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.     

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.     

Natural indole butyrylcholinesterase inhibitors from Nauclea officinalis

Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC₅₀ values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.     

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.     

Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

Chemical analysis of a specimen of the sponge Ianthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3′-deimino-3′-oxoaplysinopsin (6), 8Z-3′-deimino-3′-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards α3 over α1 GlyR, while tubastrindole B (9) exhibited a bias towards α1 over α3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of α1 GlyR, with no effect on α3 GlyR—a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1–9 were further supported by the synthesis of a number of structurally related indole alkaloids.     

Melohenryines A and B,two new indole alkaloids from Melodinus henryi

Two new monoterpenoid indole alkaloids, melohenryines A and B (1 and 2), along with six known indole alkaloids, were isolated from the twigs and leaves of Melodinus henryi. Structures of the new alkaloids were established by extensive spectroscopic techniques including NMR spectroscopy and mass spectrometry. Melohenryine A (1) represents the first example of monoterpenoid indole alkaloids characterized an ester carbonyl group at C-19 position. All of the new compounds were evaluated for in vitro cytotoxicity against several human cancer cell lines.     

Phytochemical constituents from Neolamarckia cadamba (Roxb.) Bosser

Phytochemical study on Neolamarckia cadamba (Roxb.) Bosser has yielded ten indole alkaloids, neolarmarckine A-E (1–5), cadamine (6), 3β-isodihydrocadambine (7), angustine (8) and naulafine (9) and harmane (10). The structural elucidation of all the compounds were conducted based on the thorough analysis of spectroscopic data and comparison with reported data. The chemotaxonomic significance of all these compounds were summarized. Among all the indole alkaloids, compound 3–5 were new compounds and isolated from Neolamarckia cadamba (Roxb.) Bosser for the first time. Compounds 1 and 2 were only found in Neolamarckia species while compounds 6 and 7 were only isolated from the family of Rubiaceace. Besides, compound 8 has been found in six genera of Rubiaceae and two genera of Apocynaceae while compound 9 was isolated from Neolamarkia species for the first time. Compound 10 can be found in many genera of Rubiaceae and also more than ten families such as Zygophyllaceae, Cyperaceae, Passifloraceae, Bignoniaceae, Sapotaceae, Elaeagnaceae, Leguminosae, Loganiaceae, Apocynaceae, Combretaceae, Chenopodiaceae, Commelinaceae and Polygalaceae.     

Discovery of indole alkaloids with cannabinoid CB1 receptor antagonistic activity

Three indole alkaloids, voacamine (1), 3,6-oxidovoacangine (2), and a new alkaloid, 5-hydroxy-3,6-oxidovoacangine (3), isolated from Voacanga africana were found to exhibit potent cannabinoid CB1 receptor antagonistic activity. This is the first example of CB1 antagonists derived from natural alkaloids.     

Phytochemical and chemotaxonomic study on Evodia rutaecarpa var. officinalis

Phytochemical investigations of the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth. var. of officinalis (Dode) Huang (family Rutaceae) led to the isolation of twenty compounds, including eight quinolone alkaloids (1–8), seven indole quinazoline alkaloids (9–15), two limonoids (16–17) and three sterols (18–20). The chemical structures of these compounds were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Notably, seven compounds (1, 3, 7, 11 and 13–15) were reported from this species for the first time, and the chemotaxonomic significance of these compounds was discussed.     

Cytotoxic monoterpenoid indole alkaloids from the leaves and twigs of Tabernaemontana bovina

Phytochemical investigation of the leaves and twigs of Tabernaemontana bovina led to the isolation of 10 monoterpenoid indole alkaloids, including two new taberbovinines A (1) and B (2) along with eight known analogs: mehranine (3), 14α,15β-dihydroxy-N-methylaspidospermidine (4), (16S*)− 15-epi-E-isositsirikine (5), (16R*)− 15-epi-E-isositsirikine (6), 16 R*-19,20-E-isositsirikine acetate (7), hecubine (8), voafinidine (9), and voacangarine (10). Taberbovinine B (2) represents the first case of an unusual ring C/D cleavage among the natural Corynanthe-type alkaloids. Compounds 2 and 8 exhibited weak cytotoxicity against five human cancer cell lines, including SK-LU-1, HepG2, MCF-7, SK-Mel-2, and LNCaP, with IC₅₀ values ranging from 42.9 to 66.3 μM, whereas compounds 4 − 6 and 9 were cytotoxic toward MCF-7, SK-LU-1 and LNCaP cells, with IC₅₀ values in a range of 51.6–93.3 μM.     

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.     

Bioactive monoterpene indole alkaloids from Nauclea officinalis

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC₅₀ values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.     

Monoterpenoid indole alkaloids from Palicourea crocea

A new monoterpenoid indole alkaloid N-oxide, 3,4-dihydro-1-(1-β-d-glucopyranosyloxy-1,4a,5,7a-tetrahydro-4-methoxycarbonylcyclopenta[c]pyran-7-yl)-β-carboline-N²-oxide (3) and two known monoterpenoid indole alkaloids, croceaine A (1) and psychollatine (2), were isolated from Palicourea crocea (Rubiaceae) from Trinidad. The structures of 1–3 were determined on the basis of spectral and other physical data. Compounds 1 and 2 were previously isolated from plants of different genera viz. Palicourea crocea and Psychotria umbellata, respectively, both collected in Brazil. The results support the proposal that the genus Palicourea and the subgenus Heteropsychotria should be combined into a single genus.     

Induction of apoptosis in HuH-7 cancer cells by monoterpene and β-carboline indole alkaloids isolated from the leaves of Tabernaemontana elegans

Three known (1–3) and a novel (4) monoterpene indole alkaloids have been isolated from the methanol extract of leaves of Tabernaemontana elegans and their structures were elucidated by a series of spectroscopic experiments, involving NMR, MS, UV, and IR techniques. The isolated monoterpene indole alkaloids along with previously described β-carbolines (5–7) from the same specimen were studied for their apoptosis induction activity in human hepatoma HuH-7 cells. Methodology for apoptosis induction studies included cell viability assays, nuclear morphology assessments, and general caspase-3-like activity assays. The monoterpene indole alkaloids, tabernaemontanine (1) and vobasine (3) showed the most promising apoptosis induction profile in HuH-7 cells.     

Phytochemicals isolated from the root bark of Sarcocephalus latifolius (Sm.) E.A.Bruce

Phytochemical investigation of the root bark of Sarcocephalus latifolius resulted in isolation and identification of eight compounds, including triterpenoid glycosides (1-4), ethyl glucoside (5), monoterpene indole alkaloids (6-7), and sterol (8). The structure elucidation of isolated compounds was achieved on the basis of NMR and mass spectral data. Compounds 2-5 were isolated for the first time from this genus and their chemotaxonomic significance was discussed.     

Chemical constituents from Melodinus cochinchinensis (Lour.) Merr. and their chemotaxonomic significance

A phytochemical investigation on the twigs and leaves of Melodinus cochinchinensis (Lour.) Merr. resulted in the isolation and identification of 22 compounds, including seven sesamin-type lignans (1–7), three pentacyclic triterpenes (8–10), one anthraquinone (11), one flavanone (12), two phenolic compounds (13 and 14), five aspidosperma-type indole alkaloids (15–19), and three eburnan-type indole alkaloids (20–22). The structures of these compounds were elucidated by means of spectroscopic analysis, including HREIMS together with 1D and 2D NMR experiments, and comparison with reported data. Among them, compounds 1/4, 2/5, and 3/6 are three pairs epimers at C-7''. Compounds 1–6, 8 and 11 were firstly isolated from the family Apocynaceae, whereas 17 was isolated from Melodinus species for the first time. Compound 8 was only found in Juglans hopeiensis, while 11 was only found in roots of Rubia cordifolia. Compounds 1–6, 8, 11 and 15–22 could be considered as chemotaxonomic markers for M. cochinchinensis. Furthermore, the chemotaxonomic significance and distribution of these isolates in Melodinus genus are discussed in detail.     

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.     

Alkaloids and monoterpenes from the leaves of Isatis tinctoria Linnaeus and their chemotaxonomic significance

Phytochemical investigation of the leaves of Isatis tinctoria Linnaeus led to the isolation of thirty compounds, including thirteen indole alkaloids (1–13), seven quinazolinone alkaloids (14–20), two quinoline alkaloids (21–22), one quindoline alkaloid (23), one simple amide alkaloid (24) and six monoterpenes (25–30). According to spectroscopic data analysis and comparison with the previously reported literature, their structures were elucidated. Among them, six compounds (12, 13, 17, and 22–24) have not been reported from the family Brassicaceae and eight compounds (3, 7, and 25–30) were isolated from the genus Isatis for the first time. Furthermore, the chemotaxonomic significance of isolated compounds has also been elaborated.     

Indole alkaloids from Ervatamia chinensis

Four vobasinyl–ibogan type bisindole alkaloids, ervachinines A–D (1–4), along with 12 known terpenoid indole alkaloids, were isolated from the whole plant of Ervatamia chinensis. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR, and the absolute configurations of 1–4 were determined by CD exciton chirality method. All of the compounds were evaluated for in vitro cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480. Bisindole alkaloids 1–6 exhibited inhibitory effects, with IC₅₀ values comparable to those of cisplatin.     

Alkaloids from the stem bark of Strychnos icaja

A comprehensive phytochemical study of the stem bark of Strychnos icaja was done for the first time and led to the isolation of two new monoindole alkaloids 15-hydroxyvomicine (1) and 12-methoxyicajine (2) along with 13 known alkaloids: the monoindoles N-methyl-sec-iso-pseudostrychnine (3), vomicine (4), icajine (5), 19,20-α-epoxy-12-methoxyicajine (6), 19,20-α-epoxy-12,15-dihydroxy-11-methoxyicajine (7), 19,20-α-epoxy-15-hydroxynovacine (8), 15-hydroxyicajine (9), 12-hydroxystrychnine (10), strychnine (11) and the tertiary bisindoles sungucine (12), isosungucine (13), strychnogucine C (14) and bisnordihydrotoxiferine (15). Apart from 10 and 11, the other alkaloids were isolated for the first time from the stem bark of this plant. The hemisynthetic derivative, N_b-chloromethosungucine (16) and the previously reported synthetic compound 3 were isolated from a natural source for the first time. Fractions and some isolated compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. The bisindole alkaloids were most active with IC₅₀ ranging from 0.72 to 3.41 μg/ml whilst the monomers 1 and 3 were slightly active (IC₅₀ 39.92 and 40.27 μg/ml respectively) and 6 inactive. The structures of the compounds were determined based on the analysis of their spectral data. The full ¹H and ¹³C NMR data of compounds 3, 6 and 7 are also reported in the present work for the first time.