Showing papers in "Progress in the chemistry of organic natural products. Progrès dans la chimie des substances organiques naturelles in 2002"

The chemistry of taxol and related taxoids.

Abstract: The anticancer compound taxol (1.1.1) was originally isolated in the late 1960’s from the bark of the Western Yew, Taxus brevifolia, and its structure was published in 1971 in a paper that has been cited well over 1000 times since its publication (1). Taxol was originally isolated on the basis of its cytotoxicity and antileukemic activity, but it was not actively developed as a drug for several years because of its scarcity (the initial yield from yew bark was 0.02%) and because of its lack of water-solubility. Fortunately additional testing at the National Cancer Institute revealed its activity against various human solid tumor xenografts in nude mice, and a program to develop taxol as a drug was initiated in 1977. A key discovery from the Horwitz laboratory in 1979, in a paper that has also been cited over 1000 times since its publication, showed that taxol had a unique mechanism of action, binding to polymerized tubulin and stabilizing microtubules to dissociation (2). These twin discoveries of taxol’s activity and its mechanism of action provided the impetus for continued clinical trials in the face of some initial disappointments, and the first positive clinical results against ovarian cancer were announced in 1989 (3). Following these results taxol was also found to be effective against breast cancer (4) and was licensed to Bristol-Myers Squibb; its sales are estimated at $1.6 billion in 2000 (5).

Naturally occurring cyclic tetrapyrroles.

Abstract: Of the porphyrinoid structures occurring in nature the most important and most widespread are the red blood pigment heme (1), the green pigment of plant photosynthesis chlorophyll a (2), the bacterial photo-synthetic pigment bacteriochlorophyll a (3), and the “antipernicious” red pigment vitamin B12 (4). The basic function of these cofactors are determined by the incorporation of the different metal ions into the macrotetracycles. The different oxidation levels of the macrocyclic ligand system regulate the fine tuning of these functions. The final adaptation of the cofactors to their special molecular environments in the cell compartments is effected by variation of the substitution patterns of the chromophores.