Effect of Modified Aspirin and Isoxsuprine Analogs on Ischemic Heart Disease

Ischemic heart disease (IHD) or coronary artery disease (CAD) is one of the largest death-causing reasons in developing countries. Approximately, every year 15 million deaths due to IHD are reported worldwide. PLG (Plasminogen), PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9), CXCL12 (C-X-C Motif Chemokine Ligand 12), and EDNRA (Endothelin Receptor type A) genes were selected for the study due to their higher rate of mutations in IHD. Drugs that are being used to cure IHD were reformulated by structurally modifying them for repurposing. Reformulated drugs were further analyzed for side effects, toxicity, and ADMET (Absorption, Distribution, Metabolism, Excreation, Toxicity) properties. Molecular docking studies of reformulated drugs with selected genes were performed to determine their efficacy to cure IHD. Interacting amino acid residues in the docked complex of aspirin were identified as Aspartic acid, Arginine, Tyrosine, Proline, Valine, Alanine, Threonine, Iso Leusine, Lysine, Triptophan, Aspargine, Histadine, Cystine. Similarly, for isoxsuprine the residues were Valine, Aspargine, Leucine, Argining, Iso Leucine, Glutamic acid, Lysine, Glycine, Proline, Threonine, Aspartic acid, Histadine and Arginine. In reformulated compounds, the addition of sulfur in the aspirin compound reduced the toxicity from class 3 to class 5 and in isoxsuprine, the addition of nitrogen hydrogen bond in the second aromatic ring reduced its toxicity from class 3 to class 4. It is suggested that both aspirin and isoxsuprine analogs are more effective having least predicted side effects and toxicities than already existing aspirin and isoxsuprine. In the future, these drugs can be used as potential drugs for the treatment of IHD than original drugs because of their low toxicity and side effects. This study can be validated in vitro to confirm its efficacy.