[Studies on chemical constituents of Fragaria ananassa Duch].

OBJECTIVE: To study the chemical constituents from the fruit of Fragaria ananassa. METHOD: Using chromatographic methods to isolate compounds and chemical and spectral methods to elucidate their structures. RESULT: Three compounds, 9, 19-cyclolanost-24-en-3-ol(1), 14-methyl-stigmasta-7, 24(28)-dien-3-ol(2) and beta-sitosterol(3) were isolated from the freeze-dried powder. CONCLUSION: All of the compounds were obtained from this plant for the first time.

Topoisomerase II inhibition by aporphine alkaloids.

The aporphine alkaloids (+)-dicentrine and (+)-bulbocapnine are non-planar molecules lacking features normally associated with DNA binding by intercalation or minor groove binding. Surprisingly, dicentrine showed significant activity as a topoisomerase II (EC 5.99.1.3) inhibitor and also was active in a DNA unwinding assay. The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II. Bulbocapnine, which differs from dicentrine only by the presence of a hydroxyl group at position 11 and the absence of a methoxyl group at position 9, was inactive in all assays. Molecular modeling showed that dicentrine can attain a relatively planar conformation, whereas bulbocapnine cannot, due to steric interaction between the 11-hydroxyl group and an oxygen of the methylenedioxy ring. These observations suggest that dicentrine is an "adaptive" DNA intercalator, which can bind DNA only by adopting a somewhat strained planar conformation. The requirement of a suboptimal conformation to achieve DNA binding appears to make dicentrine a weaker topoisomerase II inhibitor than the very planar oxoaporphine alkaloid liriodenine. These results suggest that it may be possible to modulate DNA binding and biologic activity of drugs by modifications affecting their ability to adopt planar conformations.

DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia.

An ethanol extract of Psoralea corylifolia caused strong DNA polymerase inhibition in a whole cell bioassay specific for inhibitors of DNA replication enzymes. Bioassay-directed purification of the active compounds led to the isolation of the new compound corylifolin (1) and the known compound bakuchiol (2) as DNA polymerase inhibitors. On the basis of the structures of 1 and 2, resveratrol (3) was tested and found to be active as a DNA polymerase inhibitor in this bioassay. Neobavaisoflavone (4) was isolated as a DNA polymerase inhibitor, daidzein (5) as a DNA polymerase and topoisomerase II inhibitor, and bakuchicin (6) as a topoisomerase II inhibitor.

Inhibition of topoisomerase II by liriodenine.

The cytotoxic oxoaporphine alkaloid liriodenine, isolated from Cananga odorata, was found to be a potent inhibitor of topoisomerase II (EC 5.99.1.3) both in vivo and in vitro. Liriodenine treatment of SV40 (simian virus 40)-infected CV-1 cells caused highly catenated SV40 daughter chromosomes, a signature of topoisomerase II inhibition. Strong catalytic inhibition of topoisomerase II by liriodenine was confirmed by in vitro assays with purified human topoisomerase II and kinetoplast DNA. Liriodenine also caused low-level protein-DNA cross-links to pulse-labeled SV40 chromosomes in vivo, suggesting that it may be a weak topoisomerase II poison. This was supported by the finding that liriodenine caused topoisomerase II-DNA cross-links in an in vitro assay for topoisomerase II poisons. Verapamil did not increase either liriodenine-induced protein-DNA cross-links or catalytic inhibition of topoisomerase II in SV40-infected cells. This indicates that liriodenine is not a substrate for the verapamil-sensitive drug efflux pump in CV-1 cells.

Anti-AIDS agents, 9. Suberosol, a new C31 lanostane-type triterpene and anti-HIV principle from Polyalthia suberosa.

A new C31 lanostane-type triterpene, assigned the trivial name suberosol [1], has been isolated from Polyalthia suberosa as an anti-HIV principle. The structure has been characterized as 24-methylenelanost-7,9(11)-diene-3 beta, 15 alpha-diol (suberosol) [1], based on spectroscopic evidence. Compound 1 was found to show anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 3 micrograms/ml.

[Studies on the chemical constituents of Annona squamosa].

Twelve compounds were isolated from Annona squamosa. Their structures were identified as liriodenine (AS-1), moupinamide (AS-2), -(-)-kauran-16 alpha-ol-19-oic acid (AS-3), 16 beta, 17-dihydroxy-(-)-kauran-19-oic acid (AS-4), anonaine (AS-5), 16 alpha, 17-dihydroxy-(-)-kauran-19-oic acid (AS-6), (-)-isokaur-15(16)-en-17,19-dioic acid (AS-7), squamosamide (AS-8), 16 alpha-methoxy-(-)-kauran-19-oic acid (AS-9), sachanoic acid (AS-10), (-)-kauran-19-al-17-oic acid (AS-11), daucosterol (AS-12). Among them, AS-8 is a new amide, AS-9 is a new natural product.

New cytotoxic aristolactams from Pararistolochia flos-avis.

Two new aristolactams, aristolactam-FI [1] and -FII [2], were isolated from active extracts of Pararistolochia flos-avis. Their structures were elucidated on the basis of nmr, ms, uv, and ir spectral data. Aristolactam-I [3] and -AII [4] were also isolated from this plant. Aristolactam-AII showed cytotoxicity against PS and KB cells in culture.