Three new C19-diterpenoid alkaloids from Delphinium tianshanicum W. T. Wang

Three new C₁₉-diterpenoid alkaloids, tianshanisine (1), tianshanine (2) and tianshanidine (3), together with six known C₁₉-diterpenoid alkaloids (4–9) were isolated from the whole herb of Delphinium tianshanicum W. T. Wang. Their structures were established on the basis of spectroscopic analyses, including HR-ESI-MS and 1D and 2D NMR.     

Five new diterpenoid alkaloids from Aconitum sczukinii Turcz.

Ten diterpenoid alkaloids, including five new ones, sczukiniline A–E (1-5), were isolated from the root of Aconitum sczukinii. Their structures were elucidated based on the interpretation of spectroscopic data (HRESI-MS, IR, 1D- and 2D-NMR). Among the five new diterpenoid alkaloids, 1-3 are hetidine-type C₂₀-diterpenoid alkaloids, while compounds 4 and 5 are lycoctonine-type C₁₉-diterpenoid alkaloids. Noteworthily, sczukiniline A (1) features a novel ester group between C-12 and C-14, forming a D ring containing a lactone structure, resulting in a new skeleton of hetidine-type C₂₀-diterpenoid alkaloid.     

Unusual C19-diterpenoid alkaloids from Aconitum vilmorinianum var. patentipilum

Three new C₁₉-diterpenoid alkaloids vilmotenitines A-C (1-3), together with seven known ones, vilmorine D (4), talatizidine (5), isotalatizidine (6), vilmorrianine B (7), vilmorrianine D (8), talatizamine (9), 8-deacetyl-yunaconitine (10), were isolated from Aconitum vilmorinianum var. patentipilum. Vilmotenitines A (1) and B (2) are the second natural occurrences of C₁₉-diterpenoid alkaloids with a unique rearranged six-membered B ring formed by the C₍₈₎–C₍₁₀₎ linkage.     

Cytotoxic azaphilone alkaloids from Chaetomium globosum TY1

Three novel azaphilone alkaloids, namely chaetomugilides A–C (1–3), together with three related compounds (4–6) were isolated from the methanol extract of Chaetomium globosum TY1, an endophytic fungus isolated from Ginkgo biloba. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The isolated compounds exhibited highly cytotoxic activities against human cancer cell line HePG2 with the IC₅₀ values range from 1.7 to 53.4 μM.     

Alkaloids from the mangrove endophytic fungus Diaporthe phaseolorum SKS019

Six new alkaloids including four new chromeno[3,2-c]pyridines, diaporphasines A-D (1–4), and two new isoindolinones, meyeroguillines C and D (6–7), as well as three known compounds meyeroguilline A (5), 5-deoxybostrycoidin (8), and fusaristatin A (9), were isolated from an endophytic fungus Diaporthe phaseolorum SKS019. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Compounds 1–9 are alkaloid components reported for the first time from the Diaporthe sp., and diaporphasines A-D (1–4) are the third examples of alkaloids possessing the unique chromeno[3,2-c]pyridine nucleus. All isolated compounds 1–9 were evaluated for their cytotoxic activity in vitro using MDA-MB-435, HepG2, MCF10A, HCT116, and NCI-H460 human cell lines. Compound 8 exhibited cytotoxicity against MDA-MB-435 and NCI-H460 human cancer cell lines with IC₅₀ values of 5.32 and 6.57 μM, respectively, and compound 9 showed growth-inhibitory activity against MDA-MB-435 human cancer cell line with IC₅₀ value of 8.15 μM.     

Glycopentanolones A-D,four new geranylated quinolone alkaloids from Glycosmis pentaphylla

The ethanolic extract obtained from the stems of Glycosmis pentaphylla was found to suppress antigen-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. Four new geranylated 2-quinolone alkaloids, named glycopentanolones A–D (1–4), and 12 known metabolites (5–16) were isolated from the ethanolic extract from the stems of G. pentaphylla using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, and HRESI-MS. The inhibitory effects of the isolated constituents on β-hexosaminidase release from RBL-2H3 cells were examined, and compounds 1, 5, 8 and 11 exhibited potent inhibitory activity with IC₅₀ values between 0.05 and 4.28 μM.     

Five new alkaloids from Aconitum apetalum (Ranunculaceae)

Twenty-one alkaloids, including five new ones, acoapetaldines A–E (1–5), were isolated from the whole plants of Aconitum apetalum. Among them, 1 is an aconitine-type diterpenoid alkaloid, 2 and 3 are aporphine alkaloids and 4 and 5 are napelline-type diterpenoid alkaloids. The structures of the new alkaloids were elucidated by spectroscopic data analysis and that of acoapetaldine D (4) was confirmed by single crystal X-ray crystallography. Acoapetaldine A (1) and aconorine (12) exhibited moderate anti-tobacco mosaic virus (anti-TMV) activity, while corydine (15) displayed moderate antimicrobial activity against Pseudomonas aeruginosa.     

Taxonomic significance and antitumor activity of alkaloids from Clausena lansium Lour. Skeels (Rutaceae)

Phytochemical analysis of isolates from the aerial parts of Clausena lansium Lour. Skeels (Rutaceae) led to the identification of 14 alkaloids, including two indole alkaloids (1 and 2), one quinoline alkaloid (3), two pyridine alkaloids (4 and 5), four carbazole alkaloids (6–9) and five amides alkaloids (10–14). The phytochemical structures of the alkaloids were established by means of NMR and MS spectral analyses. Compounds (4, 5, 14) were three new natural products, while 1–3 and 10 were firstly reported from the genus Clausena and 8 and 9 were isolated from this species for the first time. The chemotaxonomic significance of these isolated alkaloids has also been discussed. All the isolated alkaloids were tested for their cytotoxic activity against Hela cancer cell line. Among them, four carbazole alkaloids 6–9 exhibited weak cytotoxicity with IC₅₀ values ranging from 69.31 to 138.32 μM.     

Tetrahydro-β-Carboline alkaloids from Carthamus tinctorius L. with tyrosinase inhibitory activity

Phytochemical research on the dry flower of Carthamus tinctorius L. led to the isolation of two new epimeric tetrahydro-β-carboline alkaloids (1 and 2), together with three known analogues (3–5). Their planar structures were determined by comprehensive 1D, 2D-NMR, and HR-ESI–MS spectroscopic data analyses. The absolute configurations of alkaloids 1 and 2 were assigned by comparing their experimental electronic circular dichroism (ECD) curves with the calculated ECD data. To investigate their impact on melanogenesis, all of the alkaloids isolated were tested for their tyrosinase inhibitory activity and alkaloid 4 was found to inhibit tyrosinase with an IC₅₀ value of 0.17 mM, compared with 0.18 mM for arbutin. The putative binding interactions between the compounds and tyrosine were studied by molecular docking to provide an explanation for their inhibitory activities, and the results obtained indicated that hydrophobic interactions played a very significant role in the combination.     

New furanopyridine alkaloids from the leaves of Glycosmis pentaphylla

Three new furanopyridine alkaloids, namely glypenfurans A–C (1–3), were isolated from the leaves of Glycosmis pentaphylla together with six known furoquinoline alkaloids. Their structures were determined by extensive spectral analysis (UV, IR, MS, 1D and 2D NMR).     

Chemical constituents of Gardneria ovata wall

A phytochemical investigation on the aerial parts of Gardneria ovata Wall resulted in the isolation and identification of 14 compounds, including three gardneria glycoalkaloids (1–2 and 6), seven gardneria alkaloids (3–5 and 7–10), and four oxindole alkaloids (11–14). The structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS together with 1D and 2D NMR experiments. Compounds 1–2 and 11–14 are the first time reported from of G. ovate, while the compounds 3–4, 6, and 8 are also the characteristic secondary metabolites of the title plant. The chemotaxonomic significance and distribution of these monoterpenoid indole alkaloids in Gardneria genus are discussed.     

Phytochemical and chemotaxonomic study on Dictamnus angustifolius G. Don ex Sweet (Rutaceae)

A phytochemical investigation of Dictamnus angustifolius led to the isolation of 14 compounds, including six furoquinoline alkaloids (1–6), two sesquiterpenoids (7, 8) and six flavonoids (9–14). The structures of these compounds were identified by spectroscopic methods and a comparison of their data with those reported in the literature. This is the first report of three furoquinoline alkaloids 1–3 and six flavonoids 9–14 from the genus Dictamnus and the first isolation of compounds 4–8 from D. angustifolius. The chemotaxonomic significance of furoquinoline alkaloids and sesquiterpenoids has also been summarized.     

Oxytrofalcatins A–F,N-benzoylindole analogues from the roots of Oxytropis falcata (Leguminosae)

Indole alkaloids, oxytrofalcatins A–F (1–6), together with five other known alkaloids (7–11), were isolated from the roots of Oxytropis falcata. Their structures were elucidated by comprehensive spectroscopic analyses, including using 1D and 2D NMR spectroscopy and mass spectrometry. This is the first report of N-benzoylindoles from a natural source. Compounds 1–6 lacked significant cytotoxicity against SGC-7901 and HL-60 tumor cell lines.     

Isolation,leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis

Leishmaniasis is one of the most important neglected tropical diseases (NTDs) that are especially common among low-income populations in developing regions of Africa, Asia, and the Americas. Many natural products, particularly alkaloids, have been reported to have inhibitory activity against arginase, the key enzyme in the pathology caused by Leishmania sp. In this way, piperidine alkaloids (–)-cassine (1), (–)-spectaline (2), (–)-3-O-acetylcassine (3), and (–)-3-O-acetylspectaline (4) were isolated from Senna spectabilis flowers. These compounds (1/2 and 3/4) initially present as homologous mixtures were separated by high performance liquid chromatography and evaluated against the promastigote phase of Leishmania amazonensis. In addition, molecular docking simulations were implemented in order to probe the binding modes of the ligands 1–4 to the amino acids in the active site of L. amazonensis arginase. Alkaloid 2 (IC₅₀ 15.81?μg?mL^?1) was the most effective against L. amazonensis. Compounds 2 and 4, with larger side chain, were more effective against the parasite than compounds 1 and 3. The cell viability test on Vero cells revealed that compound 2 (CC₅₀ 66.67?μg?mL^?1) was the most toxic. The acetyl group in the 3-O position of the parent structures reduced the leishmanicidal activity and the toxicity of the alkaloids. Further, molecular docking suggested that Asn143 is essential for arginase to interact with (–)-spectaline-derived compounds, which agreed with the IC₅₀ measurements. Our findings revealed that S. spectabilis is an important source of piperidine alkaloids with leishmanicidal activity. Moreover, the natural compound 3 has been isolated for the first time. Experimental investigation combined with theoretical study advances knowledge about the enzyme binding site mode of interaction and contributes to the design of new bioactive drugs against Leishmania infection.     

Five new C19-diterpenoid alkaloids from Aconitum carmichaeli

Five new aconitine-type C₁₉-diterpenoid alkaloids, namely, carmichaenine A–E (1–5), and six known diterpenoid alkaloids, namely, 14-benzoylneoline (6), neoline (7), 10-hydroxyneoline (8), neolinine (9), songoramine (10), and songorine (11), were isolated from the aerial parts of Aconitum carmichaeli. Their structures were determined by extensive spectroscopic methods, especially 2D NMR analyses. Compounds 8 and 9 were isolated for the first time from A. carmichaeli.     

Monoterpenoid indole alkaloids from Kopsia hainanensis Tsiang

A phytochemical investigation on the twigs and leaves of Kopsia hainanensis Tsiang resulted in the isolation and identification of 18 alkaloids, including two sarpagine type alkaloids (1 and 2), five eburnane type alkaloids (3–7), three aspidofractinine type alkaloids (8–10), one vincadine type alkaloid (11), three akuammiline type alkaloids (12–13 and 15), one corynanthean type alkaloid (14), two ajmalicine-like type alkaloids (16 and 17), and one aspidospermine type alkaloid (18). The new structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR experiments. Compounds 1–2, 4–5, 7, and 10–17 are herein reported for the first time from this plant, while the compounds 1, 2, 7, and 12–17 have not been previously recorded in the Kopsia genus. The chemotaxonomic significance and distribution of these monoterpenoid indole alkaloids in Kopsia genus are discussed.     

Pregnane alkaloids from Sarcococca ruscifolia and their cytotoxic activity

Six pregnane alkaloids were isolated from the root of Sarcococca ruscifolia. The structures of three new alkaloids, namely, sarcorucinine E–G (1–3), were elucidated using spectroscopic methods, while three known alkaloids, namely, epipachysamine D, pachysamine M, and sarcovagine D, were identified by comparing their spectral data with those of the compounds reported earlier. All compounds were evaluated for their inhibitory activities against multiple types of cancer cells.     

Anti-inflammatory and antiproliferative prenylated carbazole alkaloids from Clausena vestita

Twelve prenylated carbazole alkaloids, containing a novel prenylated carbazole alkaloid, named as clausevestine (1), and 11 known prenylated carbazole alkaloids (2–12), were isolated and identified from the stems and leaves of Clausena vestita, which is a Chinese endemic plant. The chemical structure of 1 was established by means of comprehensive spectroscopic data analyses and the known compounds were determined via comparing their NMR and MS data as well as optical rotation values with those reported in literature. Especially, clausevestine (1) is an unusual prenylated carbazole alkaloid possessing an unprecedented carbon skeleton holding 20 carbon atoms. The anti-inflammatory effects and antiproliferative activities of those isolated prenylated carbazole alkaloids were tested. Prenylated carbazole alkaloids 1–12 displayed remarkable inhibitory effects on NO (nitric oxide) production with IC₅₀ values equivalent to that of the positive control (hydrocortisone). Meanwhile, prenylated carbazole alkaloids 1–12 exhibited remarkable antiproliferative activities against diverse human cancer cell lines in vitro holding the IC₅₀ values ranging from 0.32 ± 0.04 to 18.76 ± 0.18 µM. These findings indicate that these prenylated carbazole alkaloids possessing remarkable anti-inflammatory effects and antiproliferative activities could be meaningful to the discovery of new anti-inflammatory and anti-tumor candidate drugs.     

Chemical constituents of Melodinus hemsleyanus diels

Phytochemical investigation on the aerial parts of Melodinus hemsleyanus diels (Jahrb, Syst, 1995) led to the isolation and identification of 27 compounds, including fifteen aspidosperma-type alkaloids (1–15), four quinoline-type alkaloids (16–19), three quebrachamine-type alkaloids (20–22), and five eburna-type alkaloids (23–27). The structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR experiments. Compounds 1–2, 6, 10, 12, 13, 15, 16 and 20–27 are herein reported for the first time from the studied plant, while the compounds 1–2 and 21 have not previously been recorded in the genus Melodinus. The aspidosperma-type monoterpenoid indole alkaloids in M. hemsleyanus could serve as chemotaxonomic markers.     

Alstiphyllanines E–H,picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

Three new picraline-type alkaloids, alstiphyllanines E–G (1–3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5–20). Structures and stereochemistry of 1–4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na⁺-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A series of a hydroxy substituted derivatives 21–28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity. 10-Methoxy-N(1)-methylburnamine-17-O-veratrate (6) exhibited potent inhibitory activity, suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity. Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.