Bisindole alkaloids from Voacanga grandifolia leaves.

Two new bisindole alkaloids, 12'-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia, together with two known bisindole alkaloids. Their structures were elucidated on the basis of 1D and 2D NMR data. 1 and 2 showed potent antimalarial activity against Plasmodium falciparum 3D7 and very low cytotoxic activity against a human cell line, HepG2 cells.

Sanjecumins A and B: new limonoids from Sandoricum koetjape.

Two new limonoids, sanjecumins A (1) and B (2), have been isolated from the leaves of Sandoricum koetjape, together with sandoripins A (3) and B (4). Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Sandoripins A (3) and B (4) moderately inhibited nitric oxide production in mouse macrophage-like cell line J774.1 stimulated by lipopolysaccharide.

Alstiphyllanines I-O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity.

Seven new ajmaline type alkaloids, alstiphyllanines I-O (1-7) were isolated from the leaves of Alstonia macrophylla together with six related alkaloids (8-13). Structures and stereochemistry of 1-7 were fully elucidated and characterized by 2D NMR analysis. A series of alstiphyllanines I-O (1-7) as well as the known ajmaline type alkaloids (8-13) showed that they relaxed phenylephrine (PE)-induced contractions against rat aortic ring. Among them, vincamedine (10) showed potent vasorelaxant activity, which may be mediated through inhibition of Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCs) and/or receptor-operated Ca(2+) channels (ROCs) as well as partially mediated the NO release from endothelial cells. The presence of substituents at both N-1 and C-17 may be important to show vasorelaxation activity.

Lecythomycin, a new macrolactone glycoside from the endophytic fungus Lecythophora sp.

A new macrolactone glycoside, lecythomycin (1), 23-methyl-3-(1-O-mannosyl)-oxacyclotetracosan-1-one, was isolated from the endophytic fungus Lecythophora sp. (code 30.1), an endopyte of the Indonesian plant Alyxia reinwardtii. The structure of 1 was elucidated on the basis of NMR spectroscopic and mass spectrometric data. The isolated compound displayed antifungal activity against strains of Aspergillus fumigatus and Candida kruzei at minimal inhibitory concentrations (MIC) of 62.5-125 microg/mL.

Melidianolic acid A and B, new antimalarial acyclic diterpenes from Aphanamixis grandifolia.

Two new acyclic diterpenes, melidianolic acids A (1) and B (2), have been isolated from the bark of Aphanamixis grandifolia. Their structures were elucidated on the basis of spectroscopic and chemical methods. Melidianolic acids A (1) and B (2) showed antimalarial activity against Plasmodium falciparum 3D7 with IC50 of 6.1 and 7.3 microg/mL, respectively.

Inhibitors of nitric oxide production from Stemona javanica.

In our screening program for bioactive natural products from our library of tropical plants, the extract prepared from the roots of Stemona javanica inhibited NO production in mouse macrophage-like cell line J774.1 stimulated by lipopolysaccharide (LPS). Bioassay-guided fractionation of the extract from S. javanica led to the isolation of two active compounds, stemofoline (1) and stemanthrene C (2). The inhibition mechanism of 1 was proposed to suppress iNOS expression in J774.1 cells stimulated by LPS, whereas that of 2 was due to potent radical scavenging activity resulting in NO inhibitory activity.

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.

Chemical constituents of the endophytic fungus Lecythophora sp. isolated from Alyxia reinwardtii.

Seven compounds, (2R)-3-(2-hydroxypropyl)-benzene-1,2-diol (1), kojic acid (2), 7-O-acetyl-kojic acid (3), p-hydroxybenzoic acid (4), emodine (5), 7-chloroemodine (6), and ergosterol-5,8-peroxide (7) were isolated from the endophytic fungus Lecythophora sp. (specimen codes 30.1 and 30.5), which were isolated from Alyxia reinwardtii (Apocynaceae).

Alasmontamine A, A first tetrakis monoterpene indole alkaloid from Tabernaemontana elegans.

A novel tetrakis monoterpene indole alkaloid, alasmontamine A (1) consisting of bis-vobtusine-type skeletons, was isolated from the leaves of Tabernaemontana elegans. The structure including the relative stereochemistry was elucidated on the basis of spectroscopic data. Alasmontamine A (1) exhibited moderate cell growth inhibitory activity against HL-60 cells.

Synthesis and structure-activity relationships of cassiarin A as potential antimalarials with vasorelaxant activity.

Cassiarin A 1, a tricyclic alkaloid, isolated from the leaves of Cassia siamea (Leguminosae), shows powerful antimalarial activity against Plasmodium falciparum in vitro as well as P. berghei in vivo, which may be valuable leads for novel antimalarials. Interactions of parasitized red blood cells (pRBCs) with endothelium in aorta are especially important in the processes contribute to the pathogenesis of severe malaria. Nitric oxide (NO) reduces endothelial expression of receptors/adhesion molecules used by pRBC to adhere to vascular endothelium, and reduces cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 showed vasorelaxation activity against rat aortic ring, which may be related with NO production. A series of a hydroxyl and a nitrogen-substituted derivatives and a dehydroxy derivative of 1 have been synthesized as having potent antimalarials against P. falciparum with vasodilator activity, which may reduce cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 exhibited a potent antimalarial activity and a high selectivity index in vitro, suggesting that the presence of a hydroxyl and a nitrogen atom without any substituents may be important to show antimalarial activity. Relative to cassiarin A, a methoxy derivative showed more potent vasorelaxant activity, although it did not show improvement for inhibition of P. falciparum in vitro. These cassiarin derivatives may be promising candidates as antimalarials with different mode of actions.

Cassiarins C-E, antiplasmodial alkaloids from the flowers of Cassia siamea.

Three new alkaloids, cassiarins C-E (1-3), and a new chromone, 10,11-dihydroanhydrobarakol (4), which showed moderate antiplasmodial activity against Plasmodium falciparum 3D7, were isolated from flowers of Cassia siamea, and the structures of 1-4 were elucidated by 2D NMR analysis and chemical transformation. Cassiarin D (2) was a dimeric compound consisting of 5-acetonyl-7-hydroxy-2-methylchromone and cassiarin C (1), and cassiarin E (3) was a dimer of cassiarins A and C (1).

Biscarpamontamines A and B, an aspidosperma-iboga bisindole alkaloid and an aspidosperma-aspidosperma bisindole alkaloid, from Tabernaemontana sphaerocarpa.

Two new bisindole alkaloids, biscarpamontamine A (1), possessing an aspidosperma-iboga-type skeleton, and biscarpamontamine B (2), having an aspidosperma-aspidosperma-type skeleton, were isolated from stems of Tabernaemontana sphaerocarpa, and their structures were elucidated on the basis of spectroscopic data analysis. The absolute configuration of biscarpamontamine B (2) was established by comparison of its CD spectrum and with that of vobtusine (3). Biscarpamontamine B (2) showed potent cytotoxicity against various human cancer cell lines.

Alstiphyllanines A-D, indole alkaloids from Alstonia macrophylla.

Four new alkaloids, alstiphyllanines A-D (1-4), were isolated from Alstonia macrophylla, and their structures were determined by MS and 2D NMR analyses. Alkaloids 1-4 showed moderate antiplasmodial activity against Plasmodium falciparum and vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

Ceramicines B-D, new antiplasmodial limonoids from Chisocheton ceramicus.

Three new limonoids, ceramicines B-D (1-3), have been isolated from the bark of Chisocheton ceramicus. Structures and stereochemistry of 1-3 were fully elucidated and characterized by 2D NMR analysis. Ceramicines exhibited a moderate antiplasmodial activity.

Alkaloids from the seeds of Peganum harmala showing antiplasmodial and vasorelaxant activities.

Bioassay-guided purification from the seeds of Peganum harmala led to the isolation of harmine (1), harmaline (2), vasicinone (3), and deoxyvasicinone (4). Harmine (1) and harmaline (2) showed a moderate in vitro antiplasmodial activity against Plasmodium falciparum. Quinazoline alkaloid, vasicinone (3), showed a vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

Sucutiniranes A and B, new cassane-type diterpenes from Bowdichia nitida.

Two new cassane-type diterpenes, sucutiniranes A (1) and B (2), have been isolated from the seeds of Bowdichia nitida together with 6alpha-acetoxyvouacapane (3) and 6alpha,7beta-diacetoxyvouacapane (4), and the structures of 1 and 2 were elucidated by using 2D NMR data and chemical correlations. Sucutinirane A (1) and 3 showed a moderate cytotoxicity against human colon carcinoma COLO201 cells, and 6alpha,7beta-diacetoxyvouacapane (4) showed in vitro antiplasmodial activity against parasite Plasmodium falciparum 3D7.

Chrobisiamone A, a new bischromone from Cassia siamea and a biomimetic transformation of 5-acetonyl-7-hydroxy-2-methylchromone into cassiarin A.

A new bischromone, chrobisiamone A (1) with an antiplasmodial activity has been isolated from the leaves of Cassia siamea and the structure was elucidated by 2D NMR analysis. Cyclization of 5-acetonyl-7-hydroxy-2-methylchromone (2) in the presence of ammonium acetate resulted in generation of cassiarin A (3) with an unprecedented tricyclic skeleton, supporting a biogenetic pathway proposed for 3.

Studies on the constituents from the fruits of Phaleria macrocarpa.

From the fruits of Phaleria macrocarpa, icariside C(3) (1), phalerin (2), and mangiferin (3) were isolated and their structures were identified on the basis of spectroscopic data. Icariside C(3) (1) showed a slow vasorelaxant activity against noradrenaline-induced contraction of isolated rat aorta. The structure of phalerin (2) was revised as 2,4',6-trihydroxy-4-methoxybenzophenone-2-O-beta-D-glucoside.

Cassiarins A and B, novel antiplasmodial alkaloids from Cassia siamea.

Two novel alkaloids with an unprecedented tricyclic skeleton, cassiarins A (1) and B (2), have been isolated from the leaves of Cassia siamea, and the structures were elucidated on the basis of spectroscopic data. Cassiarin A (1) showed a potent antiplasmodial activity.

Apoptosis inducing effect of andrographolide on TD-47 human breast cancer cell line.

Andrographolide isolated from Andrographis paniculata Ness (Acanthaceae) at 0.35 mM, 0.70 mM and 1.40 mM induced DNA fragmentation and increased the percentage of apoptotic cells when TD-47 human breast cancer cell line was treated for 24, 48 and 72 h. The results demonstrated that andrographolide can induce apoptosis in TD-47 human breast cancer cell line in a time and concentration-dependent manner by increase expression of p53, bax, caspase-3 and decrease expression of bcl-2 determined by immunohistochemical analysis.