Designing novel molecule (V-NNC) based on Voxelotor (GBT-440) against sickle cell disease (SCD) via binding to carbonmonoxy hemoglobin S

Sticking cell disease is a defect in hemoglobin structure that leads to deficiency in oxygen transferring to tissues. Voxelotor is a new compound that achieved FDA-approved to treat SCD, recently. In this study, we aimed to introduce novel structure based on the voxelotor to cure the mentioned condition more effectively. At the beginning, various properties of Voxelotor including electronic properties, reactivity and stability were assessed via B3LYP/6-311++G(d,p) method and Global Reactivity in said method that revealed Voxelotor is a stable compound with low reactivity. In addition, docking potential of Voxelotor into active site of hemoglobin S was investigated. Then, several molecules were designed and optimized based on the Voxelotor structure. Docking and physicochemical properties of investigated molecules were analyzed. Results of presented study revealed that between four molecules (V-NNC, V-NNN, V-CNC and V-CNN) with higher potential to interact with Hemoglobin S in comparison with Voxelotor, only V-NNC has the optimum physicochemical features. So, molecular structure screening and evaluating of Voxelotor and designing novel compounds based on it leads to introducing an optimized molecule with suitable potential to treat SCD.