A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis.

Oxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus×media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α-hexaacetoxytaxa-4(20),11(12)-diene (1) as a substrate led to the production of a major oxetane derivative, 1β-dehydroxybaccatin IV (1 a), and a minor 4β,20-epoxide derivative, baccatin I (1 b). However, feeding the substrate decinnamoyltaxinine J (2), a 5-deacetylated derivative of 1, yielded only 5α-deacetylbaccatin I (2 b), a 4β,20-epoxide.

Exploring the catalytic diversity of two short-chain dehydrogenases/reductases from .

Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from 3.5365.

Functional Characterization and Cyclization Mechanism of a Diterpene Synthase Catalyzing the Skeleton Formation of Cephalotane-Type Diterpenoids.

CsCTS, a new diterpene synthase from Cephalotaxus sinensis responsible for forming cephalotene, the core skeleton of cephalotane-type diterpenoids with a highly rigid 6/6/5/7 tetracyclic ring system, was functionally characterized. The stepwise cyclization mechanism is proposed mainly based on structural investigation of its derailment products, and further demonstrated through isotopic labeling experiments and density functional theory calculations. Homology modeling and molecular dynamics simulation combined with site-directed mutagenesis revealed the critical amino acid residues for the unique carbocation-driven cascade cyclization mechanism of CsCTS.

Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.

With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid.

Design, Synthesis, and Cytotoxic Analysis of Novel Hederagenin⁻Pyrazine Derivatives Based on Partial Least Squares Discriminant Analysis.

Hederagenin () is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new ⁻pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines The majority of these derivatives showed much stronger cytotoxic activity than . Remarkably, the most potent was compound (half maximal inhibitory concentration (IC) was 3.

Neuroprotection by new ligustrazine-cinnamon acid derivatives on CoCl-induced apoptosis in differentiated PC12 cells.

A new series of ligustrazine-cinnamon acid derivatives had been designed and synthesized as potential neuro-protective agents. Among the derivatives, 3a exhibited the promising neuroprotective activity (EC = 3.68 μM).

A New Oleanolic Acid Derivative against CCl₄-Induced Hepatic Fibrosis in Rats.

A novel hepatoprotective oleanolic acid derivative, 3-oxours-oleana-9(11), 12-dien-28-oic acid (Oxy-Di-OA), has been reported. In previous studies, we found that Oxy-Di-OA presented the anti-HBV (Hepatitis B Virus) activity (IC = 3.13 µg/mL).

Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents.

The lead compound TBA, 3β-Hydroxy-lup-20(29)-ene-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester, which exhibited promising antitumor activity and induced tumor cell apoptosis in various cancer cell lines, had previously been reported. Moreover, reports have revealed that the introduction of amino acid to betulinic acid could improve selective cytotoxicity as well as water solubility. Thus, a series of novel TBA amino acid and dipeptide derivatives were designed, synthesized and screened for selective cytotoxic activity against five cancer cell lines (HepG2, HT-29, Hela, BCG-823 and A549) and the not malignant cell line MDCK by standard MTT assay.