REPOSITIONING OF SELECTED MEDICINAL AGENT - AN EXPLORATORY ATTEMPT IN SILICO-BASED APPROACH

Raghu S.*, Thaslima M., Vaagini K., Vadumal Dhanush Arjunan, Veeramanikandan D.K., Vignesh A.

Drug repositioning has emerged as a promising strategy in pharmaceutical research, offering a cost-effective and time-efficient alternative to traditional drug discovery. This study investigates the repositioning potential of Dantrolene, a muscle relaxant with an established pharmacological profile, against phosphodiesterase (PDE) isoforms (PDE1-PDE10) using molecular docking and In-Silico approaches. The ligand was retrieved from PubChem, optimised with the MMFF94 force field, and docked against cleaned PDE crystal structures obtained from the Protein Data Bank. Docking simulations were performed using AutoDock Vina, with binding affinity, hydrogen bonding, hydrophobic interactions, and RMSD values analysed to assess stability and specificity. The results revealed that Dantrolene exhibited the strongest binding affinity for PDE7 (-10.0 kcal/mol), accompanied by low RMSD values, indicating highly stable interactions. PDE3 (-9.4 kcal/mol) and PDE2 (-9.3 kcal/mol) also demonstrated favourable binding with stable conformations. PDE8 formed the highest number of hydrogen bonds but showed moderate affinity, while PDE6 displayed unstable docking despite reasonable binding energy. Overall, the findings suggest that Dantrolene may act as a potential PDE inhibitor, particularly targeting PDE7. This computational study highlights the utility of drug repositioning strategies and provides a foundation for further in vitro and in vivo validation to explore novel therapeutic applications of Dantrolene.