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Epothilones have received unusual attention over the past ten
years. They are novel antitumor drugs which very much like their
predecessor paclitaxel (Taxol) act via microtubule stabilization.
In comparison to paclitaxel and a number of alternative drugs with
a similar mode of bioaction (e.g. laulimalide, eleutherobin,
peluroside, discodermolide) the epothilones have significant
advantages, above all very high activity in the nanomolar range and
low susceptibility towards multidrug resistance. Epothilone B and
several derivatives thereof are in phase I-III clinical trials; one
of them (ixabepilone, BMS) is already on the market, others are
supposed to appear on the market in the near future. All naturally
occurring epothilones have been isolated from Sorangium cellulosum;
their antitumor action is traced back to the stabilization of
microtubules. In consequence, the formation of the mitototic
spindle is prohibited and the cell undergoes apoptosis.
B. Basler, S. Brandes, A. Spiegel and T. Bach: Total Synthesis of
Kalsoene and Preussin .- R. Bandichhor, B. Nosse and O. Reiser:
Paraconic Acids- the Natural Products from Lichen Symbiont .- M.
Hiersemann and H. Helmboldt: Recent Progress in the Total Synthesis
of Dolabellane and Dolastane Diterpenes .- L. Wessjohann and E.
Ruijter: Strategies for Total and Diversity-Oriented Synthesis of
Natural Product (-Like) Macrolides .- M. Sefkow: Enantioselective
Synthesis of C(8)-Hydroxylated Lignans: Early Approaches and Recent
Advances
Epothilones have received unusual attention over the past ten
years. They are novel antitumor drugs which very much like their
predecessor paclitaxel (Taxol) act via microtubule stabilization.
In comparison to paclitaxel and a number of alternative drugs with
a similar mode of bioaction (e.g. laulimalide, eleutherobin,
peluroside, discodermolide) the epothilones have significant
advantages, above all very high activity in the nanomolar range and
low susceptibility towards multidrug resistance. Epothilone B and
several derivatives thereof are in phase I-III clinical trials; one
of them (ixabepilone, BMS) is already on the market, others are
supposed to appear on the market in the near future. All naturally
occurring epothilones have been isolated from Sorangium cellulosum;
their antitumor action is traced back to the stabilization of
microtubules. In consequence, the formation of the mitototic
spindle is prohibited and the cell undergoes apoptosis.
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