Paclitaxel antitumor natural product

Although not listed in the tables, at least four other natural product drugs have given yeoman service in the antitumor area. The first of these is paclitaxel (Taxol ) which sold US 1.6 billion in 2000 this is followed by the vinca alkaloids vinblastine and vincristine. Completing the quartet are the natural product-derived epi-podophyllotoxin derivatives teniposide and etoposide and the materials derived from camptothecin, topotecan and CPT-11. These will probably not be the only natural product drugs in the antitumor field, as can be seen by inspection of Table 6.3, where Cragg and Newman recently reported on the source... 

As one of the most successful antitumor drugs, paclitaxel (Taxol ), a diterpenoid natural product, was originally isolated in the bark of the Pacific yew tree Taxus... 

The clinical success of Paclitaxel has stimulated research into compounds with similar modes of action with antineoplastic efficacy while minimizing its less desirable properties, such as water insolubility, difficult synthesis, and emerging resistance. The epothilones are a novel class of natural product cytotoxic compounds derived from the fermentation of the Sorangium cellulosum, which are non-taxane microtubule-stabilizing compounds that trigger apoptosis [182-189]. The natural product epothilone B 144 (Figure 4.39) has demonstrated broad-spectrum antitumor activity... 

Paclitaxel (Taxol, NSC-125973), obtained from Taxus species, is a diterpene with intense antitumoral activity because of its tmique mode of action on the microtubular cell system. It is one of the most successful anticancer drugs developed in the past 50 years. Due to several difficulties associated with obtaining Taxol and related taxoids firom plants growing in nature, plant cell cultures are considered to be the most favorable and environmentally sustainable approach for its production of at an industrial level. Some pharmaceutical companies, such as the... 

Several p-amino acids occur naturally as free metabolites in metabolic pathways or as key intermediates in biosynthetic products. p-Alanine is the simplest p-amino acid that appears in pantothenic acid, a precursor of the coenzyme A. Further examples are (2R,3S)-N-benzoyl-3-phenylisoserine derived from (R)-p-phenylalanine, a compound in the antitumor agent paclitaxel from Taxus brevifolia [89], or as building blocks for p-lactam antibiotics [90] and in jasplakinolide, an antifungal compound [91] (Scheme 29.12). 

Paclitaxel (Taxol) 57, a natural terpenoid product derived from the bark of the Pacific yew Taxus brevifolia [83-85], and its hemisynthetic analog docetaxel (Taxotere) 58, are two recently discovered promising antitumor agents. At this moment, very few data have been published about the microbial metabolism of taxoid compounds only site-specific hydrolyses of acyl side chains at C-13 or C-10 by extracellular and intracellular esterases of Nocardioides albus SC 13911 and N. lutea SC 13912, respectively, have been reported [86]. On the other hand, Hu et al. [87-89] recently described some fungal biotransformations of related more abundant natural taxane diterpenes extracted from Chinese yews or their cell cultures, in order to obtain new active substances or precursors for hemisyn-thesis of paclitaxel analogs. 

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