Leveraging on Computational Strategies to Alleviate Vaso-Occlusive Crises in Sickle Cell Disease

Sickle Cell Disease (SCD) is among the most common inherited disorders, associated with significant morbidity and mortality. The abnormal sickle-shaped red blood cells obstruct blood flow in small vessels, causing vaso-occlusion that results in ischemia, inflammation, acute painful crises, tissue injury, and progressive organ damage. The study aims to identify bioactive compounds that has the potential of combatting SCD computationally.

Prediction of Activity Spectra of Substances Database was used to identify thirty-four compounds that had likelihood of being predicted to manage SCD. The SwissAdmet and Pro-tox II tools were utilized for ADMET profiling, thirty-eight (38%) of the thirty-four compounds possessed good ADMET studies and were optimized at DFT, docked with Carboxyhemoglobin, (PDB ID: 6BWU) and destabilize sickle hemoglobin polymer formation (ID: 6DI4) and rivaroxaban.

The results from molecular descriptions implied that compounds A23, A28, A33, A34, A37, and A37 were very disposed to stronger interactions with the receptors, docking and molecular dynamic simulations results revealed that compounds 2-[3,4-bis(phenylmethoxy)phenyl]ethanamine (A23), N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]benzamide (A28), 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (A37) had − 9.4, -8.6 and − 8.6 kcal/mol binding scores, respectively with 6D14 receptor while the rivaroxaban had 8.0 kcal/mol. Likewise, 2-[3,4-bis(phenylmethoxy)phenyl]ethanamine (A23), N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]benzamide (A28) had − 9.7 and − 8.7 kcal/mol, respectively with 6BWU receptor while the rivaroxaban had 8.6 kcal/mol.

In conclusion, compounds A23, A28 and A37 showed a stronger therapeutic potential than rivaroxaban.