Bisleuconothine A,an eburnane–aspidosperma bisindole alkaloid from Leuconotis griffithii

A new bisindole alkaloid, bisleuconothine A (1) consisting of an eburnane–aspidosperma type skeleton, was isolated from the bark of Leuconotis griffithii. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and X-ray analysis. Bisleuconothine A (1) showed cell growth inhibitory activity against various human cancer cell lines.     

Gardovatine,a novel Strychnos–Strychnos bisindole alkaloid with cytotoxicity from Gardneria oveta

Gardovatine (1), the first Strychnos–Strychnos alkaloid with a C₃/C₇ cleaved backbone, was isolated from twigs and leaves of Gardneria ovate, together with an analogue divarine (2). The structure was established by extensive spectroscopic methods. Both compounds showed potential cytotoxicities against five human cancer cell lines.     

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.     

(−)-Epilamprolobine and its N-oxide,lupin alkaloids from Sophora tomentosa

From the fresh leaves of Sophora tomentosa, three new lupin alkaloids, (?)-epilamprolobine, (+)-epilamprolobine N-oxide and 5-(3′-methoxycarbonylbutyroyl)aminomethyl-trans-quinolizidine N-oxide, have further been isolated along with (+)-matrine, (+)-matrine N-oxide, (+)-sophocarpine N-oxide, (?)-anagyrine, (?)- baptifoline, (?)-cytisine, (?)-N-methylcytisine, (?)-N-formylcytisine, (?)-N-acetylcytisine and (±)-ammodendrine. The absolute configurations of (+)-epilamprolobine N-oxide (1R:5R:6S) and (?)-epilamprolobine (5R:6S) have also been established by spectroscopic data and by comparison with synthetic (+)-epilamprolobine (5S:6R)derived from (?)-lupinine (5R:6R). (?)-Epilamprolobine is a diastereomer of (+)-lamprolobine (5R:6R) in Lamprolobium fruticosum and 5-(3′-methoxycarbonylbutyroyl) aminomethyl-trans-quinolizidine N-oxide is presumed to be an artefact. A biosynthetic pathway for the formation of (?)-epilamprolobine is also proposed.     

Alpneumines A–H,new anti-melanogenic indole alkaloids from Alstonia pneumatophora

Eight new indole alkaloids, alpneumines A–H (1–8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells.     

Venezuelines A–G,new phenoxazine-based alkaloids and aminophenols from Streptomyces venezuelae and the regulation of gene target Nur77

Five new phenoxazine-based alkaloids venezuelines A–E (1–5) and two new aminophenols venezuelines F–G (6–7), as well as three known analogues exfoliazone, chandrananimycin D and carboxyexfoliazone were isolated from the fermentation broth of the marine-derived bacterium Streptomyces venezuelae. The structures of new compounds were determined on the basis of extensive spectroscopic analysis. The cytotoxic activity of these compounds against a panel of tumor cell lines were tested, while the regulation of gene target Nur77 of 2 and exfoliazone (8) were evaluated.     

Ecliptamines A–D,four new guanidine alkaloids from Eclipta prostrata L.

Four structurally unique guanidine alkaloids ecliptamines A–D (1–4) and one known analog (5) were isolated from the aerial parts of Eclipta prostrata (Asteraceae). Their structures were elucidated on the basis of spectroscopic analyses and chemical methods. The inhibitory activities of 1, 2 and 5 were assayed with respect to cyclooxygenase-1 (COX-1) and -2 (COX-2). Compound 5 showed moderate inhibitory activities against COX-1 and -2 with IC₅₀ values of 3.0 × 10⁻³ M and 8.3 × 10⁻⁴ M, respectively, whereas aspirin as a positive control displayed the IC₅₀ values of 4.2 × 10⁻⁴ M (against COX-1) and 7.1 × 10⁻⁴ M (against COX-2).     

New β-carboline and indole alkaloids from Actinomycete Actinomadura sp. BCC 24717

Four new β-carbolines 1–4 and two new indoles 5–6 were isolated together with thirteen known compounds from actinomycete, Actinomadura BCC 24717. Structures of the new compounds, 1–6, were determined by NMR spectroscopic and MS spectrometric analyses. Compound 4 exhibited cytotoxicity to Vero cells and compound 6 showed antifungal activity with IC₅₀ 35.91 μg/mL and 41.97 μg/mL, respectively.     

Chromatographic profiling and identification of two new iridoid-indole alkaloids by UPLC–MS and HPLC-SPE-NMR analysis of an antimalarial extract from Nauclea pobeguinii

The total 80% EtOH extract of stem bark of Nauclea pobeguinii (Rubiaceae), which is active against uncomplicated falciparum malaria as shown in previous clinical studies, was analysed by means of UPLC–MS and HPLC-SPE-NMR. Apart from the main constituent, strictosamide, a series of minor constituents was identified, including two new iridoid-indole alkaloids, i.e. naucleidinic acid and 19-O-methyl-3,14-dihydroangustoline, together with 8 known iridoid-indole alkaloids, i.e. naucleidinal, magniflorine, naucleofficine D, two diastereoisomers of 3,14-dihydroangustoline, strictosidine, desoxycordifoline, 3α,5α-tetrahydrodeoxycordifoline lactam, and a phenol glycoside 3,4,5-trimethoxyphenol β-d-apiofuranosyl-(1-6)-β-d-glucopyranoside (kelampayoside A).     

Purpuroines A–J,halogenated alkaloids from the sponge Iotrochota purpurea with antibiotic activity and regulation of tyrosine kinases

Ten new halogenated alkaloids named purpuroines A–J (1–10), and a known analogue (11), were isolated from the marine sponge Iotrochota purpurea. Their structures were elucidated by extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses. The inhibitory activity of some compounds against a panel of human disease related fungi and bacteria are evaluated. Bioassay for the regulation of tyrosine kinases revealed compounds 1 and 4 possessing selective inhibition against the kinase LCK. Primary structure–activity relationship is discussed.     

Structure–activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids,and their tricyclic and bicyclic analogues

Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-β-carboline, showed the best in vitro activity, with an IC₅₀ value of 0.45 μM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI > 1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure–activity relationships are discussed and compared with related naturally occurring compounds.     

Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene–alkaloids and their anti-cancer evaluation

A facile synthesis of piperidine alkene–alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene–alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene–alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.     

Chrotacumines G–J,chromone alkaloids from Dysoxylum acutangulum with osteoclast differentiation inhibitory activity

Four new chromone alkaloids, chrotacumines G–J (1–4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.     

Dicorynamine and harmalan-N-oxide,two new β-carboline alkaloids from Dicorynia guianensis Amsh heartwood

The chemical investigations of Dicorynia guianensis heartwood led to the isolation of four new indole alkaloids for the first time in this plant. Compound (1) identified as spiroindolone 2′,3′,4′,9′-tetrahydrospiro [indoline-3,1′pyrido[3,4-b]-indol]-2-one, and compound (3) described as nitrone 1-methyl-4,9-dihydro-3H-pyrido [3,4-b] indole 2-oxide and were isolated for the first time as natural products. ABTS antioxidant activity guided their isolation.     

Ceratinadins A–C,new bromotyrosine alkaloids from an Okinawan marine sponge Pseudoceratina sp.

Three new bromotyrosine alkaloids, ceratinadins A–C (1–3), were isolated from an Okinawan marine sponge Pseudoceratina sp. and the structures of 1–3 were elucidated on the basis of spectroscopic data. Ceratinadin A (1) was a novel bromotyrosine alkaloid possessing an N-imidazolyl-quinolinone moiety. Ceratinadins A (1) and B (2) showed antifungal activity.     

Minor indolopyridoquinazoline alkaloids from Euxylophora paraënsis

Four new indolopyridoquinazoline alkaloids were isolated in small amount from the bark of Euxylophora paraänsis Hub. Chemical reactions and spectroscopic evidence indicated that euxylophorine-C has structure (Ia), which was confirmed by synthesis. The structures of the other alkaloids, euxylophorine-D (IIa), euxylophoricine-D (IIIa) and euxylophoricine-E (IVa), were determined through correlation with (Ia).     

Naturally-occurring tetrahydro-β-carboline alkaloids derived from tryptophan are oxidized to bioactive β-carboline alkaloids by heme peroxidases

β-Carbolines are indole alkaloids that occur in plants, foods, and endogenously in mammals and humans, and which exhibit potent biological, psychopharmacological and toxicological activities. They form from naturally-occurring tetrahydro-β-carboline alkaloids arising from tryptophan by still unknown way and mechanism. Results in this research show that heme peroxidases catalyzed the oxidation of tetrahydro-β-carbolines (i.e. 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid) into aromatic β-carbolines (i.e. norharman and harman, respectively). This oxidation followed a typical catalytic cycle of peroxidases through redox intermediates I, II, and ferric enzyme. Both, plant peroxidases (horseradish peroxidase, HRP) and mammalian peroxidases (myeloperoxidase, MPO and lactoperoxidase, LPO) catalyzed the oxidation in an efficient manner as determined by kinetic parameters (V_MAX and K_M). Oxidation of tetrahydro-β-carbolines was inhibited by peroxidase inhibitors such as sodium azide, ascorbic acid, hydroxylamine and excess of H₂O₂. The formation of aromatic β-carbolines by heme peroxidases can help to explain the presence and activity of these compounds in biological systems.     

Attract and deter: a dual role for pyrrolizidine alkaloids in plant–insect interactions

Pyrrolizidine alkaloids (PAs) are the major defense compounds of plants in the Senecio genus. Here I will review the effects of PAs in Senecio on the preference and performance of specialist and generalist insect herbivores. Specialist herbivores have evolved adaptation to PAs in their host plant. They can use the alkaloids as cue to find their host plant and often they sequester PAs for their own defense against predators. Generalists, on the other hand, can be deterred by PAs. PAs can also affect survival of generalist herbivores. Usually generalist insects avoid feeding on young Senecio leaves, which contain a high concentration of alkaloids. Structurally related PAs can differ in their effects on insect herbivores, some are more toxic than others. The differences in effects of PAs on specialist and generalists could lead to opposing selection on PAs, which may maintain the genetic diversity in PA concentration and composition in Senecio species.     

Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on D3 and σ2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and σ2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for σ2 receptors as well as σ2 versus σ1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and σ receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds.