Structure-Based Drug Design and Combinatorial Chemistry in the Search of Antimitotic Agents

Mitosis is considered as the main stage of the cell division process. It is well established that abrogation of the normal mitotic progression is a highly efficient concept for anti-cancer treatment. The current therapeutic arsenal available to fight againist cancer is comprised of drugs that can act at different levels and on different targets. Among them, antimitotic drugs have received special attention during decades due to the clinical success of drugs such as vinca alkaloids or taxanes, among others. In the last decade, a new generation of targeted antimitotic agents (different to classical cytotoxic drugs that act directly on microtubules) has been investigated in depth. These new promising therapies include inhibitors of kinase family members such as Aurora, Polo, CDKs, the mitotic spindle assembly checkpoint (SAC) kinases, among others, as well as important enzymes such as the kinesins CENP-E or KSP and phosphatases (PP1, PP2A, and Cdc25). This CTMC special issue is devoted to review the current state of the art in the search for active antimitotics in some different mitotic targets mentioned above, by using integrated approaches such as High Troughput Synthesis and Combinatorial Chemistry, particularly the use of targeted multicomponent reactions (MCRs), as well as protein–ligand X-ray crystallography, NMR spectroscopy and Molecular Modelling (structure-based drug design using docking, QSAR, etc), providing valuable insight into protein–ligand interactions by informing and accelerating the iterative process of inhibitor design.