Current Pharmaceutical Design - Volume 7, Issue 13, 2001

Vinca alkaloids represent a chemical class of major interest in cancer chemotherapy. The lead compounds vinblastine and vincristine have been employed in clinical practice for more than thirty years and remain widely used to this day. Several hundred derivatives have been synthesised and evaluated for their pharmacological activities, the majority being modified in the vindoline moiety, bearing several reactive centers. The Read More

The pharmacological profile of vinflunine, a novel bi-fluorinated derivative of vinorelbine is summarised. Detailed comparisons, based on in vitro and in vivo experimental preclinical data, of vinflunine with its parent molecule and the classic Vinca alkaloids, exemplified by vincristine or vinblastine, have revealed certain qualitative and quantitative differences between these first and second generation Vincas. Evidence is Read More

(250 words): A diverse group of natural biological compounds bind to microtubules and suppress microtubule dynamics. Here we review the mechanism of microtubule assembly and dynamics as well as structural features that are important for nucleotide binding, GTP hydrolysis and stabilization of longitudinal and lateral protofilament contacts. Specific emphasis is placed upon the polar structure of the microtubule, t Read More

The antimitotic agents of the Taxoid series are important substances as anticancer drugs. The efficacy of paclitaxel (Taxol) and docetaxel (Taxotere) has been well demonstrated in the treatment of breast, ovarian and lung cancers. Although these drugs have brought benefits in cancer chemotherapy, they unfortunately possess some disadvantages due to their inefficacy on certain resistant cancers, and due to their toxi Read More

Paclitaxel and docetaxel are two key molecules in the treatment of a variety of cancers with major impact in the treatment of breast, lung and ovarian cancers.A number of taxoids have then been synthesized in an effort to improve some of the features of the existing drugs. Although the literature is still scant of preclinical data due to the highly competitive field, several compounds are already in clinical trials. Most of thes Read More

The antitumor cryptophycins are synthetic derivatives of the desipeptide cryptophycins isolated from the cyanobacterium Nostoc sp. Cryptophycin 52 that is currently in clinical trial in solid tumors, is prepared by total synthesis of four key fragments that are coupled to form the final product. The mechanism of anticancer activity of the cryptophycins has been associated with their destabilization of microtubules and with their i Read More

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 Read More

Recently identified novel agents that disrupt tubulin polymerization include synthetic spiroketal pyrans (SPIKET) targeting the spongistatin binding site of beta tubulin. These agents exhibit anticancer activity by disrupting normal mitotic spindle assembly and cell division as well as inducing apoptosis. At nanomolar concentrations, the SPIKET compound SPIKET-P caused tubulin depolymerization in cell-free turbidity assays an Read More

Besides the many recognised compounds described and detailed in the present issue including the Vinca alkaloids, the taxanes, certain cryptophycines, epothilones and eleutherobines, several new products interacting with tubulin are identified regularly in the literature. These products may have been isolated from natural sources (plants, marine organisms, bacteria), but also more recently combinatorial, or at Read More