Designing strategies, structural activity relationship and biological activity of recently developed nitrogen containing heterocyclic compounds as epidermal growth factor receptor tyrosinase inhibitors

Cancer cells have the ability of dysregulation and autonomous proliferation due to unchecked production of definite molecules. These molecules are involved in the cell growth (growth factor) or through an irregular and boosted expression of specific proteins (growth factor receptors) on the cell membranes to which growth factors selectively bind. Both phenomena activate a sequence of intracellular indications that eventually lead to the proliferation of cancer cells, initiation of angiogenesis, and metastasis. Epidermal growth factor receptor (EGFR) belongs to the growth factor receptors and is commonly expressed in a variety of tumours, including non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, and head and neck cancer. Therefore, EGFR is an important receptor for the treatment which results in the discovery of EGFR tyrosinase inhibitor. There are the number of EGFR TKIs available in the market but none of them proved to be the golden discovery. Initially, EGFR TKIs have high response rates, but due to inherent and acquired resistance as a result of mutation establish a major challenge to the longitudinal treatment. Three generations of EGFR TKIs have been created as a result of resistance and mutations. Osimertinib and other third-generation EGFR TKIs failed due to the emergence of resistance and mutations like C797S. Therefore, researchers are urged of developing novel molecules. Natural compounds always proved to be the potential/lead compounds as EGFR inhibitors. They produced a synergistic effect along with the synthetic molecules. The N-heterocyclic ring system is a core for the design and discovery of synthetic compounds as they exhibit broad range of biological activities. In recent years (2021-2022) N-heterocyclic derivatives were exposed as potential EGFR inhibitors. The present review summarised the research progress of EGFR inhibitors to overcome the restrictions of presently available drugs by understanding the history, anatomy, mutation of EGFR, and its role in different types of cancer. The review also explained the medicinal chemistry perspective in terms of N-heterocyclic compounds, designing strategies, and structureactivity relationships. Our review will support the medicinal chemists in refining and directing the development of novel N-heterocyclic-based EGFR inhibitors.