Molecular Docking of Benzimidazole Derivatives as Potential Serotonin Transporter (SERT) Inhibitors in Depression Disease

ABSTRACT Depression, which is a serious and complicated central system mental disorder, and characterized by a pervasive and sustained depressed mood, low interest, cognitive impairment, low motivation, and even suicidal tendencies. This research focuses on the chemical preparation of a series of benzimidazole derivatives. In the first step, 2‐hydrazinobenzimidazole K1 and 2‐hydrazino‐5‐nitrobenzimidazole K2 were prepared by reacting aqueous hydrazine with 2‐mercaptobenzimidazole and 2‐mercapto‐5‐nitrobenzimidazole, respectively. Subsequently, K2 was reacted with benzoyl chloride to yield the amide derivative K3 . In a further step, Schiff base K4 was prepared by reacting K1 with p‐bromobenzaldehyde. Subsequently, K5 , an oxazolidin‐5‐one derivative, was prepared by reacting K4 with trichloroacetic acid. The chemical structures of the synthesized compounds were confirmed using various techniques, including FTIR and 1 H‐NMR. To evaluate benzimidazole and its two derivatives as potential of serotonin transporter (SERT) protein (6DZW) inhibitors through in silico analysis. Molecular docking studies revealed that the effectiveness of compounds ( K3 and K5 ) was comparable with that of Paroxetine, an FDA‐approved antidepressant drug against the SERT protein, responsible for many side effects. The interaction of the K5 compound with protein 6DZW causes the most negative binding energy (‐7.048 kcal/mol) with residues Tyr176, while the calculated value for the Paroxetine compound was (−7.594 kcal/mol). The compound K3 shows a good binding energy for the selected protein (−6.776 kcal/mol) with residues (Glu493). Molecular docking of these compounds may therefore be recommended as new anti‐depressant agents to contrast the SERT protein.