Cytotoxic activity of acetogenins and styryl lactones isolated from Goniothalamus undulatus Ridl. root extracts against a lung cancer cell line (COR-L23).

An investigation of the chemical constituents in a dichloromethnae extract of Goniothalamus undulatus root led to the isolation of three known styryl lactones (5-acetoxyisogoniothalamin oxide, O-acetylaltholactone and altholactone), and four known annonaceous acetogenins (annonacin, cis-annonacin, goniothalamicin and cis-goniothalamicin). These compounds were subjected to a sulphorhodamine B (SRB) cytotoxicity assay against human large cell lung carcinoma (COR-L23), and normal human fetal fibroblast (MRC-5), cell lines. The isolated acetogenins showed higher cytotoxic activity against COR-L23 compared to the styryl lactones, with IC50 values in the range of 0.5-1.7 µM and 7.4-15.4 µM, respectively. A similar pattern of cytotoxicity was also observed against the other cell line (MRC-5); acetogenins IC50 values were in the range of 11.8-31.4 µM, and those for styryl lactones were in the range of 48.7-102.8 µM. This is the first report of a bioassay-guided isolation of chemical constituents from G. undulatus and on cytotoxic studies of the isolated compounds using these particular lung cancer cell lines.

Cytotoxic activity of indole alkaloids from Alstonia macrophylla.

Thirteen indole alkaloids isolated from the root bark of Alstonia macrophylla and a semisynthetic bisindole O-acetylmacralstonine have been assessed for cytotoxic activity against two human lung cancer cell lines, MOR-P (adenocarcinoma) and COR-L23 (large cell carcinoma), using the SRB assay. Pronounced cytotoxic activity was exhibited by the bisindoles on both cell lines. This suggests that, in comparison with the corresponding monomeric indoles, at least part of both the ring systems present in the bisindoles is essential for cytotoxic activity. The potent alkaloids were further tested against a human normal cell line (breast fibroblasts) and other human cancer cell lines including StMI1 1a (melanoma), Caki-2 (renal cell carcinoma), MCF7 (breast adenocarcinoma), and LS174T (colon adenocarcinoma). The bisindoles O-acetylmacralstonine, villalstonine and macrocarpamine were found to possess pronounced activity against cancer cell lines with IC50 values in the range of 2-10 microM, with no discernible cell-type selectivity. However, O-acetylmacralstonine displayed discernibly less toxicity against the normal breast fibroblasts.

Antiplasmodial activity of extracts and alkaloids of three Alstonia species from Thailand.

Methanol extracts prepared from various parts of Alstonia scholaris, A. macrophylla and A. glaucescens, collected from Thailand, have been assessed for antiplasmodial activity against multidrug-resistant K1 strain of Plasmodium falciparum cultured in human erythrocytes. Pronounced antiplasmodial activity was exhibited by methanol extract of the root bark of A. macrophylla with an IC50 value of 5.7 micrograms/ml. Thirteen indole alkaloids were isolated from the active extract. These alkaloids and a semisynthetic bisindole O-acetylmacralstonine were subsequently tested against the K1 strain of P. falciparum. Pronounced antiplasmodial activity was observed mainly among the bisindole alkaloids, particularly villalstonine and macrocarpamine with IC50 values of 0.27 and 0.36 microM, respectively. The potent alkaloids were further tested against T9-96, the chloroquine-sensitive strain of P. falciparum. It has been found that the active alkaloids, in contrast to chloroquine, have significantly higher affinity to the K1 strain than to the T9-96 strain.

Activity of extracts and alkaloids of thai Alstonia species against human lung cancer cell lines.

Methanol extracts of root barks of Alstonia macrophylla, A. glaucescens, and A. scholaris, collected from Thailand, have been assessed for cytotoxic activity against two human lung cancer cell lines, MOR-P (adenocarcinoma) and COR-L23 (large cell carcinoma), using the SRB assay. Significant cytotoxic activity was exhibited by the extract of A. macrophylla on both cell lines. Activity-directed fractionation led to the isolation of a novel indole alkaloid, O-methylmacralstonine, from the most active fraction of A. macrophylla along with four known alkaloids, talcarpine, villalstonine, pleiocarpamine, and macralstonine. Structure elucidation of the novel alkaloid was based on spectroscopic methods, especially 2D-NMR. The bisindole villalstonine was found to possess pronounced activity on both cell lines with an IC50 value less than 5 muM, but was about 10(3) times less potent than vinblastine sulphate. The monomeric alkaloid, talcarpine, was found to be inactive. Pleiocarpamine, O-methylmacralstonine and macralstonine were all considerably less active than villalstonine.