Review on the Significance of Pyrimidine Derivatives as Potent Anti-Angiogenic Vegfr-2 Inhibitors

Abstract

Cancer is a disease in which human cells grow uncontrollably and spread to other body parts. Cancer is the second leading cause of death globally and accounted for 9.6 million deaths in 2022 according to the statistics of the World Health Organization. Cancer can begin in any part of the human organs when the normal cell loses the ability to control the division cycle, which may inhibit apoptosis. Cancer cells grow and multiply by activating the angiogenetic factors to build new capillaries that can supply tumor tissue with nutrients. Cancerous tumors spread into or invade nearby tissues and can travel to other organs in the body to form new carcinogenic tissue by metastasis. The goal of treatment is control growth of cancer cells, and induction the programmed cell death. Pyrimidines and its derivatives have been found as effective and valuable pharmacophoric units in medicinal chemistry to design and develop a wide range of bioactive compounds. The present review summarizes the advances in lead compounds of pyrimidines hybrids and their related heterocycles in the treatment of cancer. Moreover, the review also helps to intensify the drug development process by providing an understanding of the potential role of these hybridized pharmacophoric features as VEGFR-2 inhibitors. Abbreviations Abbreviation Meaning FGFR1Fibroblast growth factor receptor 1 VEGFR Vascular Endothelial Growth Factor CSF-1RColony stimulating factor 1 receptor NETs Neuroendocrine tumors AKT Protein kinase B (PKB), also known as Akt A549Human lung adenocarcinoma cell line MCF-7Human breast cancer cell line HepG2Human liver cancer cell line Ovcar-3High-grade serous ovarian adenocarcinoma cell line ObjectivesThe aim of this study is to highlight the role of Pyrimidines containing compounds in inhibiting VEGFR-2 as well as to suggest some new aspects of treatment of cancer using pyrimidines scaffold soon.