Sesquiterpene alkaloids from Tripterygium hypoglaucum and Tripterygium wilfordii: a new class of potent anti-HIV agents

Five new sesquiterpene pyridine alkaloids [triptonines A (1) and B (2), and wilfordinines A (3), B (4), and C (5)] and two known compounds (peritassine A and hypoglaunine C) were isolated from Tripterygium hypoglaucum and a clinically used extract of Tripterygium wilfordii. The structures of 1-5 were elucidated by spectroscopic methods. The anti-HIV activity of 1, 2, and several related compounds was evaluated. Triptonine B (2) demonstrated potent anti-HIV activity with an EC(50) value of <0.10 microg/mL and an in vitro therapeutic index value of >1000.     

Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii

Nine new sesquiterpene pyridine alkaloids [wilfornines A (1), B (2), C (3), D (4), E (5), F (8), and G (9); wilfordinines I (6) and J (7)] and six known compounds (10-15) were isolated from a clinically used extract (T(II)) of Tripterygium wilfordii. The structures of 1-9 were elucidated by spectroscopic and chemical methods. The inhibitory effects on cytokine production of 1-3 and several related compounds were evaluated. Compounds 10 and 14 showed significant inhibitory effects on cytokine production.     

Antiprotozoal sesquiterpene pyridine alkaloids from Maytenus ilicifolia

As part of a bioprospecting program aimed at the discovery of antiprotozoal agents from the Brazilian flora, two new sesquiterpene pyridine alkaloids, ilicifoliunines A (1) and B (2), along with the known alkaloids aquifoliunine E-I (3) and mayteine (4), were isolated from the root bark of Maytenus ilicifolia. The structures of 1 and 2 were established on the basis of spectroscopic data interpretation. Alkaloid 3 displayed potent in vitro antiprotozoal activity against Leishmania chagasi and Trypanosoma cruzi, with IC(50) values of 1.4 and 41.9 μM, respectively, as well as low cytotoxicity against murine peritoneal macrophages (IC(50) of 1.8 mM).     

Phytochemical investigations of Stemona curtisii and synthetic studies on stemocurtisine alkaloids

The isolation of two new Stemona alkaloids, 1-hydroxyprotostemonine and stemocurtisine N-oxide, and a new benzofuran, stemofuran L, from the root extracts of Stemona curtisii is reported. The major known alkaloids from this plant extract, stemocurtisine, stemocurtisinol, and oxyprotostemonine, were also isolated along with oxystemokerrine N-oxide. The nonalkaloid components of this extract included a new benzofuran derivative, stemofuran L, the known stemofurans F, J, and K, dihydro-γ-tocopherol, and stigmasterol. Stemocurtisine and stemocurtisinol were converted to their respective N-oxides by oxidation. Stemocurtisine was converted to a tetracyclic derivative by oxidative cleavage of the γ-butyrolactone ring, while stemocurtisinol gave a novel lactam derivative by oxidative cleavage of the C-4 side chain under basic conditions. The acetylcholinesterase inhibitory activities of some known and new alkaloids and their derivatives are also reported. All were 10-20 times less active as acetylcholinesterase inhibitors than the pyrrolo[1,2-a]azepine Stemona alkaloids stemofoline and 1',2'-didehydrostemofoline. None of the stemofuran compounds showed significant antibacterial or antifungal activities.     

Oppositines A and B, sesquiterpene pyridine alkaloids from a Sri Lankan Pleurostylia opposita

Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been isolated from the plant Pleurostylia opposita, collected in Sri Lanka. The compounds were isolated and purified by solvent/solvent partitioning, column chromatography, and HPLC. Their structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1) and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values of 27 +/- 2 and 26 +/- 3 microM, respectively.     

Terpenoid indole alkaloids from Winchia calophylla

Three new indole alkaloids, N(4)-demethyl-12-methoxyalstogustine (1), 17-carboxyl-N(4)-methylechitamidine chloride (2), and 17-carboxyl-12-methoxy-N(4)-methylechitamidine chloride (3), along with 15 known alkaloids, were isolated from the ethanolic extract of the stem bark of Winchia calophylla. The structures of 1-3 were elucidated on the basis of spectroscopic means and chemical methods. The determination of relative configurations at C-19 and C-20 for 1-3 was aided by 13C NMR spectroscopic data. The absolute configurations of alkaloids 1-3 were determined by direct comparison of their CD spectra with those of known alkaloids. All the alkaloids were tested in cytotoxic assays against P-388 and A-549 tumor cell lines, and only two of them showed weak activity against the A-549 cell line.     

Antiplasmodial sesquiterpene alkaloids from the roots of Maytenus mekongensis

Eight new sesquiterpene alkaloids (1-8) and four known sesquiterpene alkaloids (9-12) have been isolated from the roots of Maytenus mekongensis. Structures were determined using extensive spectroscopic methods. The relative configuration of 7-epi-mekongensine (2) was established by single-crystal X-ray crystallographic analysis. The alkaloids were evaluated for antiplasmodial activity against Plasmodium falciparum, K1 strain, and for cytotoxicity using a panel of cell lines.     

Lepadins F-H, new cis-decahydroquinoline alkaloids from the Australian ascidian Aplidium tabascum

Chemical investigation of a Great Barrier Reef ascidian, Aplidium tabascum, has resulted in the isolation of three new cis-decahydroquinoline alkaloids, lepadins F-H (4-6). The three new compounds differ from the previously isolated lepadins A-C (1-3) in that they contain a fully saturated 5-hydroxyoctyl side chain attached at C-5, an unsaturated eight-carbon ester moiety attached to C-3, and opposite stereochemistry at C-5 and C-3. Lepadins G (5) and H (6) are epimers at C-2. NMR and molecular modeling studies indicated that the three new compounds adopt a chair-chair conformation in which the nitrogen equatorially substitutes the cyclohexyl ring. This contrasts with lepadins A-C (1-3), which adopt a chair-chair conformation in which the nitrogen axially substitutes the cyclohexyl ring.     

Insecticidal sesquiterpene pyridine alkaloids from Maytenus chiapensis

The new sesquiterpene pyridine alkaloids chiapenines ES-I (1), ES-II (2), ES-III (3), and ES-IV (4), in addition to the known alkaloids wilfordine (5), alatamine (6), wilforidine (7), alatusinine (8), euonine (9), euonymine (10), ebenifoline E-I (11), forrestine (12), mayteine (13), and 4-hydroxy-7-epi-chuchuhuanine E-V (14), were isolated from the leaves of Maytenus chiapensis. Their structures were elucidated by 1D and 2D NMR spectroscopy, including homonuclear and heteronuclear correlation (COSY, ROESY, HSQC, and HMBC) experiments. Wilfordine, alatusinine, and euonine exhibited strong antifeedant activity against Spodoptera littoralis.     

Dihydroagarofuran derivatives from the dried roots of Tripterygium wilfordii

Five new sesquiterpene derivatives, including dihydroagarofuran pyridine macrolides 1-4 and dihydroagarofuran ester 18, and 13 known dihydroagarofuran derivatives were isolated from the aqueous EtOH extract of the dried roots of Tripterygium wilfordii. An in vitro antiherpetic activity assay indicated that compounds 11 and 17 displayed weak and moderate inhibition against herpes simplex virus type II, respectively.     

Dihydroagarofuran sesquiterpene alkaloids from Maytenus putterlickoides

Two new dihydroagarofuran sesquiterpene alkaloids, putterines A (2) and B (3), and a known alkaloid, mayteine (1), were isolated from the root of Maytenus putterlickoides. The structures of these compounds were elucidated by various spectroscopic techniques, including 1H and 13C NMR, COSY, ROESY, HMBC, and high-resolution FABMS.     

Cytotoxic bisindole alkaloids from a marine sponge Spongosorites sp

Three new bisindole alkaloids of the hamacanthin class (1-3) and one new bisindole alkaloid of the topsentin class (6) were isolated along with known bisindole alkaloids (4, 5, 7-11) from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR, MS, and IR spectroscopic analyses. Configurations of compounds 1-4 were derived from 1H NMR data and optical rotation. Compounds 1, 4, 5, and 11 showed moderate to significant cytotoxicity against five human tumor cell lines, and compounds 1-5 showed weak antibacterial activity against clinically isolated methicillin-resistant strains.     

Pyridine alkaloids from Senna multijuga as acetylcholinesterase inhibitors

As part of an ongoing research project on Senna and Cassia species, five new pyridine alkaloids, namely, 12'-hydroxy-7'-multijuguinol (1), 12'-hydroxy-8'-multijuguinol (2), methyl multijuguinate (3), 7'-multijuguinol (4), and 8'-multijuguinol (5), were isolated from the leaves of Senna multijuga (syn. Cassiamultijuga). Their structures were elucidated on the basis of spectroscopic data analysis. Mass spectrometry was used for confirmation of the positions of the hydroxy groups in the side-chains of 1, 2, 4, and 5. All compounds exhibited weak in vitro acetylcholinesterase inhibitory activity as compared with the standard compound physostigmine.     

Dimeric aporphine alkaloids of Phoenicanthus obliqua from Sri Lanka.

A new dimeric aporphine alkaloid, phoenicanthusine (1), and six known alkaloids were isolated from the stem bark of Phoenicanthus obliqua. The structure of 1 was elucidated by 1D ((1)H, (13)C) and 2D ((1)H-(1)H COSY, HMQC, HMBC, and NOESY) NMR and HRMS studies. Phoenicanthusine represents the first example of a N-6--C-4' and C-7--C-5' linked dimeric aporphine alkaloid.     

Isolation and characterization of minor analogues of silvestrol and other constituents from a large-scale re-collection of Aglaia foveolata

Two new minor silvestrol analogues [2'-episilvestrol (1) and 2',5'-diepisilvestrol (2)], together with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds, were isolated from a large-scale re-collection of the CHCl(3)-soluble extract of the stem bark of Aglaia foveolata obtained in Kalimantan, Indonesia. The structures of the new compounds were established by interpretation of their spectroscopic data. All of the isolates were tested for cytotoxicity against HT-29 cells. The new silvestrol analogues, 1 and 2, were considerably less active as cytotoxic agents than silvestrol (7) and episilvestrol (5'-episilvestrol) (8) against this cell line, showing the importance of the configuration at C-2' in mediating such activity within this compound class. Several of the compounds isolated were also evaluated in a NF-κB (p65) inhibition assay.     

New alkaloids from Annona purpurea

Three new alkaloids, promucosine (1), romucosine F (2), and romucosine G (3), along with 28 known compounds, were isolated from the MeOH extract of stems of Annona purpurea. The structures of 1-3 were determined on the basis of spectral data and chemical evidence.     

Five new alkaloids from the leaves of Remijia peruviana

Three new indolylquinuclidine-type alkaloids, remijinine (1), epiremijinine (2), and 5-acetyl-apocinchonamine (3), and two new cinchonine-derived alkaloids, N-acetyl-deoxycinchonicinol (4) and N-acetyl-cinchonicinol (5), as well as the known alkaloids quinamine, conquinamine, cinchonine, and quinidine were isolated from the leaves of Remijia peruviana. The structures of the new alkaloids were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HMQC, and HMBC). The relative configuration at C-7 for remijinine (1) and, in consequence, for epiremijinine (2) was established by X-ray crystal structure analysis of the former.     

New quinoline alkaloids from Ruta chalepensis

The roots of Ruta chalepensis, collected from the northern Saudi desert, yielded two new quinoline alkaloids, namely, 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl?-hydroquinolin-4-one (1) and 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl?-4-methoxy-quinoline (2). Nine previously reported alkaloids, dictamnine, pteleine, skimmianine, rutacridone, isogravacridonechlorine, maculosidine, graveoline, graveolinine, and 4-methoxy-1-methyl-2(1H)-quinolinone, and coumarins, chalepensin, and umbelliferone were also isolated. Structure elucidations were based primarily on 1D and 2D NMR analyses and chemical transformations. Antimicrobial activity of these compounds is discussed.     

Ancistrotanzanine C and related 5,1'- and 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis

Three new naphthylisoquinoline alkaloids, the 7,3'-coupled ancistrotanzanine C (6), the 5,1'-coupled O-methylancistrocladinine (7), and the likewise 5,1'-coupled O,N-dimethylancistrocladine (8, previously known only as a partial-synthetic compound), have been isolated from the highland liana Ancistrocladus tanzaniensis, along with the two known 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (4) and ancistrotectorine (5). All of the compounds are S-configured at C-3 and bear an oxygen at C-6, and thus belong to the so-called Ancistrocladaceae type, similar to 1-3 previously isolated from this newly discovered plant species. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. The biological activities of the alkaloids against the pathogens causing malaria tropica, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated.     

Paratunamides A-D, oxindole alkaloids from Cinnamodendron axillare

Four new oxindole alkaloids, paratunamides A-D (1-4), containing a secologanin unit, were isolated from the bark of Cinnamodendron axillare, and their structures and relative configurations were elucidated by spectroscopic data. The absolute configuration at C-7 in 1-4 was assigned as S, S, R, and S, respectively, on the basis of the CD spectra.