David K. Ho

Effects of synthetic and naturally occurring flavonoids on benzo[a]pyrene metabolism by hepatic microsomes prepared from rats treated with cytochrome P-450 inducers

Activity-directed fractionation of Trifolium pratense resulted in isolation of the isoflavone biochanin A, a potent inhibitor of metabolic activation of the carcinogen benzo[a]pyrene (B[a]P) in cells in culture. To determine the structural features required for maximal inhibition of cytochrome P-450 mediated metabolism of B[a]P, the inhibitory potencies of 23 flavonoids on metabolism of B[a]P to water-soluble derivatives were examined in liver S-9 homogenate from rats induced with Aroclor 1254. Flavones were much more efficient inhibitors than their corresponding isoflavone or flavanone analogs. Most flavonols were as effective inhibitors as their flavone analogs with the exception of kaempferide. Flavones with two hydroxyl or two methoxyl groups at positions 5 and 7 were the most active. Although all eight flavonoids tested effectively inhibited B[a]P metabolism by beta-naphthoflavone-induced microsomes, none were very effective inhibitors of B[a]P metabolism by phenobarbitol-induced microsomes, and only three were effective inhibitors of B[a]P metabolism by microsomes from non-induced rats. These results indicate that flavones or flavonols that contain free 5- and 7-hydroxyls are potent inhibitors of P-450 induced by beta-naphthoflavone (P-450IA1 and/or P-450IA2) and may potentially be useful as chemopreventive agents against hydrocarbon-induced carcinogenesis.

Stereochemical studies of the C-methylation of deoxycytidine catalyzed by Hha I methylase and the N-methylation of deoxyadenosine catalyzed by EcoRI methylase

The steric course of methyl group transfer catalyzed by two DNA methylases, HhaI methylase, a DNA (cytosine-5)-methyltransferase, and EcoRI methylase, which methylates at N6 of adenosine, has been studied with (methyl-R)- and (methyl-S)-[methyl-2H1,3H]adenosylmethionine as the methyl donor, using as substrates poly-d(GC) (HhaI) and the dodecamer oligonucleotide duplex d(CGCGAATTCGCG) (EcoRI), respectively. The methylated nucleotides were degraded to convert the chiral methyl groups into acetic acid for configurational analysis. It was found that both enzymatic reactions proceed with inversion of configuration of the methyl group.

Stereochemistry of mono-tetrahydrofuranyl moiety in cytotoxic polyketides. Part B: Application of proton chemical shift patterns

Dimesitoate esters of α,α-dibutyl-2,5-tetrahydrofurandimethanols of different relative stereochemistry showed unique chemcial shift patterns in benzene-d6, which is applicable to the assignment of relative stereochemistry of the mono-tetrahydrofuranyl moiety of cytotoxic polyketides.

New Cytotoxic Fatty Acid from Desmos cochinchinensis (Annonaceae)

Abstract Desmosic acid, a novel cytotoxic fatty acid, was isolated from Desmos cochinchinensis Lour. (Annonaceae). Its structure was established by spectroscopic and chemical methods.

Stereochemistry of mono-tetrahydrofuranyl moiety in cytotoxic polyketides. Part A: Synthesis of model compounds

Dimesitoate esters of α,α-dibutyl-2,5-tetrahydrofurandimethanols of different relative stereochemistry were prepared. They serve as model compounds for a 1H-NMR-based stereochemical analysis of the mono-tetrahydrofuranyl moiety of cytotoxic polyketides.

Dasytrichone, A Novel Flavone From Dasymaschalon Trichophorum With Cancer Chemopreventive Potential

Abstract Dasytrichone, A Novel Flavone With An Unusual A-Ring Substitution Pattern Was Isolated From The Stems And Leaves Of Dasymaschalon Trichophorum Merr. (Family Annonaceae). Its Structure Was Established By Spectroscopic Methods And Single Crystal X-Ray Crystallography. Dasytrichone Inhibits The Metabolism Of The Carcinogen Benzo[A]Pyrene By Hamster Embryo Cell Cultures, Suggesting That It Warrants Further Evaluation As A Potential Chemopreventive Agent.

Three New Cytotoxic Norditerpenoid Dilactones from Podocarpus Purdieanus Hook

Abstract Three new cytotoxic norditerpenoid dilactones, purdilactones A {1}, B {2} and C {3}, were isolated from the alcoholic extracts of Podocarpus purdieanus Hook. These compounds exhibited in vitro cytotoxicity in 9PS mouse lymphocytic leukemia and in human tumor cell lines A-549 (lung carcinoma), MCF-7 (breast adenocarcinoma) and HT-29 (colon adenocarcinoma).

New Cytotoxic Cycloartane Triterpenoids From Desmos Cochinchinensis (Annonaceae)

Abstract Desmosinol, a novel cycloartane triterpenoid was isolated from the stem of Desmos cochinchinensis Lour. (Annonaceae). Its structure was established by spectroscopic methods.