Search

Clonorosins A (1) and B (2), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids (3-9), were isolated from the soil-derived fungus Clonostachys rosea YRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental. To assist in determining the absolute configuration of the chiral carbon in the side chain of 2,5-diketopiperazine derivatives, flexible analogues 3i-3iv were synthesized and analyzed. 1 was active against Fusarium oxysporum with an MIC value of 50 μg/mL. 7 and 8 showed excellent activity against human HeLa and HepG2 cells with IC50 values of 0.12-0.60 μM.

Twenty-one aspidosperma-aspidosperma alkaloids, including the new tabernaesines A-J (1-9), were obtained from Tabernaemontana pachysiphon. The structures and absolute configurations were elucidated using HRMS and NMR experiments. Compounds 1-9 possessed a rare spiro heterocycle moiety between the monomeric units, while compounds 4 and 5 were characterized by an indole ring fused with an (N,N-diethyl)methyl amino group. Compounds 1, 5-7, 15, and 16 exhibited moderate cytotoxic potency against various human cancer cell lines at IC50 2.5-9.8 μM.

Twenty-six alkaloids, including the new taberines A–I (1–9), were obtained from Tabernaemontana corymbosa. The structures and absolute configurations were elucidated via MS, NMR, and ECD spectrosco...

Porcine epidemic diarrhea virus (PEDV) has become increasingly problematic around the world, not only for its hazards to livestock but also due to the possibility that it is a zoonotic disease. Although vaccine therapy has made some progress toward PEDV control, additional effective therapeutic strategies against PEDV are needed, such as the development of chemotherapeutic agents. The aim of this work was to identify novel anti-PEDV agents by designing and synthesizing a series of phenanthridine derivatives. Among them, three compounds (compounds 1, 2, and 4) were identified as potent anti-PEDV agents exhibiting suppression of host cell heat shock cognate 70 (Hsc70) expression. Mechanism studies revealed that host Hsc70 is involved in the replication of PEDV, and its expression can be suppressed by destabilization of the mRNA, resulting in inhibition of PEDV replication. Activity against PEDV in vivo in PEDV-infected piglets suggested that phenanthridine derivatives are the first host-acting potential anti-PEDV agents.

Twenty-six alkaloids, including the new taberines A-I (

The phytochemical study of Euphorbia resinifera afforded 18 structurally diverse diterpenoids, including 14 new ingol-type diterpenoids, euphorblins A-N (1-14), a new rhamnofolane diterpenoid, euphorblin O (15), and three known analogues (16-18). The structures of these compounds were deduced using 2D NMR spectroscopy and NOE experiments. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. The abilities of the compounds to enhance lysosomal biosynthesis were evaluated through LysoTracker Red staining. Among the 10 active compounds, compounds 2, 4, and 18 showed remarkable immunofluorescence strength, and their LysoTracker staining intensities were 155.9%, 143.5%, and 140.7%, respectively, greater than that of the control. A series of lysosomal genes were also found to be upregulated by these compounds, which further confirms their ability to induce lysosome biosynthesis and suggests that these diterpenoids have potential as lead compounds for the development of drugs for the treatment of lysosome-related diseases.

Nine new humulane-derived sesquiterpenoids, ochracenes A–I (1–9), were isolated from the Antarctic fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures including absolute configurations were elucidated on the basis of spectroscopic analysis, Mosher’s method, and electronic circular dichroism analysis. Compared with previous humulane-type sesquiterpenoids, ochracenes A–I (1–9) featured novel carbon skeletons with corresponding methyl migration, ring cleavage, and carbon loss. Two unprecedented 8,9-secocyclic sesquiterpenoids (2 and 3) exhibited inhibitory effects on lipopolysaccharide-induced NO release in RAW 264.7 mouse macrophage cell lines with IC50 values of 14.6 ± 0.5 and 18.3 ± 1.7 μM, respectively.

A new coumarin, anisucoumaramide (1), and a new δ-truxinate derivative, anisumic acid (2), were isolated from Clausena anisum-olens. Their structures were elucidated from extensive NMR and MS data. The absolute configurations of the coumarins were assigned using the experimental and calculated electronic circular dichroism data. Anisucoumaramide (1) represents the first example of a naturally occurring coumarin of which the terpenoidal side chain does not comply with the biosynthesis isoprene rule due to the presence of an unprecedented acetamido motif directly connected with the terpenoidal side chain. The δ-truxinate derivative was isolated from Clausena species for the first time. Compound 1 showed high selectivity for the MAO-B isoenzyme and inhibitory activity in the nanomolar range. Putative biosynthesis pathways toward 1 and 2 are proposed.

Ten new formyl-phloroglucinol–terpene meroterpenoids, eucalypglobulusals A–J (1–10), and ten known analogues were isolated from Eucalyptus globulus fruits. The structures of 1–10 were determined by spectroscopic analysis, while their absolute configurations were established using calculated and experimental electronic circular dichroism (ECD) spectra. Eucalypglobulusal A was assigned as a new formyl-phloroglucinol–terpene meroterpenoid with a rearranged sesquiterpene skeleton, and an aldol condensation between C-3 and C-5 of the germacrene C moiety was proposed to be a key step in its putative biosynthetic pathway. Eucalypglobulusal F exhibited cytotoxicity against the human acute lymphoblastic cell line (CCRF-CEM) with an IC50 value of 3.3 μM, while eucalypglobulusal A, eucarobustol C, macrocarpal A, macrocarpal B, and macrocarpal D exhibited DNA topoisomerase I (Top1) inhibition. The compounds eucalypglobulusal A and macrocarpal A act as Top1 catalytic inhibitors and delay Top1 poison-mediated DNA doubl...

An unusual Daphniphyllum alkaloid, 2-deoxymacropodumine A (1), possessing an 11-membered macrolactone ring, was obtained from an extract of the stems of Daphniphyllum angustifolium. The structure of 1 was elucidated by 1D and 2D NMR spectroscopic methods and chemical calculations. Based on a comparison of the experimental and calculated NMR data, the structure of macropodumine A (2′), an analogue of 1, was also revised.

The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

Three new Myrioneuron alkaloids, myrifamines A-C (1-3), with unique skeletons were isolated from Myrioneuron faberi. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis, and the stereochemistry of the other two alkaloids was determined using a combination of ROESY experiments and calculated and experimental electronic circular dichroism spectra. Myrifamine C (3) is the first example of a symmetric dimer among the Myrioneuron alkaloids. Known alkaloids myrionamide (4) and schoberine (5) were also isolated, and experimental NMR and X-ray diffraction data suggest their structural revision. Compound 2 showed significant inhibitory activity toward the hepatitis C virus in vitro, with a therapeutic index (CC50/EC50) greater than 108.7.

Three indole alkaloid glycosides, strobilanthosides A-C (1-3), two known indole alkaloid glucosides (4 and 5), and five phenylethanoid glycosides (8-10) were isolated from the aerial parts of Strobilanthes cusia. The structures of the new compounds were elucidated by spectrometric analysis, and the absolute configurations of 1 and 2 were established by ECD spectrocsopy. N'-β-d-Glucopyranosylindirubin (5) showed weak antibacterial activity (MIC 62.5-125 μM) against Staphylococcus aureus.

Seven new compounds, including a eupodienone-type lignan (1), a dibenzocyclooctadiene-type lignan (2), three tetrahydrofuran-type lignans (3-5), and two 1-phenyl-butyl benzoates (6, 7), together with six known compounds, were isolated from the mature carpels of Manglietiastrum sinicum. The structures of new compounds 1-7 were defined by spectroscopic techniques, and the absolute configuration of manglisin A (1) was determined by X-ray crystallography. Compounds 1-4 exhibited moderate antimicrobial activities (MIC values: 0.016-0.14 mu M) against Staphylococcus aureus, MRSA 82(#), MESA 92(#), NLRSA 98(#), and MRSA 331(#). Compounds 2 and 3 showed weak cytotoxic activity against five human tumor cell lines.

Phytochemical investigation of the latex of Antiaris toxicaria resulted in the isolation of 15 new [antiarosides J-X (1-15)] and 17 known cardiac glycosides. The effects of the cardiac glycosides on apoptosis and the expression of orphan nuclear receptor Nur77 were examined in human NIH-H460 lung cancer cells. Several of the cardiac glycosides induced apoptosis in lung cancer cells, which was accompanied by induction of Nur77 protein expression. Treatment of cancer cells with the cardiac glycosides resulted in translocation of the Nur77 protein from the nucleus to the cytoplasm and subsequent targeting to mitochondria. The results show that the cardiac glycosides exert their apoptotic effect through the Nur77-dependent apoptotic pathway.

Myritonines A–C (1–3), three new alkaloids bearing an unprecedented heterohexacyclic skeleton, were isolated from Myrioneuron tonkinensis. Their structures were determined by a combination of spectroscopic data and single-crystal X-ray diffraction analysis. Compound 3 represents the first Myrioneuron alkaloid featuring a unique trans-decahydroquinoline motif and was also found to possess a rare cyano functionality. Compounds 1 and 2 showed inhibition against the hepatitis C virus in vitro.

Ten new yuzurine-type Daphniphyllum alkaloids, daphmacromines A-J (1-10), along with seven known alkaloids were isolated from the leaves and stems of Daphniphyllum macropodum. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry, and the structure of 1 was confirmed by single-crystal X-ray diffraction. The pesticidal and cytotoxic activities of the isolated alkaloids were evaluated in vitro against brine shrimp (Artemia salina) and five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480), respectively. This study also suggested structural revisions of oxodaphnigracine, oxodaphnigraciline, and epioxodaphnigraciline.

Trigoflavidols A (1) and B (2), tetranorditerpenoid dimers possessing a rearrangement skeleton with a spiroketal core moiety, and trigoflavidol C (3), a hexanorditerpenoid, have been isolated from Trigonostemon flavidus along with two known compounds. Compounds 1 and 2 showed moderate antimicrobial activities (MIC values: 3.12-6.25 μg/mL) against Staphylococcus aureus, 8(#)MRSA, and 82(#)MRSA, and 1, 2, and 5 showed weak activities (IC(50) values: 3.75-28.99 μM) against various human tumor cell lines.

Lycorine is a benzylphenethylamine-type alkaloid member of the Amaryllidaceae family. A lycorine derivative, HLY78, was previously identified as a new Wnt/β-catenin signaling pathway agonist that targets the DAX domain of axin. Herein, the structural optimization of HLY78 and analyses of the structure-activity relationships of lycorine-derived phenanthridine derivatives as agonists of the Wnt/β-catenin signaling pathway are presented. This research suggests that triazole groups are important pharmacophores for Wnt activation; triazole groups at C-8 and C-9 of phenanthridine compounds markedly enhanced Wnt activation. A C-11-C-12 single bond is also important for Wnt activation. On the basis of these findings, two Wnt agonists were designed and synthesized. The results for these agonists indicated that the combination of a 4-ethyldihydrophenanthridine skeleton and a triazole substituent improves Wnt activation. These compounds may be useful in further pharmacological or biological studies.

Eight new limonoids with four different structural frameworks, including gedunin (1, 2), havanensin (3, 4), mexicanolide (5, 6), and methyl angolensate types (7, 8), together with six known limonoids, were isolated from the leaves of Cipadessa baccifera. Compounds 2 and 5 exhibited moderate cytotoxicity against the HL-60 cell line with an IC(50) value of 20 microM.

Three new isopimarane diterpenoids, trogopteroids A-C (1-3), our new aromatic diterpenoids, trogopteroids D-G (4-7), and 12 known diterpenoids were isolated from the feces of Trogopterus xanthipes. Their structures were identified using spectroscopic methods. The relative configuration of 1 was confirmed by quantum calculations. Compound 1 represents the first example of a norisopimarane diterpenoid with an 8 alpha,15 alpha-olide ring. With the exception of compound 14, all diterpenoids were evaluated for cytotoxicity against seven human tumor cell lines.

Seven new neoclerodane diterpenoids, scutebatas A-G (1-7), have been isolated front Scutellaria barbata. Compounds 1-3 possess a rare alpha-hydroxy group in their alpha,beta-unsaturated lactone rings. Their Structures Were elucidated by spectroscopic analysis, and the relative configuration of scutebata A was deduced using ROESY data and the computational DFT method. Compounds 1, 2, 4, 5, and 6 were evaluated for in vitro cytotoxicity against six human cancer cell lines: HL-60, SMMC-7721, A-549, SK-BR-3, CACO-2, and PANC-1. Scutebata A (1) showed weak cytotoxicity against SK-BR-3 with an IC(50) value of 15.2 mu M.

Seven known and six new tetranortriterpenoids, cineracipadesins A-F (1-6), were isolated from the leaves of Cipadessa cinerascens. Compound 1 has a mexicanolide-type structural skeleton with a rare 9 alpha, 11 alpha-epoxide ring; compound 2 has a methyl angolensate-type structure with 9,11-dihydroxy groups, representing the first example of a precursor of a trijugin-type limonoid; and 3 is the first reported methyl angolensate-type limonoid with a ketone group at ring C. Their structures were determined with extensive spectroscopic analysis. X-ray crystallography confirmed the structure of 1. The ability of compounds 1-7 to inhibit the growth of the P-388 murine leukemia cell line was evaluated.

Eight new resin glycosides, pescapreins X-XVII (1-8), were isolated from a lipophilic fraction of an ethanol extract of the entire plant of beach morning glory, Ipomoea pes-caprae. Their structures were elucidated by spectroscopic data analysis and by chemical transformation. These compounds were evaluated biologically in terms of cancer cell line cytotoxicity, antibacterial and antifungal activity, and effects on the mu-opioid receptor.

Four new Daphniphyllum alkaloids, daphnioldhanines H-K ( 1- 4), along with 34 known alkaloids, were isolated from Daphniphyllum oldhami. The known alkaloid dehydrodaphnigraciline ( 5) is now reported as a natural product. Their structures were elucidated by spectroscopic methods, especially 2D NMR techniques. The effects against platelet aggregation of compounds 1, 3, and 5 were evaluated, and 3 showed stronger activity against platelet aggregation induced by PAF. This is the first report of quinolizidine alkaloids from the genus Daphniphyllum.

Four new trijugin-type limonoids, cipatrijugins A-D (1-4), together with the known cipadesin A (5), were isolated from the leaves of Cipadessa cinerascens, and their structures were elucidated on the basis of spectroscopic and computational methods. The ability of compounds 1-5 to inhibit the growth of the A549 and K562 tumor cell lines was evaluated.

Four new Daphniphyllum alkaloids, daphnimacropodines A-D (1-4), together with three known ones, daphnilactone B and daphnezomines H and I, were isolated from the fruits of Daphniphyllum macropodum. Their structures were determined by spectroscopic methods, especially 2D NMR techniques.

Six new apiosyl-(1--6)-glucosyl isoflavones (1-6) and four known ones were isolated from the stems of Glycosmis pentaphylla. The structures of the new glycosides are 3',7-dihydroxy-4',5,6-trimethoxyisoflavone 7-O-(5-O-trans-p-coumaroyl)-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (1), 2',7-dihydroxy-4',5',5,6-tetramethoxyisoflavone 7-O-(5-O-trans-p-coumaroyl)-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (2), 2',7-dihydroxy-4',5',5,6-tetramethoxyisoflavone 7-O-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (3), 7-hydroxy-4',8-dimethoxyisoflavone 7-O-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (4), 7-hydroxy-4',6-dimethoxyisoflavone 7-O-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (5), and 4',5-dihydroxy-3',7-dimethoxyisoflavone 4'-O-beta-D-apiofuranosyl-(1--6)-beta-D-glucopyranoside (6). Their structures were established primarily by NMR experiments and chemical methods.

Two new bisindole alkaloids, angustifonines A (1) and B (2), comprising the union of a rearranged monoterpenoid quinoline and an aspidospermine alkaloid, as well as 27 known indole alkaloids were isolated from the twigs and leaves of Bousigonia angustifolia. Their structures and absolute configurations were elucidated by a combination of MS, NMR, and computational methods. Angustifonines A and B exhibited cytotoxicity against various human cancer cell lines with IC50 values of 2.71-16.22 mu M. A possible biosynthesis pathway toward the new bisindole alkaloids 1 and 2 is presented.

Eight new aphanamixoid-type aphanamixoids (C-J, 1-8) and six new prieurianin-type limonoids, aphanamixoids K P (9-14), along with 10 known terpenoids were isolated from Aphanamixis polystachya, and their structures were established by spectroscopic data analysis. Among the new limonoids, 13 compounds exhibited antifeedant activity against the generalist Helicoverpa armigera, a plant-feeding insect, at various concentration levels. In particular, compounds 1, 4, and 5 showed potent activities with EC50 values of 0.017, 0.008, and 0.012 mu mol/cm(2), respectively. On the basis of a preliminary structure activity relationship analysis, some potential active sites in the aphanamixoid-type limonoid molecules are proposed.

Eleven new limonoids, turrapubins A-K (1-11), and three new triterpenoids (12-14), along with 14 known compounds, were isolated from the twigs of Turraea pubescens. The structures of 1-14 were elucidated on the basis of NMR and MS analysis. Compounds 12, 16, 18, and 19 exhibited inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. In addition, compounds 2, 11, 18, and 26 exhibited inhibitory activities against brine shrimp larvae (Artemia salina) at 100 ppm with the corrected mortality ranging from 81.7% to 100%.

Eight new limonoids, khayseneganins A-H (1-8), and 31 known limonoids were isolated from the leaves and twigs of Khaya senegalensis. The structures of the new compounds were elucidated by 2D-NMR spectroscopy and mass spectrometry, and the absolute configuration of 1 was determined by the CD exciton chirality method. Compounds 9, 10, 12, and 15 showed antimicrobial activities against Pseudomonas aeruginosa, MRSA 92(#), and MRSA 98(#), all with a MIC value of 12.5 mu g/mL.

Two new C-21 steroidal glycoside epimers, paniculatumosides A and B (1 and 2), based on a 13,14:14,15-disecopregnane-type skeleton, with neocynapanogenin B (3) and neocynapanogenin C (4) as two new aglycons, were isolated from the roots of Cynanchum paniculatum. Their structures were determined by spectral data interpretation.

Two new carbazole alkaloids named murrayanine (1) and 8,8' '-biskoenigine (2) were isolated from Murraya koenigii. The structure elucidations for 1 and 2 were carried out on the basis of 1D and 2D NMR experiments. Compound 1 was a novel carbazole alkaloid with a rare phenylpropanyl substitution. Compound 2 was a symmetrical dimer of the carbazole alkaloid koenigine and showed antiosteoporotic activity in the CAT-B model with IC(50) 1.3 microg/mL. The synthesis of 2 from koenigine was carried out through oxidative coupling using a solid state reaction.

Two new degraded diterpenoids, trigohowilols A (1) and B (2), four new heterodimers, trigohowilols C-F (3-6), one new homodimer, trigohowilol G (7), and three known degraded diterpenoids (8-10) were isolated from the methanol extract of the stems of Trigonostemon howii. Compounds 1-7 were evaluated for their cytotoxic activity against five human tumor cell lines by an MTT assay, and trigohowilols E (5) and F (6) exhibited inhibitory activity with IC50 values ranging from 2.33 to 12.57 mu M Moreover, compounds 1-6 showed weak antimicrobial activities (MIC values: 6.25-25 mu g/mL) against Staphylococcus aureus, Pseudomonas aeruginosa, MRSA 92(#), and MRSA 98(#) using a 2-fold dilution method.

Five new triterpenoids, caloncobic acids A and B (1 and 2), caloncobalactones A and B (3 and 4), and glaucalactone (5), along with the known compounds 3 beta,21 beta-dihydroxy-30-nor-(D:A)-friedo-olean-20(29)-en-27-oic acid (6) and acetyltrichadenic acid B (7), were isolated from the leaves of Caloncoba glauca. The structures of 1-5 were elucidated using spectroscopic methods. Compounds 1-7 were evaluated for their inhibitory activities against two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1 and 11 beta-HSD2). Compounds 1 and 2 exhibited strong inhibitory activities against mouse (EC50 132 and 13 nM) and human (EC50 105 and 72 nM) 11 beta-HSD1.

Two ring A-rearranged clerodane diterpenes named dunniana acids A (1) and B (2) were isolated from the aerial parts of Clausena dunniana. The structures of 1 and 2 were determined using spectral methods.