ABSTRACT Breast cancer remains a significant global health concern, highlighting the need for the development of new therapeutic strategies. This study presents the design and synthesis of a novel series of chiral thiazoles (8a–8i) using an efficient synthetic route, achieving good yields (75%–98%). These compounds are explored as potential inhibitors targeting AKT1, a crucial player in the progression of breast cancer. The synthesized compounds were thoroughly characterized using high‐resolution mass spectrometry and nuclear magnetic resonance (HRMS and NMR) spectroscopy. A comprehensive network pharmacology approach was employed to investigate potential target genes for the thiazoles ( 8a–8i) in breast cancer. This analysis successfully identified AKT1 as a crucial target for these compounds. The AKT1 gene plays a significant role in the growth and proliferation of cancer cells. Therefore, one objective of this study is to inhibit AKT1 using the newly prepared (8a–8i) to prevent cancer cell growth and ultimately induce their death. The thiazoles (8a–8i) were screened for ADMET properties and molecularly docked against the AKT1 target. Molecular dynamics simulations (RMSD and RMSF values) were conducted for the two lead compounds over 100 ns to assess their stability. All designed compounds exhibited favorable physicochemical and ADMET properties. Among them, ( 8b , 8d) were identified as novel lead molecules targeting AKT1.
Amri et al. (Thu,) studied this question.