Current Pharmaceutical Design - Volume 11, Issue 13, 2005

Epothilones A and B are naturally occurring microtubule-stabilizers, which inhibit the growth of human cancer cells in vitro at nM or even sub-nM concentrations. In contrast to paclitaxel (Taxol®) epothilones are also active against different types of multidrug-resistant cancer cell lines in vitro and against multidrug-resistant tumors in vivo (epothilone B). Their attractive preclinical profile has made epothilones important lead str Read More

The macrocylic polyketide class of compounds known as the epothilones has generated substantial interest over the last few years in the areas of chemistry, biology, and medicine due to their interesting structure and, more importantly, their activity against numerous cancer cell lines, including drug-resistant, especially Taxol®-resistant, cancer cell lines. To date, numerous total syntheses have been published, hundreds Read More

The design of novel anticancer agents based on the combretastatins, a group of antimitotic agents isolated from the bark of the South African willow tree Combretum caffrum Kuntz, is of considerable contemporary interest. Combretastatin A-4, the most active compound in the group, due to its unique dual features of antitubulin and antivascular properties, has drawn significant attention of medicinal chemists for the desig Read More

The development of combretastatin as an antimitotic agent has led to an enormous effort to design other tubulin-targeting agents. The intriguing discovery that combretastatin A-4 phosphate causes selective damage to tumor vasculature has stimulated even more activity in this field. This attention to tubulin binding agents and their antivasculature activity is highly likely to lead to significant clinical advances for the treatme Read More

Podophyllotoxin is an antimitotic natural product. Its inhibitory activity on cell growth led to the development of the clinically valuable anticancer agents, etoposide, teniposide and the water-soluble prodrug, etoposide phosphate. The cytotoxic mechanism of these drugs is the inhibition of topoisomerase II, unlike the lead compound which inhibits mitosis. Through extensive structure-activity relationship studies, several pote Read More

Natural product drugs that target the tubulin/microtubule system remain an important component in the therapeutic arsenal to treat many types of malignancies. Agents such as the taxanes and vinca alkaloids bind to β-tubulin and disrupt microtubule dynamics by inducing a potent mitotic block and subsequent cell death. Understanding why certain cancers do not respond to treatment or develop resistance has been the subject Read More