The structural pharmacophore of Taxol, responsible for binding the N terminus of the beta-subunit of tubulin to arrest cell proliferation, comprises, in part, the 13-O-(N-benzoyl-3-phenylisoserinoyl) side chain. To identify the side chain transferase of Taxol biosynthesis, a set of transacylases obtained from an enriched cDNA library (constructed from mRNA isolated from Taxus cuspidata cells in...

BACKGROUND AND AIMS Hydration, rupture and exine opening due to the sudden and large expansion of intine are typical of taxoid-type pollen grains. A hemispheric outgrowth external to the exine was observed on Cupressus and Juniperus pollen grains before the intine swelling and exine release. However, the actual existence of this permanent or temporary structure and its precise role in pollen hy...

Cyclostreptin (FR182877), a bacterial natural product, was reported to have weak paclitaxel-like activity with tubulin but antitumor activity in vivo. We used synthetic cyclostreptin in studies of its mechanism of action. Although less potent than paclitaxel in several human cancer cell lines, cyclostreptin was active against cells resistant to paclitaxel and epothilone A. At equitoxic concentr...

Obtainment and characterization of the novel endosperm callus of Taxus chinensis Rehd. var. mairei are valuable for haploid breeding, genome, and functional genome in Taxus. Callus was obtained by hydropriming with sterile water for 3 days and suitable medium composition. The highest callus induction (70.89 %) and lower browning ratio (7.95 %) were obtained from Gamborg (B5) medium supplemented...

Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two warheads, self-immolative disulfide linkers for drug release, biotin as the tumor-targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR...

Peloruside A (peloruside), a microtubule-stabilizing agent from a marine sponge, is less susceptible than paclitaxel to multidrug resistance arising from overexpression of the P-glycoprotein efflux pump and is not affected by mutations that affect the taxoid binding site of beta-tubulin. In vitro studies with purified tubulin indicate that peloruside directly induces tubulin polymerization in t...

Laulimalide, a natural product from marine sponges, is a microtubule-stabilizing agent that binds to tubulin at a site distinct from that of the taxoids. In the present study, we found that laulimalide inhibited human umbilical vein endothelial cell (HUVEC) tubule formation and vascular endothelial growth factor (VEGF)-induced HUVEC migration, key components of the angiogenic process. These occ...

Plants have been important in healing human disease for millennia. Herbal medicines have served human cultures worldwide, and have also been important sources of modern pharmaceuticals. Specific phytochemical groups from higher plants have been the sources of the bulk of natural product drugs used in biomedicine (Raskin et al., 2002). The plant-derived alkaloids that are widely used as drugs in...

Biosynthesis of the anticancer drug Taxol involves 19 enzymatic steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methylerythritol phosphate pathway for isoprenoid precursor supply. To gain further insight about Taxol biosynthesis relevant to the improved production of this drug and to draw inferences about the organization, regulation, and ori...