QSAR and Structure-Based Docking Studies of Aryl Pyrido[2,3-d]pyrimidin-7(8H)-ones: An Attempt to Anticancer Drug Design

Introduction

Cancer is a state of uncontrolled growth and abnormal proliferation of cells due to loss of normal mitotic cell division mechanism combined with malignant behavior of the cells. Normal division of cells takes place by mitotic cell division process through which a cell is evenly divided into two daughter cells having same number of chromosome as of parent. The mitosis consists of two phases such as interphase and M phase. Interphase is also called as preparatory phase. In this phase cytochrome and nucleus do not divide but the cell is prepared to divide. It takes place in three phases which are G1, S, and G2. The G1 phase is also called as growth phase. The proteins and enzymes essential for synthesis phase are produced in this phase. The S phase represents the synthesis phase. Each human cell contains 23 pairs of chromosomes (1 pair of sex chromosome and 22 pairs of autosomes). The DNA synthesis occurs during which all chromosomes are copied and the number of DNA in cell becomes double. Synthesis of microtubules takes place in G2 phase which is crucial for mitosis phase. During M phase, protein synthesis stops and chromatids are attached to microtubules. This phase is processed as prophase, metaphase, anaphase and telophase. After M phase, cytokinesis occurs and a cell divides into two cells (Waugh & Grant 2006). The checkpoint systems including G1, G2 and spindle assembly checkpoints play a major role in normal cell division process. These checkpoints stimulate the enzyme system to repair DNA damage if there is lack of chromosomes as well as it can stimulate apoptosis process for programmed cell death if there is excessive formation of chromosomes (Satyanarayana & Chakrapani 2013).