Cytotoxic withanolides from the aerial parts of Tubocapsicum anomalum

Ten new withanolides (1–10) and three artificial withanolides (11–13) were isolated from the aerial parts of Tubocapsicum anomalum, together with five known analogues (14–18). Their structures were determined on the basis of extensive spectroscopic and chemical methods. They include seven acnistin–type (1–4, 11, 14 and 15), three withajardin–type (5–7), and eight normal–type (8–10, 12, 13 and 16–18) withanolides. Of normal–type withanolides, a chemical conversion from the 16α,17α–epoxywithanolide (16) to Δ^13,14–16α–hydroxywithanolide (18) was achieved by Wagner–Meerwein rearrangement. All isolates were evaluated for their cytotoxicity against four human tumor cell lines (HCT–116, HepG2, MCF–7 and A375). Among them, compounds 1–3, 6–8, 14, 16–18 showed cytotoxic activity with IC₅₀ values of 0.24–8.71 μM.     

Antiproliferative terpenoids and alkaloids from the roots of Maytenus vitis-idaea and Maytenus spinosa

Investigation of the organic extracts of the roots of Maytenus vitis-idaea and Maytenus spinosa, collected in the province of Salta, Argentina, led to isolation of eighteen compounds belonging to several classes. From M. vitis-idaea, eight methylenequinone celastroids (1–8) were isolated, four of which (4–7) were hitherto unknown. Additionally, from M. spinosa, two known celastroids, a known celastroid dimer (9), three pentacyclic triterpenoids (10–12) and six β-dihydroagarofuran sesquiterpenoid alkaloids (13–18) were identified. Compounds 4–7 were active against six solid tumor cell lines at micromolar concentrations.     

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.     

Flavonoid glycosides from the aerial parts of Curcuma comosa

Four new flavonoid glycosides, curcucomosides A–D (1–4), three known flavonoid glycosides, 5–7, and four known diarylheptanoids, 8–11, were isolated from the ethanol extract of the aerial parts of Curcuma comosa. The structures of the new compounds were established as rhamnazin 3-O-α-l-arabinopyranoside (1), rhamnocitrin 3-O-α-l-arabinopyranoside (2), rhamnazin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (3), and rhamnocitrin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (4) by spectroscopic analysis and chemical reactions whereas those of the known compounds were identified by spectral comparison with those of the reported values.     

Phytochemical investigation on the roots of Juglans mandshurica and their chemotaxonomic significance

Phytochemical research of the roots of Juglans mandshurica Maxim. (Juglandaceae) verified 37 secondary metabolites, including thirteen diarylheptanoids (1–13), five naphthoquinones (14–18), five tetralones (19–23), three lignans (24–26), three phenols (27–29), two anthraquinones (30–31), two triterpenoids (32–33), two secoiridoids (34–35), one naphthalenyl glycoside (36), and one flavonoid (37). The chemical structures of these constituents were elucidated by NMR spectroscopy and compared with data from the literature. This is the first confirmation of the presence of ten compounds (6, 12, 16, 18, 24–26, 30, 32–33) isolated from the family Juglandaceae, two compounds (1 and 8) from the genus Juglans, and four compounds (27, 31, 34–35) from J. mandshurica. The isolation and chemotaxonomic significance of the metabolites from the roots of J. mandshurica were described in this study.     

Chemical constituents from the roots of Zizyphus jujuba Mill. var. spinosa

One new flavonoid, named (R)-2-hydroxynaringenin (1), along with fifteen known compounds, including six flavonoids (2–7), six lignans (8–13), two phenolic glycosides (14–15) and one alkaloid (16) were isolated from the roots of Zizyphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. Their structures were established on the basis of spectroscopic evidence, including 1D and 2D NMR, circular dichroism (CD) curve analysis, and by comparison with literature data. Compounds 2, 3 and 8–16 were found in Z. jujuba Mill. var. spinosa for the first time, while compounds 8, 10 and 13–15 were new to the Rhamnaceae family. In addition, the chemotaxonomic significance of the isolates was discussed in this paper.     

Meroterpenoids from the fruiting bodies of higher fungus Ganoderma resinaceum

Phytochemical investigation on the fruiting bodies of Ganoderma resinaceum led to the isolation of five new meroterpenoids, namely ganoresinains A–E (1–5), and four known analogues (6–9). The new compounds were identified by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparison with the literature data. Compound 1 and 6 were isolated as enantiomeric mixture, which were separated over analytical chiral HPLC chromatography. Compounds 6–9 were isolated from G. resinaceum for the first time.     

Chemical constituents of the roots of Scorzonera divaricata and their chemotaxonomic significance

The phytochemical study of the roots of Scorzonera divaricata Turcz led to the isolation of 27 compounds, including eight sterols (1–8), one lignan (9), two cumarins (10, 11), five phenylpropanoids (12–16), six benzene derivatives (17–22), methyl-β-D-fructofuranoside (23), monolinolein (24), and three aliphatic acids (25–27). The structures of isolated compounds were identified using NMR and ESI-MS spectroscopic methods and comparing them with those previously reported. Except for β-daucosterol (8), scopoletin (10) and caffeic acid (16) from S. divaricata, this is the first report of the other 24 compounds from S. divaricata. Among them, eleven compounds (2–6, 11, 17, 19, 20, 23, 25) were reported from genus Scorzonera for first time, suggesting that they could be used to distinguish S. divaricata from the other species of Scorzonera. Furthermore, the chemotaxonomic significance of isolated compounds from S. divaricata has also been discussed.     

Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions

Trimellitimides 6–21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6–11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED₅₀) of 34.3–49.8 mg kg⁻¹ and 63.6–86.6% edema inhibition relative to the reference drug celecoxib (ED₅₀: 33.9 mg kg⁻¹ and 85.2% edema inhibition). Compounds 6–11 and 18 were weakly cytotoxic at 10 μM against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6–11 had optimal selectivity against COX-2. The selectivity index (SI) range was >200–490 and was comparable to that for celecoxib [COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16–18 were nonselective COX inhibitors with a selectivity index range of 0.92–0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6–11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The K_I ranges were 54.1–81.9 nM for hCA I, 25.9–55.1 nM for hCA II, and 46.0–348.3 nM for hCA IX. © 2018 Elsevier Science. All rights reserved.     

Flavonoids and polyacetylenes from the aerial parts of Bidens tripartita

Fourteen flavonoids (1–14) and two polyacetylenes (15 and 16) were isolated from the aerial parts of Bidens tripartita. Thirteen compounds (1–7, 9, 11, 12, and 14–16) were isolated from this species for the first time, of which a flavonoid (11) was obtained for the first time from the genus Bidens. The chemotaxonomic significance of these compounds was summarized.     

Bioactive seco-abietane rearranged diterpenoids from the aerial parts of Salvia prionitis

Five previously undescribed 4,5-seco-abietane rearrange diterpenoids (1–5, Prionidipene A-E) were isolated from the aerial parts of Salvia prionitis, along with thirteen known seco-abietane diterpenoids (6–18). The structures of 1–5 were elucidated mainly based on analysis of NMR and MS data. The absolute configurations of 1–3 were determined by evaluation of experimental and calculated electronic circular dichroism (ECD) spectra. Putative biosynthetic pathways toward the formation of 1 and 2 are proposed. The nitric oxide (NO) production inhibitory effects of all isolates in lipopolysaccharide (LPS)-induced in RAW 264.7 cells were evaluated. Interestingly, compounds 4 and 9 with a furan-ring showed potent inhibitory activity with IC₅₀ values of 14.56 and 15.11 μM, respectively.     

Three new iridoid glycosides isolated from the traditional herb Siphonostegia chinensis with NF-κB inhibitory activity

Siphonoids A–C (1–3), among which siphonoids A-B (1–2) are rare (E)-p-coumaroyl iridoids, were isolated from Siphonostegia chinensis along with ten known iridoids (4–13) and four lignans (14–17). The structures of the compounds were established by 1D- and 2D-NMR spectroscopy and mass spectrometry. Most of the iridoids isolated from S. chinensis were found to possess (E)-p-coumaroyl iridoid subtype skeletons. Hence, this type of iridoid could be regarded as a chemotaxonomic marker of S. chinensis. The inhibition activities for the NF-κB pathway of iridoids (1–6) were detected. The present results showed that compounds 1–2 and 4–6 processed moderate activity towards the inhibition of NF-κB.     

Chemical constituents of the Piper crocatum leaves and their chemotaxonomic significance

Chemical study of Piper crocatum leaves has led to isolation of a new megastigmane glucoside isomer (18), along with 23 known compounds including fifteen phenolic compounds (1–15), two monoterpenes (16 and 17), three sesquiterpenes (19–21), a phenolic amide glycoside (22), a neolignan (23), and a flavonoid C-glycoside (24). Structures of these compounds were identified via spectroscopic methods and compared with those reported in the literature. Seven compounds (7, 11, 13, 14, 17, 20, and 24) from the P. crocatum species and 17 others (1–6, 8–10, 12, 15–16, 18–19, and 21–23) from the Piper genus and Piperaceae family were isolated and reported for the first time. Furthermore, this study discusses chemotaxonomic relations between P. crocatum and other Piper species.     

Chemotaxonomic significance of sesquiterpenes and amide derivatives from Chloranthus angustifolius Oliv.

Phytochemical investigation of the aerial parts of Chloranthus angustifolius Oliv. (Chloranthaceae) resulted in the isolation and characterization of seven sesquiterpenes (1–7) and six amide derivatives (8–13). All structures were established based on analysis of their spectroscopic data. This is the first report of compounds 2 and 8–13 from the family Chloranthaceae, and the first report of compounds 3–5 from C. angustifolius. Moreover, the chemotaxonomic significance of these compounds was summarized.     

A dihydrochalcone and several homoisoflavonoids from Polygonatum odoratum are activators of adenosine monophosphate-activated protein kinase

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a major cellular energy sensor and master regulator of metabolic homeostasis; thus, AMPK plays a central role in studies on diabetes and related metabolic diseases. From the rhizomes of Polygonatum odoratum (Mill.) Druce, six homoisoflavonoids (1–6) and one dihydrochalcone (7) were isolated, and the structures of polygonatones A–D (4–7) were elucidated by various spectroscopic analyses. Compounds 1–7 were evaluated for their effect on AMPK activation. The amount of active phosphorylated AMPK and acetyl-CoA carboxylase in rat liver epithelial IAR-20 cells increased when the cells were incubated with the aforementioned compounds. Specifically, (3R)-5,7-dihydroxyl-6-methyl-8-methoxyl-3-(4′-hydroxylbenzyl)-chroman-4-one (1), (3R)-5,7-dihydroxyl-6,8-dimethyl-3-(4′-hydroxylbenzyl)-chroman-4-one (2), (3R)-5,7-dihydroxyl-6-methyl-3-(4′-hydroxylbenzyl)-chroman-4-one (3), and polygonatone D (7) exhibited significant activation effects.     

Chemical constituents of Peperomia tetraphylla (Forst. F.) Hooker et Arnott

Sixteen compounds were isolated from the whole herbs of Peperomia tetraphylla (Forst. F.) Hooker et Arnott by phytochemical methods, including eight flavonoids (1–3, 6, 7, 14–16), three lignans (8–10), three beta sitosterols (4, 5, 11), and two phenolic acids (12, 13). Their structures were identified by the analysis of NMR and MS, as well as the comparisons to the reported data. Among them, 2″-O-xylosylisoswertisin (14) was firstly isolated from the Piperaceae family, as well as ten compounds (1–4, 7, 10–11, 13, 15–16) were isolated from P. tytraphylla for the first time. Moreover, the chemotaxonomic significance of constituents isolated from P. tytraphylla was also discussed.     

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.     

Constituents from the pseudofruits of Hovenia dulcis and their chemotaxonomic significance

Sixteen compounds, including six flavonoids (1–6), one lignan (7), three megastigmanes (8–10), three triterpenoids (11–13), and three benzoic acid derivatives (14–16) were isolated and structurally elucidated from the pseudo-fruits of Hovenia dulcis. Their structures were analyzed by NMR spectroscopic and data comparison. Among them, compounds 4, 7–11, 13, 15, and 16 were isolated from the Hovenia genus for the first time. The chemotaxonomic significance of the isolates was also described, which revealed a relationship between H. dulcis and H. acerbar as well as other species belonging to the Rhamnaceae family.     

Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-Chromene derivatives and their cytotoxic activity

A series of novel 2-(1,2,3-triazolylmethoxy) 5a–q and isoxazole tagged 6a–g 2H-Chromene derivatives were prepared starting from salicylaldehyde and ethyl-4,4,4-trifluoroacetoacetate via cyclization to form ethyl 2-hydroxy-2-(trifluoromethyl)-2H-Chromene-3-carboxylate 3. Compound 3 on reaction with propargyl bromide resulted compound 4 and was independently reacted with aryl/alkyl azides and aryl aldoximes obtained 2-(1,2,3-triazolylmethoxy) and isoxazole tagged 2H-Chromene derivatives 5a–q, 6a–i, respectively. Compounds 6 were further hydrolysed to acid derivatives 7a–g. All the products 5a–q, 6a–i, 7a–g were screened for cytotoxic activity against four human cancer cell lines and among all the compounds, 5f, 5g, 5l, 5q showed promising activity at <20 μM concentration.     

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.