The structures of over 350 taxane diterpenoids are classified and presented with information on their plant source, yield, melting point, and optical activity. The biotransformations and biosynthesis of the taxoids are also reviewed.

Nanotechnology applied to biological problems represents an emerging field with the potential to offer extremely sensitive diagnostics and targeted cancer therapies. However, to achieve these goals, nanoparticle delivery systems must outwit the many barriers that are intrinsic to the body's defenses, as well as those that develop during the growth and progression of tumors. The science is advancing and, for example, true nanoscale tumor-targeted drug delivery vectors are now able to reduce the likelihood of opsonization in the bloodstream and uptake by the reticuloendothelial system. Other advances hold promise for delivering multiple therapeutic agents to non-homogeneous populations of cancer cells in solid tumors. We briefly summarize herein our attempts to build such multifunctional nanotherapeutics using colloidal gold nanoparticles. Specifically we discuss the development of colloidal gold-based drugs that are designed to target the delivery of TNF and paclitaxel to solid tumors. Drug Dev. Res. 67:47-54, 2006.

This review provides an overview of the discovery, structures, and biological activities of anticancer natural products which act by inhibiting or promoting the assembly of tubulin to microtubules. The emphasis is on providing recent information on those compounds in clinical use or in advanced clinical trials. The vinca alkaloids, the combretastatins, NPI-2358, the halichondrin B analog eribulin, dolastatin 10, noscapine, hemiasterlin, and rhizoxin are discussed as tubulin polymerization inhibitors, while the taxanes and the epothilones are the major classes of tubulin polymerization promoters presented, with brief treatments of discodermolide, eleutherobin, and laulimalide. The challenges and future directions of tubulin-interactive natural products-based drug discovery programs are also discussed briefly.

The history of the development of the important anticancer drug taxol (1) is briefly described, and recent studies of its chemistry and tubulin-binding conformation are then presented. Topics discussed include side chain attachment to baccatin III (3a), the effect of oxygenation of the taxane ring system on bioactivity, the importance of the oxetane ring for bioactivity, the synthesis of a C-6/C-4 bridged analogue, and the conformation of the side chain when taxol is bound in a complex with polymerized tubulin.

Photoaffinity labeling methods are being used to define the molecular contacts between taxol and its target protein, tubulin. Our laboratory has demonstrated previously that [3H]3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin (Rao, S., Krauss, N.E., Heerding, J.M., Swindell, C.S., Ringel, I., Orr, G.A., and Horwitz, S.B. (1994) J. Biol. Chem. 269, 3132-3134). The interaction of a second photoaffinity analogue of taxol, [3H]2-(m-azidobenzoyl)taxol, with tubulin has been investigated. This analogue specifically photolabels beta-tubulin and the photolabeling is completed by both taxol and unlabeled 2-(m-azidobenzoyl)-taxol indicating a common binding domain. To identify the site(s) of photoincorporation, [3H]2-(m-azidobenzoyl)taxol-photolabeled beta-tubulin was subjected to sequential cyanogen bromide and tryptic digestions. Radiolabeled peptides were purified by reverse phase high performance liquid chromatography, and amino acid sequencing studies identified a peptide containing amino acid residues 217-231 of beta-tubulin as the major photolabeled domain.