Design, Synthesis and Anti‐Sickling Activity of some Novel Analogs of Isoindoline‐1,3‐dione

Sickle cell anemia is a prevalent genetic hematological disorder spread all over the world, having severe complications and high morbidity and mortality. Disease-carrying individuals have a very short life span; medications and treatments available are only symptomatic, not curative. In an effort to find novel substances and targets that can either prevent or treat the underlying cause of illness, we used molecular docking and comparative analysis of docking scores with three software programs, molecular dynamics (MD) simulation, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies to analyze the interactions of novel analogs of phthalimide, as it has proved better anti-sickling activity. One compound's MD potential into hemoglobin S's active site was examined as it had the highest score, with a binding energy of -11.6 kcal/mol selected through AutoDock Vina software, and further validation and accuracy docking scores were calculated through Molegro Virtual Docker (MVD) software and Schrodinger software. Phthalimide was determined to have the best binding energy of P1 among the 32 new medications created on the basis of its parent, followed by P2 with a binding energy of -11.6 kcal/mol and P15 with a binding energy of -10.2 kcal/mol. The docking results were validated with the aid of MD simulations, with an RMSD of the ligand-fit protein stable at 40 ns throughout the simulation within 0.6-4.2 Å. For the prediction of carcinogenicity, the SwissADMET web-based service was able to predict the BBB role for the designed drugs, Lipinski's guideline was followed for the created medications, and bioavailability was determined. The chemicals biological actions were understood as a result of the high scores, and later they were synthesized in a wet lab and assessed for their pharmacokinetic and pharmacodynamic properties for their efficacy, showing anti-sickling activity. The synthesized compound demonstrates better significant anti-sickling activity by reducing polymerization and the least toxicity in human SCA blood.