Isolation and structure elucidation of cytotoxic agents from the higher plant Psorospermum febrifugum

Mohamed Ibrahim Abou-shoer, Purdue University

Abstract

Activity-directed fractionation of the ethanolic extract of Psorospermum febrifugum has led to a number of significantly active fractions devoid of psorospermin. Chemical study of these fractions has led to the isolation of a series of novel active xanthone analogs of the parent compound. Repetitive fractionation and chromatography, guided by in vitro 9PS cytotoxic activity and in vitro 3PS antitumor activity, has led to the isolation of twelve novel xanthones. Six compounds exhibited significant cytotoxic activity while two other compounds showed borderline cytotoxic activity against PS cells in culture. One compound was found to exhibit both significant cytotoxic and antitumor activity. Analysis using UV, IR, MS, PMR and CMR spectroscopy allowed the structural elucidation of these twelve compounds which were found to belong to two groups of xanthonoids. Eight of the isolated compounds were found to be of the furanoxanthone type while the other four belong to the rare xanthonolignoid class. The difference in structure among the furanoxanthones is in either the substitution pattern on the C-1 and C-5 carbons of the xanthone nucleus or at the C-4$\sp\prime$ and C-5$\sp\prime$ carbons of the side chain part of the molecule. 5$\sp\prime$Hydroxypsorospermin was isolated from one of the fractions that exhibited in vivo antitumor activity. This compound was found to have both in vitro cytotoxic and in vivo antitumor activity (9PS, 7 $\times$ 10$\sp{\rm -5}$ g/ml; 3PS, 136/16 (T/C %/dose mg/kg)). Compounds 4$\sp\prime$-ethoxy-3$\sp\prime$, 4$\sp\prime$-deoxypsorospermin-3$\sp\prime$-ol, 4$\sp\prime$-chloro-5-0-methyl-3$\sp\prime$, 4$\sp\prime$deoxypsorospermin-3$\sp\prime$, 5$\sp\prime$-diol, 4$\sp\prime$-methoxy-3$\sp\prime$, 4$\sp\prime$-deoxypsorospermin-3$\sp\prime$-ol and 3$\sp\prime$, 4$\sp\prime$-deoxypsorospermin-3$\sp\prime$, 4$\sp\prime$, 5$\sp\prime$-triol were found to exhibit significant activity against PS cells in culture with an ED$\sb{\rm 50}$ of 2 $\times$ 10$\sp{\rm -4}$, $<<10\sp{-5}$, 1 $\times$ 10$\sp{\rm -2}$, 2 $\times$ 10$\sp{\rm -4}$ and 3 $\times$ 10$\sp\circ$ g/ml respectively. Isocadensin D, isocadensin D monoacetate, 6-hydroxy-8-methoxycadensin D and 8-methoxycadensin D were isolated as new members of the xanthonolignoid class. Aged alkaloidal extracts of Cephalotaxus harringtonia were analyzed by mass spectrometry. Cephalotaxinamide was isolated as the main component of the neutral fraction of the alkaloidal residue. Cephalotaxine and desmethylcephalotaxinone were isolated as the major components of the alkaloidal mixture obtained by fractionation of the aged alcoholic extracts of C. harringtonia roots.

Degree

Ph.D.

Advisors

Chang, Purdue University.

Subject Area

Pharmaceuticals|Pharmacology

COinS