1,3,4-Oxadiazole-based EGFR inhibitors as anticancer therapeutics: SAR study and binding mode of interaction analysis

In recent years, cancer has emerged as a significant challenge to the healthcare system, and medicinal researchers are tirelessly working to develop new potential medications to combat this disease. Despite the progress in the diagnosis of the pathophysiology of cancer and several treatment options, it is still the leading cause of death in the 21st century. Researchers have explored numerous molecular targets of cancer, including various protein kinases, phosphatases, and proteins regulating cell cycle and apoptosis. In the meantime, tyrosine kinases (TKs) have evolved as the key enzymes involved in the pathogenesis of solid tumours. Among them, EGFR or ErbB1 has been implicated in several cancers like cancer of the lungs, breast, cervical, liver, colorectal, etc. A fascinating approach to cancer treatment involves inhibiting the expression of EGFR or HER1 TK. The 1,3,4-oxadiazole scaffold is a crucial heterocycle that serves several medicinal roles, including cancer treatment. In the last decade, 1,3,4-oxadiazole hybrids have shown potential as anticancer agents by inhibiting EGFR expression and function. This study delves into the advancement of 1,3,4-oxadiazole-based EGFR inhibitors with SAR studies and their binding mode of interaction analysis. Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with 1,3,4-oxadiazole-based EGFR inhibitors for anti-cancer action. • Recent findings on 1,3,4-oxadiazole hybrids as synthetic EGFR antagonists are extensively covered. • Potent hybrid molecules and their SAR findings are presented in detail. • Identified the most promising compounds from each category of 1,3,4-oxadiazole hybrid molecules. • This study may assist in designing potential synthetic EGFR antagonists in future.