Activity of Extracts and Alkaloids of Thai Alstonia Species Against Human Lung Cancer Cell Lines

Abstract

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 macraistonine. 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 µM, but was about 10³ times less potent than vinblastine sulphate. The monomeric alkaloid, talcarpine, was found to be inactive. Pleiocarpamine, O-methylmacralstonine and macraistonine were all considerably less active than villalstonine.

key words

Alstonia - Apocynaceae - indole alkaloids - O-methylmacralstonine - villalstonine - lung cancer cell lines - cytotoxicity