In recent years, buspirone has been co-administered with sertraline to resolve sexual disorders causedby sertraline. Therefore, the present study was conducted to investigate the interaction effect of twoantidepressants and anxiolytic drugs, sertraline and buspirone, on human serum albumin (HSA) usingspectroscopic and molecular docking techniques. Fluorescence emission spectroscopy and moleculardocking were used to calculate the binding affinity and determine the best binding sites for these twodrugs. Additionally, UV-visible and circular dichroism spectroscopy were performed to investigate theeffect of these drugs on the conformational changes of HSA. The results showed that both drugs havea strong ability to quench the fluorescence of HSA through a static mechanism, and cause structuralchanges in HSA. It was also found that binding of sertraline and buspirone to HSA is spontaneous(ΔG° <) and hydrophobic interactions, van der Waals forces and hydrogen bonds play a significantrole in these interactions in the ternary system. In addition, molecular docking data showed thatboth drugs bind with high affinity to the Trp residue in subdomain IIA. The binding constants (Kb) for(HSA-SRH)-BSH and (HSA-BSH)-SRH were equal to 6.30 and 3.99, respectively, at 298 K. This studydemonstrates that the presence of the second drug (buspirone/sertraline) affects the interaction andbinding affinity of the first drug (sertraline/buspirone) to human serum albumin.
