Phebalosin from the Bark of Micromelum minutum

Journal of Natural Products
1986.0

Abstract

In Thailand, the shrub Micromelum minuturn (Forst. f.) Seem (syn. M. pubescens Blume) (Rutaceae) (1) is named "Mui-chang" or "Hat-sa-khum," and the stems, fruits, flowers, leaves, and roots are employed medicinally for a variety of indications (2). Previous phytochemical studies have yielded several prenylated coumarins (3-8) and a pyranoquinoline alkaloid (7). Of the coumarins tested biologically, microminutin is weakly cytotoxic (7), and micromelin has antitumor activities (9). From the stem bark, we have now isolated phebalosin, a known prenylated coumarin (10- 12) new to this species, along with a trace ofmicromelin (3,4). The ¹³C-nmr spectrum ofphebalosin, which has not been previously reported (7,9), along with ¹H nmr, high resolution ms, eims, uv, ir, mp, and co-tlc were usehl in identifying the isolated compounds (10- 14). The co-occurrence of the epoxide (phebalosin) with the related carbonyl compound (micropubescin) may be of biogenetic interest (15).Phebalosin was significantly toxic to brine shrimp (16) (LC₅₀ 47 ppm, 95% confidence interval 31-69 ppm) and significantly inhibitory to thedevelopment ofcrown gall tumors on potatodiscs (17)(-64% and -70% in two independent determinations). However, insignificant cytotoxic activity (18) was observed (9KB ED₅₀>20 µg/ml; 9PS ED₅₀ 27 µg/ml), and no activity was observed in the 9ASK astrocytoma reversal assay (19). In the 3PS (P-388) in vivo murine leukemia system (18), phebalosin was inactive in doses up to 25 mg/kg, but insufficient material was available for testing at higher doses.

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