Executive Summary : | Haematological cancers are blood and bone marrow-related disorders characterized by clonal proliferation of blood-forming cells. Current drugs have toxic side effects and ineffectiveness due to cancer resistance. Epigenetic therapies, such as HDAC8 inhibitors, have gained attention for their potential to restore p53 acetylation and induce apoptosis in inv16 AML CD34 cells without affecting normal hematopoietic stem cells. The project aims to identify structural features required for selective HDAC8 inhibition using QSAR, molecular docking, and molecular dynamics, and design novel selective HDAC8 inhibitors. The compounds will be synthesized and characterized using spectroscopic techniques NMR, MS, and IR. The project will also conduct isoform selectivity HDAC8 assays and in vitro cytotoxicity assays. The project aims to establish a platform for developing hydroxamates as anticancer agents for haematological cancer, combining molecular modeling approaches with experimental studies like synthesis. The results of this research proposal will be of immense importance in academic research and anticancer drug discovery and development. |