Isolation and characterization of three pairs of indolediketopiperazine enantiomers containing infrequent N-methoxy substitution from the marine algal-derived endophytic fungus Acrostalagmus luteoalbus TK-43

Three pairs of new N-methoxy-containing indolediketopiperazine enantiomers, acrozines A–C (1–3), were isolated from the culture extract of Acrostalagmus luteoalbus TK-43, an endophytic fungus obtained from the marine green alga Codium fragile. The optical resolution of compounds 1–3 by chiral HPLC successfully afforded individual enantiomers (+)-1/(–)-1, (+)-2/(–)-2, and (+)-3/(–)-3, respectively. The structures of all these compounds were established on the basis of detailed interpretation of their NMR and mass spectroscopic data. X-ray crystallographic analysis confirmed the structures of compounds 1–3, while the absolute configurations were determined by TDDFT-ECD calculations. All these compounds containing a N-methoxy group which is uncommon in indolediketopiperazines. The enantiomers, (+)-2/(–)-2, showed different antimicrobial activities against several plant-pathogenic fungi, while (+)-1 displayed better inhibitory activity against acetylcholinesterase than that of (–)-1.     

New hexalactone derivatives and a pair of new oxaspiro-carbon epimeric glycosides from the fruits of Illicium lanceolatum

Five new compounds (1–5), including three hexalactone derivatives (1–3) and a pair of new oxaspiro-carbon epimeric glycosides (4 and 5), and six known compounds (6–11) were obtained from the fruits of Illicium lanceolatum. The structures of the new compounds were elucidated using extensive spectroscopic data. The absolute configurations of compounds 1–3 were determined by an analysis of their CD spectra. It was determined that compounds 4 and 5, which are epimeric at C-5, possess the same 1-oxaspiro[4,5]decane-7α,8α,9β-triol moiety. Plausible biogenetic pathways for 4 and 5 derived from the key precursor shikimic acid were proposed. Compounds 1–11 were all assayed on monosodium glutamate-induced human neuroblastoma SH-SY5Y cell damage. The results demonstrated that compounds 4, 5, and 8–10 possess potential neuroprotective effects. The anti-inflammatory, antiviral, and cytotoxic activities of 1–11 were also evaluated.     

Chemical constituents from the roots of Asarum sieboldii Miq. var. Seoulense Nakai

Fourteen compounds were isolated from the 95% ethanol reflux extract of Asarum sieboldii Miq. var. Seoulense Nakai, including five phenanthrene derivatives (1–5), three isobutyl amides (6–8), three phenylpropanoids (9–11) and three lignins (12–14). The structures of these compounds were identified by spectroscopic methods and by comparison with the reported spectroscopic data. Among them, compounds 6 and 11 were firstly reported from the family Aristolochiaceae, and compounds 3 and 4 were reported for the first time from the genus Asarum. Additionally, compounds 1, 2 and 8 were isolated from A. sieboldii Miq. var. Seoulense Nakai for the first time. These compounds have shown chemical relationships between A. sieboldii Miq. var. Seoulense Nakai and other species of Asarum as well as those found in the genus Aristolochia in the family Aristolochiaceae.     

Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from Cratoxylum cochinchinense

Four new caged xanthones (1–4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1–6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1–6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC₅₀ values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining K_m, V_max, and the ratio of K_ik and K_iv, which revealed that all the compounds behaved as competitive inhibitors.     

A new bicyclic sesquiterpenoid from Merremia yunnanensis

A new sesquiterpenoid, 1α,4β,8β,9β-eudesmane-tetrol-1-O-β-D-glucopyranoside (1), together with nine known compounds (2–10), were isolated from Merremia yunnanensis. The structures of these compounds were elucidated by spectroscopic methods and compared to data in the literature. All these compounds (1–10) were firstly isolated from this plant, and compounds 3, 5, 7, and 10 were reported from the Merremia genus for the first time. The significance of the chemotaxonomy for these compounds is described herein.     

A novel eudesmane sesquiterpene glycoside from Ambrosia artemisiifolia L.

A new eudesmane sesquiterpene glycoside (1), five known eudesmane sesquiterpenoids (2–6), and seven known compounds (7–13), were obtained from Ambrosia artemisiifolia. Their structures were elucidated mainly by NMR and MS methods. Among them, compounds 1–4 and 6–9 were isolated from the A. artemisiifolia for the first time and the chemotaxonomic significance of these compounds was summarized.     

Bioactive new withanolides from the cultured soft coral Sinularia brassica

Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H–L (1–5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1–5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1–6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.     

New cis-ent-clerodanes from Linaria japonica

Five new cis-ent-clerodanes, linarenones A–E (1–5) and two known compounds (6 and 7) were isolated from whole plant of Linaria japonica. The structures of these compounds were determined by various spectroscopic analyses (UV, IR, HR–ESI–MS, 1D and 2D NMR). The absolute configuration of five new diterpenoids was confirmed by circular dichroism (CD) analysis and chemical conversion. Cytotoxicity of the isolated compounds against A549 cell lines and Leishmania major were evaluated. The new cis-ent-clerodane 3 was found to be moderately active against A549 cell lines, and new cis-ent-clerodanes 1, 6 and desacetyl-linarienone (7) were active against L. major.     

Antimicrobial effects of N-benzyloxycarbonyl-S-(2,4-dinitrophenyl) glutathione diesters against chloroquinine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum

N-Benzyloxycarbony-S-(2,4-dinitrophenyl)glutathione diesters have been investigated for antimalarial activity against chloroquinine sensitive (NF54) and resistant (K1) strains of P. falciparum. Both strains appear equally susceptible to inhibition by compounds 1–4, with an IC₅₀ ∼ 4.92–6.97 μM, consistent with the target of these compounds being the PfMRP transporter. Against the NF54 strain, diester derivatives containing ethyl side chains showed lower in vitro activity than those with methyl side chains 1–4, IC₅₀ ∼ 5.7–6.97 μM with the exception of compound 5 (IC₅₀ > 25 μM). The cytotoxicity of compounds with log P ∼ 3.9–5.8 were lower against the murine L6 cell line than compounds with a higher log P > 5.8 that were toxic. Overall the cytotoxicity of compounds 1–7 were lower against KB cells than against the L6 cell line with the exception of compound 4, which showed a higher relative toxicity.     

Evolvosides C–E,flavonol-4-O-triglycosides from Evolvulus alsinoides and their anti-stress activity

Phytochemical investigation of the n-butanol fraction of Evolvulus alsinoides (Linn.) led to the isolation of three new phenolic glycosides, evolvosides C, D and E (1–3) along with six known compounds (4–9). The structures of the compounds were elucidated on the basis of spectroscopic analysis, viz. 1D and 2D NMR experiments, chemical study, and comparison with literature data. Evolvoside C (1) was characterized as kaempferol 4′-O-β-d-glucopyranosyl-(1→2)-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside, whereas evolvosides D and E (2–3) were found to be mono and di-O-methyl derivatives of 1. The new compounds (1–3) represent rare triglycoside derivatives of flavonol at C-4′. The isolated compounds (1–6) were screened for acute stress-induced biochemical changes in male Sprague–Dawley rats at a dose of 40 mg/kg body weight. Compounds 1 and 2 displayed anti-stress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 3 and 6 were also found to be effective in normalizing most of these stress parameters, whereas compounds 4 and 5 were ineffective in normalizing most of these effects.     

Chemical constituents from Cistanche sinensis (Orobanchaceae)

Phytochemical investigation of 70% aqueous EtOH extract of Cistanche sinensis led to the isolation of fifteen compounds (1–15), including nine phenylethanoid glycosides (PhGs, 1–9), five iridoid glycosides (10–14), and one lignan glycoside (15). Their structures were determined on the basis of 1D- and 2D-NMR experiments and by comparison with physical data of known compounds. Among the isolated compounds, 1 was identified as a new compound, three compounds (9, 14, and 15) were firstly reported from the genus Cistanche, and seven compounds (2–6, 11, and 12) were isolated from C. sinensis for the first time. PhGs with a 6′-O-rhamnosyl moiety such as cistansinenside B (1), poliumoside (7), and 2′-O-acetylpoliumoside (9) could serve as chemotaxonomic markers to differentiate C. sinensis from other species of Cistanche.     

Cytotoxic ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata

Euphoroids A–C (1–3), three new ent-abietane-type diterpenoids, together with ten known analogues (4–13) were obtained from the roots of Euphorbia ebracteolata. The structures of these compounds were determined by extensive spectroscopic data analysis, including UV, HRESIMS, 1D-, and 2D-NMR data. The inhibitory effects of compounds 1–13 on human cancer cells were determined using the MTT assay. The results revealed that new compounds 2 and 3 showed moderate cytotoxic activities against human cancer cell lines. Especially, compound 3 displayed selective cytotoxic effect agains cancer cell lines.     

Synthesis of 4-substituted pyrido[2,3-d]pyrimidin-4(1H)-one as analgesic and anti-inflammatory agents

4-Substituted-pyrido[2,3-d]pyrimidin-4(1H)-ones 4a–c were synthesized by oxidation of 4-substituted-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones 3a–c which were in turn prepared from arylidenemalononitriles 1a–c and 6-aminothiouracil 2. The reactivity of compounds 4a–c towards some reagents such as formamide, carbon disulfide, urea, thiourea, formic and acetic acids were studied. All the synthesized compounds were characterized by spectroscopic means and elemental analysis. Compound 4c exhibited 64% and 72% analgesic activity. Also, compound 4b showed 50% and 65% anti-inflammatory activity. Interestingly these compounds showed one-third of ulcer index of the reference aspirin and diclofenac.     

Chemical constituents from Euphorbia stracheyi Boiss

The chemical investigation of whole plants Euphorbia stracheyi Boiss. led to the isolation of 14 compounds, including eight diterpenes (1–8), one monoterpene (9), three coumarins (10–12), and two phenols (13–14). Their structures were elucidated by extensive spectroscopic analyses and by comparison with the literature. Compounds 1–6, and 8–12 were firstly isolated from E. stracheyi, while compounds 6, and 9 were isolated from Euphorbia genus for the first time. The chemotaxonomic significance of these isolated compounds is discussed.     

Chemical constituents from the calyces of Physalis alkekengi var. franchetii

One new monoterpenoid glycoside (1), together with seven known compounds, including two alkaloids (2–3), three phenylpropanoids (4–6), and two nucleosides (7–8) were isolated from the calyces of Physalis alkekengi var. franchetii. Their structures were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. These eight compounds were isolated for the first time from the genus Physalis. The chemotaxonomic significance of these compounds was summarized.     

Chemical constituents from Piper boehmeriifolium (Miq.) Wall. ex C. DC

The chemical investigation of whole plants Piper boehmeriifolium (Miq.) Wall. ex C. DC. led to the isolation of 22 compounds, including two lignans (1–2), sixteen amide alkaloids (3–18), one diterpene (19), two monoterpenes (20–21), and one phenylpropanoid (22). Their structures were elucidated by extensive spectroscopic analyses including NMR, MS, and by comparison with the literature. Compounds 1–2, 6–7, 11–12, 14, and 17–22 were firstly isolated from P. boehmeriifolium, while compounds 2, and 19–20 were isolated from Piper genus for the first time. The chemotaxonomic significance of these isolated compounds is discussed.     

Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis,characterization and antimicrobial evaluation

A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a–m) were synthesized either by cyclization of N′-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl₃ at 120 °C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N′-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a–d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR and LC–MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20–50 μg mL⁻¹ against bacteria and 25–55 μg mL⁻¹ against fungi. The title compounds represent a novel class of potent antimicrobial agents.     

Chemical constituents from the flower buds of Daphne genkwa (Thymelaeaceae)

Phytochemical investigation on the flower buds of Daphne genkwa led to the isolation of 22 compounds, including 17 daphne diterpenes (1–17), three tigliane types (18–20), and two diphenylpentanes (21–22). Compounds 19–21 were isolated from D. genkwa for the first time. These compounds were elucidated using spectroscopic methods and by comparing their data to those reported in the literature. On the basis of chemical research, the chemotaxonomic significance of the isolated compounds were discussed.     

Flavonoids,stilbenoids, and phenolic derivatives from the stems of Gnetum macrostachyum (Gnetaceae)

Gnetum species have been traditionally consumed as food and used as folk medicine to treat various pathological conditions. Ten compounds including three simple phenolic compounds (1–3), five stilbenoids (4, 5, 8–10), and two C-glycosyl flavanones (6 and 7), were isolated from the stems of Gnetum macrostachyum Hook. f. The structures of these compounds were elucidated by the analysis of spectroscopy data and their comparison with the reported values. This is the first report of the isolation of compounds 1–4 and 6–9 from G. macrostachyum. Compounds 1–3, 6, and 7 have not been previously reported from the genus Gnetum. The C-glycosyl flavanones in G. macrostachyum can be used as chemotaxonomic markers.     

Chemical constituents from the fruits of Zanthoxylum bungeanum and their chemotaxonomic significance

The phytochemical study of the fruits of Zanthoxylum bungeanum Maxim led to the isolation of sixteen compounds, including a new compound zantharin (1) and fifteen other known compounds, which consist of ten coumarins (2–11), three alkaloids (12–14), and two phenols (15–16). Their structures were elucidated based on extensive spectroscopic methods (1D and 2D NMR, HRESIMS, UV, and IR experiments) and by comparison with literature data. In this work, all the compounds were isolated from Z. bungeanum for the first time, in which, compounds 5 and 13–16 were reported for the first time from the genus Zanthoxylum and the Rutaceae family, respectively. Moreover, the chemotaxonomic significance of isolated compounds is discussed.