Ligand-based Virtual Screening of Phenanthrene-9,10-dione as a Potential Drug Lead against Sickle Cell Disease through in-silico Identification

Abstract

One of the illnesses afflicting some people worldwide is sickle cell disease which transcends national and ethnic boundaries. In this study, similar compounds from phenanthrene-9,10-dione were obtained using the SwissSimilarity prediction model with fingerprint and pharmacophore as the screening methods. Nine similar compounds were obtained with a similarity score ranging from 1.0 to 0.75. These compounds were subjected to SwissADME and optimized with DFT. Four out of the nine compounds failed ADMET studies. The remaining five compounds with good DFT and ADMET properties were subjected to molecular docking and molecular dynamic simulations. 3-phenylphenanthrene-9,10-dion 3-phenylphenanthrene-9,10-dione (A9-4) had the best binding affinities with the three proteins; A9-4 had -11.0 kcal/mol, -10.9 kcal/mol, and -8.0 kcal/mol, compared to Rivaroxanban binding affinities of -8.5 kcal/mol, -8.1 kcal/mol, and -8.0 kcal/mol with crystal structure and binding pocket of Carbonmonoxy Sickle Hemoglobin in R-State Conformation, crystal structure and binding pocket of carboxyhemoglobin and crystal structure and binding pocket of destabilize sickle hemoglobin polymer formation (PDB IDs 5E6E, 6BWU, and 6D14), respectively. Molecular dynamic simulations showed that the complex formed between the protein and 3-phenylphenanthrene-9,10-dione (A9-4) is more stable than the complex formed with Rivaroxanban.