54 ± 21.30 μM; synthetic (R,R)-SDG-2: EC₅₀ = 123.63 ± 8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use.     

Synthesis of 6-substituted uridines. synthesis of (R or S)-6-(3-amino-2-carboxypropyl)uridine

Addition of 5-bromo-2′,3′-O-isopropylidene-5′-O-trityluridine (2) in pyridine to an excess of 2-lithio-1,3-dithiane (3) in oxolane at 78° gave (6R)-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene -5′-O-trityluridine (4), (5S,6S)-5-bromo-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene-5′-O-trityluridine (5), and its (5R) isomer 6 in yields of 37, 35, and 10%, respectively. The structure of 4 was proved by Raney nickel desulphurization to (6S)-5,6-dihydro-2′,3′-O-isopropylidene-6-methyl-5′-O-trityluridine (7) and by acid hydrolysis to give D-ribose and (6R)-5,6-dihydro-6-(1,3-dithian-2-yl)uracil (9). Treatment of 4 with methyl iodide in aqueous acetone gave a 30&%; yield of (R,S)-5,6-dihydro-6-formyl-2′,3′-O-isopropylidene-5′-O-trityl-uridine (10), characterized as its semicarbazone 11. Both 5 and 6 gave 4 upon brief treatment with Raney nickel. Both 5 and 6 also gave 6-formyl-2′,3′-O-isopropylidene-5′- O-trityluridine (12) in ～41%; yield when treated with methyl iodide in aqueous acetone containin- 10%; dimethyl sulfoxide. A by-product, identified as the N-methyl derivative (13) of 12 was also formed in yields which varied with the amount of dimethyl sulfoxide used. Reduction of 12 with sodium borohydride, followed by deprotection, afforded 6-(hydroxymethyl)uridine (17), characterized by hydrolysis to the known 6-(hydroxymethyl)uracil (18). Knoevenagel condensation of a mixture of the aldehydes 12 and 13 with ethyl cyanoacetate yielded 38%; of E- (or Z-)6-[(2-cyano-2-ethoxycarbonyl)ethylidene]-2′,3′-O-isopropylidene-5′-O-trityluridine (19) and 10%; of its N-methyl derivative 20. Hydrogenation of 19 over platinum oxide in acetic anhydride followed by deprotection gave R (or S)-6-(3-amino-2-carboxypropyl)uridine (23).     

Trichodiene biosynthesis and the stereochemistry of the enzymatic cyclization of farnesyl pyrophosphate

Cyclization of trans,trans-[1-³H₂,12,13-¹⁴C]farnesyl pyrophosphate (2a) by a preparation of trichodiene synthetase isolated from the fungus, Trichothecium roseum, gave trichodiene (5a), which was shown by chemical degradation to retain both tritium atoms of the precursor at C-11. Incubation of 1S-[1-³H,12,13-¹⁴C]farnesyl pyrophosphate (2b) and 1R-[1-³H,12,13-¹⁴C]farnesyl pyrophosphate (2c) with trichodiene synthetase and degradation of the resulting labeled trichodienes, 5b and 5c, established that the displacement of the pyrophosphate moiety from C-1 of the precursor and formation of the new C-C bond in the formation of trichodiene takes place with net retention of configuration. These results are accounted for by an isomerization-cyclization mechanism involving the intermediacy of nerolidyl pyrophosphate (4).     

Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands

Four novel iridium(III) complexes with enantiopure C₂-symmetrical vicinal diamine ligands were designed, synthesized, and characterized by FT-IR, NMR, and MS. The cytotoxicities of all of the complexes against the human solid tumor cell lines A2780, A549, KB, and MDA-MB-231 were evaluated. Both R,R-configured complexes (R,R)-5a and (R,R)-5b exhibited more potent or similar activity compared with oxaliplatin, whereas their corresponding (S,S)-isomers (S,S)-5a and (S,S)-5b were found to be mostly inactive. As indicated by the activation of caspase-3, the cleavage of PARP, and the upregulation of p53, the preliminary mechanism studies revealed that the mode of cell death initiated by (R,R)-5a in A2780 cells was predominantly p53-mediated apoptosis. In addition, the structure of (R,R)-5a was unambiguously confirmed through single crystal X-ray structure determination.     

Evaluation of enantioselectivity in lipase-catalyzed acylation of hydroxyalkylphosphine oxides

The lipase-catalyzed optical resolution of 2-, 3-, and 5-hydroxyalkyl phosphorus compounds 1 provided the corresponding optically pure diastereomers in good yields. (S_P, R)- and (R_P, S)-1 were acylated faster than (S_P, S)- and (R_P, R)-1. The stereoselectivity at the phosphorus atom changed with the flexibility of the active sites in the lipases. The stereoselectivity at the phosphorus atom was higher in the reaction of 1a than in the reaction of 1b,c. The reaction rate of ɛ-hydroxyalkylphosphine oxide 1c was faster than that of 1a, although less enantioselectivity was observed at the phosphorus atom.     

Facile route for the synthesis of the iminosugar nucleoside (3R,4R)-1-(pyren-1-yl)-4-(hydroxymethyl)pyrrolidin-3-ol

N-(Pyren-1-yl)-(3R,4S)-4-[(1S,2R)-1,2,3-trihydroxypropyl]pyrrolidin-3-ol (4) was obtained in 36% yield from 3-deoxy-3-C-formyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (3) by combined hydrolysis and aminoalkylation reactions with 1-aminopyrene in a one-pot reaction. Cleavage reactions of the exocyclic triol chain in 4 with NaIO₄ and NaBH₄ resulted in iminosugars 7 and 8, which are analogues of the furanose forms of 2-deoxy-d-allose and of 2-deoxy-d-ribose, the latter analogue N-(pyren-1-yl)-(3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol (8) being formed in 83% yield.     

Structural-guided design to improve the catalytic performance of aldo-keto reductase KdAKR

Aldo-keto reductases (AKRs) are important biocatalysts that can be used to synthesize chiral pharmaceutical alcohols. In this study, the catalytic activity and stereoselectivity of a NADPH-dependent AKR from Kluyveromyces dobzhanskii (KdAKR) toward t-butyl 6-chloro (5S)-hydroxy-3-oxohexanoate ((5S)-CHOH) were improved by mutating its residues in the loop regions around the substrate-binding pocket. And the thermostability of KdAKR was improved by a consensus sequence method targeted on the flexible regions. The best mutant M6 (Y28A/L58I/I63L/G223P/Y296W/W297H) exhibited a 67-fold higher catalytic efficiency compared to the wild-type (WT) KdAKR, and improved R-selectivity toward (5S)-CHOH (de_p value from 47.6% to >99.5%). Moreover, M6 exhibited a 6.3-fold increase in half-life (t_1/2) at 40°C compared to WT. Under the optimal conditions, M6 completely converted 200 g/L (5S)-CHOH to diastereomeric pure t-butyl 6-chloro-(3R, 5S)-dihydroxyhexanoate ((3R, 5S)-CDHH) within 8.0 h, with a space-time yield of 300.7 g/L/day. Our results deepen the understandings of the structure−function relationship of AKRs, providing a certain guidance for the modification of other AKRs.     

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.     

Two new pterosin sesquiterpenes from Pteris multifida Poir

Two new pterosin sesquiterpenes named as 2R,3R-13-hydroxy-pterosin L 3-O-β-d-glucopyranoside (1) and 2R,3S-acetylpterosin C (2), along with a known one, 2S,3S-acetylpterosin C (3), were isolated from the whole plant of Pteris multifida and the 1D and 2D NMR data of 3 were reported for the first time in this paper. Their structures were elucidated on the basis of mass and spectral evidence. Compounds 1–3 showed cytotoxicity against HL 60 cells (human leukemia) with the IC₅₀ values of 14.6, 48.3 and 35.7 μM, respectively.