Bioactive constituents of Pogonopus speciosus (Rubiaceae), Persea major (Lauraceae), and Endlicheria dysodantha (Lauraceae)

Wen-wen Ma, Purdue University

Abstract

Using brine shrimp lethality directed fractionation, the EtOH extract of the roots of Endlicheria dysodantha (Lauraceae) yielded eight neolignans and four benzylbezoates. Five of the neolignans are new compounds including dysodanthins A, B, and D-F. Dysodanthin A, B, and E showed mild activities against human tumor cells (ED$\sb{50}$ 2.76 to 9.86 $\mu$g/ml). Megaphone acetate, one of the known neolignans, was isolated in relatively large amount (yield: $\sim$0.3%) (LC$\sb{50}$ for BS: 253 ppm) and showed significant activity to human tumor cell lines (ED$\sb{50}$ for A-549: 4.35 $\times$ 10$\sp{-2}$; MCF-7: 2.16; HT-29: 6.08 $\times$ 10$\sp{-2}$ $\mu$g/ml). Another known neolignan, megaphyllone acetate, also showed considerably activity against human tumor cells (ED$\sb{50}$ for A-549: 2.26 $\times$ 10$\sp{-1}$, MCF-7: 4.02 $\times$ 10$\sp{-1}$, HT-29: 4.10 $\times$ 10$\sp{-2}$ $\mu$g/ml). This is the first report that these neolignans have been isolated from the genus Endlicheria. Four known benzylbenzoates showed significant brine shrimp activity: benzyl 2-hydroxybenzoate (LC$\sb{50}$ 0.34 ppm), benzyl 2-hydroxyl-6-methoxybenzoate (LC$\sb{50}$ 3.60 ppm), benzyl 2,6-dimethoxybenzoate (LC$\sb{50}$ 1.83 ppm), and benzyl 2,5-dimethoxy benzoate (LC$\sb{50}$ 1.45 ppm). However, they displayed only weak inhibition to the human tumor cells (ED$\sb{50}$ 27 to $>$100 $\mu$g/ml) and crown gall tumors on potato discs (inhibition %: 6.3-38). Although benzylbenzoates are widespread in the Lauraceae, this is the first report of these compounds being isolated from Endlicheria. The structures of these neolignans and benzylbenzoates were determined by spectroscopic analysis. Fractionation of the EtOH extract of the bark of Persea major (Lauraceae), with the direction of brine shrimp lethality, led to the isolation of three novel $\delta$-lactones: majorynolide (LC$\sb{50}$ 0.89 ppm), majorenolide (LC$\sb{50}$ 0.36 ppm), and majoranolide (LC$\sb{50}$ 63 ppm). These $\delta$-lactones showed mild activity to the human tumor cell lines (ED$\sb{50}$ 1.7-13.8 $\mu$g/ml) and remarkable inhibition to the crown gall tumors on the potato discs (Inhibition %: 46, 86, 84, respectively). Their structures were elucidated by extensive analysis of chemical and spectroscopic data. These exocyclic $\alpha$,$\beta$-unsaturated-4-hydroxy-$\delta$-lactones represent an interesting new class of bioactive natural heterocycles. Using the simple brine shrimp lethality assay to direct the fractionation of the sap extract of Pogonopus speciosus (Rubiaceae), two alkaloids, tubulosine and psychotrine, were isolated. Tubulosine showed significant activities in brine shrimp lethality assay (LC$\sb{50}$ 0.02 ppm), in the inhibition of the growth of crown gall tumors on the potato discs (Inhibition %: 84), and in human tumor cell cytotoxicities test (ED$\sb{50}$ for A-549: 5.4 $\times$ 10$\sp{-9}$; MCF-7: 1 $\times$ 10$\sp{-5}$; HT-29: 1.6 $\times$ 10$\sp{-7}$ $\mu$g/ml). This is the first report of these two alkaloids being isolated from Pogonopus. The structures of these two alkaloids were identified with spectroscopic methods. Molecular modeling demonstrated some interesting features required for the biological activities of this type of alkaloid.

Degree

Ph.D.

Advisors

McLaughlin, Purdue University.

Subject Area

Biomedical research|Pharmaceuticals|Analytical chemistry

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