The Epothilones, Eleutherobins, and Related Types of Molecules

Shawn   J.   Stachel; Kaustav      Biswas; Samuel   J.   Danishefsky

Abstract

Taxol is currently one of the most effective anticancer agents available. However, limitations due to multidrug-resistance (MDR) susceptibility and lack of aqueous solubility render it less than an ideal drug. These limitations, coupled with taxols unique mechanism of tumor inhibition, involving the stabilization of microtubule assembly, have spurred the search for more effective chemotherapeutic agents. This review will discuss the chemistry and biology of some of the most promising new molecules with taxol-like activity. The extended family of microtubule-stabilizing agents now includes the epothilones, eleutherobins, discodermolide, laulimalide and WS9885B. The epothilones have emerged as one of the most exciting new candidates for detailed structure-activity-related studies. A review of our efforts in the synthetic and biological aspects of this research is presented, as are the latest developments reported from other laboratories in academia and the pharmaceutical industry. The synthesis and str ucture-activity studies of eleutherobins, as well as recent progress with discodermolide, laulimalide and WS9885B are also reviewed. An abundance of exciting advances in chemistry and biology have emerged from these studies, and it is hoped that it will ultimately result in the development of new and more effective chemotherapeutic agents in the fight against cancer.

Keywords: Epothilones, Eleutherobins, discodermolide laulimalide, epothilones eleutherobins, Chemotherapy, multiple-drug-resistance (MDR), Sorangium cellulosum, Phytophotora