Biotransformation and tumor multidrug resistance reversal potency of polyoxygenated taxadienes

The biotransformation of four taxadienes, 2α,5α-diacetoxy-14β-hydroxy-10β-methoxytaxa-4(20),11(12)-diene (1), 10β-methoxy-2α,5α,14β-triacetoxytaxa-4(20),11(12)-diene (2), 2α,5α,10β-triacetoxytaxa-4(20),11(12)-dien-13-one (3), and 2α,5α-diacetoxy-10β-methoxytaxa-4(20),11(12)-dien-13-one (4) were individually investigated by the cultured cells of Ginkgo biloba. Six new metabolites together with four known metabolites were obtained from their biotransformations. Most compounds were evaluated for the MDR reversal activity against taxol-resistant human non-small cell lung cancer (NSCLC)-lung adenocarcinoma cell line, A549/taxol. Two compounds, 5 and 6, exhibited significant MDR reversal activity when co-administered with taxol at 5 μM. The result showed that the methoxyl group at C-10 and hydroxyl group at C-14 may be potential pharmacophores with taxadiene MDR reversal agents.