An in-silico Study of 1,2-di(Cyclopenta-2,4-dien-1-yl)ethane Derivatives as Potential Anti-ischemic Agents

Ischemic heart disease (IHD) remains a leading global health challenge, necessitating the development of safer and more effective anti-ischemic agents. This study investigates the therapeutic potential of hypothetical di(cyclopenta-2,4-dien-1-yl)ethane derivatives using in-silico modeling, toxicity predictions, and molecular docking studies. Fourteen derivatives (W1–W10, W8b, W9b, W8c and W9c) were designed and screened for bioavailability, toxicity, and docking affinities against key ischemia-related targets: Prostaglandin H Synthase 2 (PTGS2), Tumor Necrosis Factor (TNF), and Matrix Metalloproteinase 9 (MMP9). Compounds W8c and W9c emerged as promising candidates, exhibiting minimal predicted toxicity and favorable binding energies of -6.6 kcal/mol, -5.4 kcal/mol, and -7.9 kcal/mol, respectively, for PTGS2, TNF, and MMP9. These findings indicate their potential to inhibit inflammation, oxidative stress, and extracellular matrix degradation associated with myocardial ischemia. Structural modifications, including the introduction of alkyl groups, enhanced their therapeutic profiles. This work lays the foundation for the rational design of next-generation anti-ischemic agents with improved efficacy, safety, and bioavailability. Future research will focus on synthesizing and validating these derivatives in preclinical and clinical settings to address the challenges of IHD treatment.