Cytotoxic constituents from the higher plants Spathelia sorbifolia, Psorospermum febrifugum and the mosses Claopodium crispifolium, Anomodon attenuatus

Khanit Suwanborirux, Purdue University

Abstract

Fractionation of the 10% aqueous methanol extract of the twigs and leaves of Spathelia sorbifolia (Rutaceae) was directed by cytotoxicity against 9 PS cells in culture. On the basis of repetitive chromatography and analysis of spectroscopic data, the isolation and identification of eight chromones was achieved. These include three new chromones; 8-(2$\sp\prime$,3$\sp\prime$-dihydroxy-3$\sp\prime$-methylbutanyl) spatheliachromen 33, 8-(1$\sp\prime$,2$\sp\prime$,3$\sp\prime$-trihydroxy-3$\sp\prime$methylbutanyl)spatheliachromen 35, and 8-(3$\sp\prime$-hydroxy-3$\sp\prime$-methyl-trans-but-1$\sp\prime$-enyl)-O-methylisospatheliachromen 38 and five known chromones; 5-O-methylsorbifolin, 5-O-methylcneorumchromone K, spatheliabischromen, 7-O-methylisospatheliachromen, and 5-O-methylalloptaeroxylin. Spatheliabischromen and 5-O-methylsorbifolin showed cytotoxicity against the 9 PS, A-459, MCF-7, and HT-29 systems, and the chromone 35 is cytotoxic against the 9 PS system. Two novel xanthone analogs containing a new fused tetrahydrofurobenzofuran ring system, named febrifugin 26 and 5$\sp\prime$-hydroxyisofebrifugin 27, were isolated from the chloroform extract of Psorospermum febrifugum (Guttiferae). In addition, two new members of the psorospermin group, 4$\sp\prime$-O-acetyl-3$\sp\prime$,4$\sp\prime$-deoxypsorospermin-3$\sp\prime$,4$\sp\prime$-diol 28 and 3$\sp\prime$,4$\sp\prime$-deoxypsorospermin-3$\sp\prime$,4$\sp\prime$,5$\sp\prime$-triol 29, and a known xanthone, 1,3,5,6-tetrahydroxyxanthone 30 were isolated from the chloroform/isopropanol extract. Their structures were elucidated by extensive analysis of spectroscopic data and chemical correlations. Compound 28 showed significant cytotoxicity against the HT-29 system while compounds 26, 29, and 30 exhibited borderline activity. Two members of the moss family Thuidiaceae, Claopodium crispifolium and Anomodon attenuatus showed significant antitumor activity and were selected for fractionation. Fractionation of the active 10% aqueous methanol extracts guided by cytotoxicity against 9 PS and HT-29 cells in culture led to the isolation of ansamitocin P-3 in very low concentration (1 $\times$ 10$\sp{-5}$% from C. crispifolium and 4 $\times$ 10$\sp{-6}$% from A. attenuatus). Structural identity of the compound was determined by spectroscopic analysis and comparison with the authentic sample. Ansamitocin P-3 showed potent activity against A-549, HT-29, and MCF-7 cells in culture. The possibility of a relationship between the maytansinoid producing actinomycetes and the mosses, or a result of alleophathic response is suggested.

Degree

Ph.D.

Advisors

Chang, Purdue University.

Subject Area

Pharmacology

COinS