Phosphonothioamidate in Bleomycin-Induced Pulmonary Fibrosis in Rats: Experimental Anti-Fibrotic Assessment, Theoretical DFT Calculations and Molecular Docking Study

A novel Phosphonothioamidate derivative (EThmP) was designed, chemically synthesized, characterized and evaluated for its ability to inhibit oxidative stress and fibrotic process. In the present investigation, (EThmP) was used on an experimental murine model of pulmonary fibrosis induced by bleomycin (BLM). Wistar rats were given a single dose of BLM (4 mg/kg, intratracheal), while (EThmP) (10 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks. Our results indicate a significant decrease of superoxide dismutase activity and an increase in lipid peroxidation after BLM treatment compared to control group, while (EThmP) (10 mg/kg) was able to normalize the level of these oxidative markers, decreased collagen accumulation and lung damage compared to BLM group. Computational chemistry was carried out on the studied compound by using DFT and PM6 basis set. Calculations were employed to get more insights in the stability, the bioactivity prediction and the structure–activity relationship using energies and molecular orbitals (MO). Furthermore, the molecular docking approach was used to model the interaction between the (EThmP) and the selected collagen peptides (ID: 1CAG, 1QSU, 1Q7D, 3A1H, 1NQD and 1V4F) against anti-fibrotic disease.