Structure Activity Relationship(SAR) validation of aurora kinase inhibitors towards drug designing and understanding modulation of the kinase activity by means of post translational modifications

Abstract

Cell cycle is a set of intricate events that lead to the exact duplication of a cell into two daughter cells and its existence is vital for the propagation of life. To ensure the fidelity of this life preserving process, there are certain guards assigned at each gate. As one event leads to another, certain kinases that come under “cell cycle core kinases” act as engines to propagate the cell from one phase to another whereas a group of proteins clubbed together as “checkpoint proteins”, ensure the integrity of the previous event (Fig.1) [1]. Cell cycle is divided into two major phases: Interphase and M phase, of which, the interphase is further divided into G1, S and G2 phases. The cell ensures that no event is repeated or bypassed with the help of cyclins and cyclin dependent kinases. These come under the category of “core cell cycle kinases”. Each phase/event is controlled by a specific cyclin /CDK complex that is present during that particular phase but gets degraded immediately after the completion of the phase. There are a set of checkpoint proteins at the entrance and exit of each phase .Such proteins are called checkpoint proteins and Aurora kinase A and B come under this class of mitotic kinases.