Lee Kuo-Hsiung

Structure-antimicrobial activity relationships among the sesquiterpene lactones and related compounds

Abstract Thirty-six sesquiterpene lactones and related compounds were evaluated for antimicrobial activity against six strains of bacteria. The results obtained show that the beta unsubstituted cyclopentenone ring moiety contributes to moderate antimicrobial activity against Gram positive bacteria. The corresponding saturated compounds gave a more than ten-fold decrease in activity. The significant antimicrobial activity appears to be independent of the presence or absence of an α-methylene-γ-lactone moiety. A more than ten-fold diminution in antimicrobial activity was also observed when the beta position of the cyclopentenone ring was substituted. A similar result was found when the beta unsubstituted enone system was present in a six-membered ring. Enhanced activity was obtained by esterification of the hydroxyl group of helenalin as well as epoxidation of mexicanin-A.

Cytotoxic aporphines from artabotrys uncinatus and the structure and stereochemistry of artacinatine

Abstract The stem and stem bark of Artabotrys uncinatus afforded two cytotoxic aporphine alkaloids, liriodenine and atherospermidine, as well as a novel 11 -oxoaporphine, artacinatine, which is inactive. The structure of artacinatine was elucidated from spectral data in conjunction with a single-crystal X-ray analysis.

Sesquiterpene pyridine alkaloids from Maytenus emarginata: emarginatine-C and -D and cytotoxic emarginatine-E and emarginatinine

Abstract Four new sesquiterpene alkaloids, emarginatine-C, emarginatine-D, emarginatine-E and emarginatinine, were isolated from Maytenus emarginata . Emarginatine-E and emarginatinine showed cytotoxicity against human KB cells (ED 50 = 2.5 and 2.1 μg ml −1 , respectively). The structural determinations and activity relationships of these new compounds, and of emarginatine-A and emarginatine-B are discussed.

Structure and stereochemistry of pseudolarolide-H, a novel peroxy triterpene dilactone from Pseudolarix kaempferi

Pseudolarolide J (1), a novel nortriterpene lactone, has been isolated from the seeds of Pseudolarix kaempferi and structurally characterized from spectral data and X-ray crystallographic analysis.

Cytotoxic components of Diospyros morrisiana

Abstract Two cytotoxic compounds, isodiospyrin and β-amyrin, in addition to an inactive triterpene, olean-12-en-3-one, have been isolated from Diospyros morrisiana. The cytotoxic activity of isodiospyrin, which has ed 50 values of 4.9 and 0.59 μg/ml, respectively, against HCT-8 colon tumour and P-388 lymphocytic leukemia, was demonstrated for the first time. Results of single-crystal X-ray analyses of β-amyrin acetate and olean-12-en-3-one are also reported.

In vivo and in vitro effects of helenalin on mouse hepatic microsomal cytochrome P450

Helenalin, a natural plant product with significant antitumor activities, decreased male BDF1 mouse hepatic microsomal cytochrome P450 contents in vivo and in vitro. A single i.p. dose of 25 mg helenalin/kg body weight significantly (P less than 0.05) decreased microsomal cytochrome P450 contents and inhibited cytochrome P450-dependent mixed-function oxidase activities within 1-2 hr post-exposure. Helenalin (1.0 mM) decreased microsomal cytochrome P450 contents in vitro by 11% in the absence of NADPH and by 32% in the presence of NADPH. These in vitro and in vivo decreases in cytochrome P450 were accompanied by comparable decreases in total microsomal heme contents. Helenalin (1.0 mM) increased mouse hepatic microsomal oxygen consumption and NADPH utilization by 3.2 and 5.4 nmol/min/mg protein respectively. Helenalin (1.0 mM) significantly (P less than 0.05) increased microsomal lipid peroxidation in vitro, and this helenalin-induced increase in lipid peroxidation was inhibited completely by the addition of 0.05 mM EDTA. However, microsomal cytochrome P450 contents were equally affected by helenalin in the presence or absence of EDTA, suggesting that lipid peroxidation did not contribute to the helenalin-induced decrease in cytochrome P450. The addition of 0.05 mM hemin to microsomes treated in vitro with 1.0 mM helenalin resulted in a 58% recovery of cytochrome P450 contents. This ability of hemin to reconstitute cytochrome P450 in helenalin-treated microsomes suggests that helenalin produced a selective loss of heme from the cytochrome P450 holoprotein, and that the resulting cytochrome P450 apoprotein remained intact after helenalin treatment. The increased loss of microsomal cytochrome P450 produced by helenalin in the presence of NADPH suggests that a helenalin metabolite may be responsible for heme loss and the in vitro destruction of cytochrome P450.