Wiwied Ekasari

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.

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.

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).

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.

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.

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.

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.

Antiplasmodial indole alkaloids from Leuconotis griffithii

A new indole alkaloid, leucoridine A N-oxide (1), consisting of two units of a strychnan type of skeleton, was isolated from the leaves of Leuconotis griffithii. Its structure was elucidated by various spectroscopic means such as NMR and MS, and also by chemical means. Antiplasmodial activity against Plasmodium falciparum 3D7 of indole alkaloids isolated from L. griffithii was investigated.

Antimalarial activity of cassiarin A from the leaves of Cassia siamea

The extracts and cassiarin A from the leaves of Cassia siamea showed promising antimalarial activities. The ethanol and chloroform extracts, alkaloid fraction, cassiarin A, and chloroquine as a positive control exhibited the inhibition against Plasmodium falciparum (IC 50 : 7.06, 2.41, 0.24, 0.005, and 0.006 μg/mL, respectively). The in vivo antimalarial activity was assessed using the 4-day suppressive test procedure. The ethanol, chloroform extracts, and alkaloid fraction were found to give an ED 50 34.7, 19.59, and 0.47 mg/kg, respectively (p.o.). The ED 50 values of cassiarin A and chloroquine were 0.17 and 0.21 mg/kg, respectively (i.p.). The result showed that cassiarin A deserved further investigation toward development of a promising antimalarial drug.

Indole alkaloids from the leaves of Alstonia scholaris

A new indole alkaloid, akuammidine-N-oxide (1) was isolated from the leaves of Alstonia scholaris (Apocynaceae) together with akuammidine (2), and the structure was elucidated by NMR spectral analysis and chemical correlation. Akuammidine (2) showed a moderate antiplasmodial activity.