Natural Products and Derivatives as Leads to Cell Cycle Pathway Targets in Cancer Chemotherapy

David   J.   Newman; Gordon   M.   Cragg; Susan      Holbeck; Edward   A.   Sausville

doi:10.2174/1568009023333791

Abstract

The influence of natural products upon drug discovery in general has been quite impressive, one only has to look at the number of clinically active drugs that are in use in cancer therapy to see how many either are natural products or have a natural product pharmacophore. What is now becoming quite apparent is that materials from natural sources are excellent probes (indicators) for cellular targets that when modulated, may well have a deleterious effect upon the cycling of a tumor cell through the conventional cell cycle. If the particular target is not expressed in normal cell cycling, then a directed “perturbation” of the tumor cells cycle may well lead to a novel method of treatment for specific tumor types. In this review we have not attempted to be exhaustive but have given a current overview of how natural products from marine, microbial and plant sources have permitted in-depth analyses of various parts of the cell cycle under varying conditions with the ultimate aims of attempt ing to “control or perturb” the cycling of tumor cells in a fashion that permits their ultimate removal via cellular death, with a minimum of trauma to the host.

Keywords: Cancer Chemotherapy, Cyclin-dependent Kinase Inhibitors, Checkpoint Inhibitors, Phosphatases, Tubulin