Executive Summary : | The proposed project aims to develop new anti-sickling agents to overcome the adverse effects of existing treatments, particularly for pregnant women carrying sickle cell disease. The study aims to reduce vaso occlusions, pain, leg ulcers, infection severity, and asthmatic attack episodes, primarily by addressing the root cause of sickle cell disease: polymerization of sickle hemoglobin. The proposed work involves literature review, compound design, synthesis, physiochemical characterization, toxicity studies, and pharmacological evaluation using appropriate in vivo or in vitro models. Ethical committee permission will be obtained before human blood or cell line experimentation. In vivo studies were conducted on human K562 cells, examining cell growth, erythroid differentiation, oxidative stress in red blood cells (RBCs), Fe2 / Fe3 ratio of HbSS, and polymerization of RBCs. Cells were cultured in RPMI-1640 medium, and chemical inducers were added. Oxidative stress was tested to evaluate the prevention or treatment effects of free radicals. The Fe2 / Fe3 ratio of HbSS was determined using a method. The polymerization effect of HbS was observed in a deoxygenated environment using sodium metabisulphite. |