Behavioral and histopathological insights into phenylthiazolyl-1,3,5-triazines: Potential antidepressant candidates in a rat model of depression

Objectives: To evaluate the antidepressant-like effects of Phenylthiazolyl-1,3,5-triazine derivatives through behavioral tests, molecular docking, and histopathological analysis in a rat brain model of depression. Methods: Phenylthiazolyl-1,3,5-triazine derivatives were synthesized and administered at a dose of 30 mg/kg in albino rats. Behavioral effects were assessed using the Forced Swim Test and Tail Suspension Test. Molecular docking with MD simulations via CDocker was employed to analyze ligand-receptor interactions. Histological analysis of brain tissues was conducted to assess structural and vascular changes. Results: Among the derivatives, PS1 and PS5 showed significant antidepressant-like activity compared to standard imipramine. Molecular docking revealed that hydrogen bonding, pi-pi interactions, and intermolecular neighbor effects stabilized the ligand-receptor complexes. Histopathological analysis of PS1-treated rats demonstrated preserved vascular integrity, reduced edema, and the absence of hydrophobic alterations. Conclusions: Phenylthiazolyl-1,3,5-triazines, particularly PS1, exhibit promising potential as antidepressant agents. Their behavioral efficacy and protective histological effects suggest therapeutic relevance. Further studies integrating biomarkers and gene expression analyses are needed to optimize these derivatives for clinical application.