Synthesis, X-Ray, Hirshfeld Surface, DFT, and Molecular Docking Investigation of N-(5H-Dibenzo[a,d][7]Annulen-5-Ylidene)-2-Methylpropane-2-Sulfinamide

• Published in: Polycyclic aromatic compounds Vol. 44; no. 9; pp. 5914 - 5926
• Main Authors: Chelouan, Ahmed, Herrera, Alberto, Dorta, Romano, Filali, Insaf, Anouar, El Hassane
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 20.10.2024; Taylor & Francis Ltd
• Subjects: Addictions; ADMET; Antidepressants; Anxiety disorders; Binding sites; Carbonic anhydrase; Carbonic anhydrase I; Chemical synthesis; Chronic pain; DFT; dibenzo[ad]cycloheptene; Ketones; Magnetic resonance spectroscopy; Mental depression; Molecular docking; NMR spectroscopy; Parameter identification; Pharmacokinetics; Physicochemical properties; Structural analysis; tert-Butanesulfinyl ketimines; Toxicity; Tricyclic antidepressants
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2023.2270643

Dibenzocycloheptene antidepressants are tricyclic antidepressants (TCAs) that contain the dibenzocycloheptene moiety in their chemical structures. They are used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Herein, we report the synthesis of a pure tricyclic antidepressant containing dibenzocycloheptene moiety named N-(5H-dibenzo[a,d][7]annulen-5-ylidene)-2-methylpropane-2-sulfinamide (3) in high chemical yield through condensing (R)-tert-butanesulfinamide with a dibenzosuberon ketone. Its structure is elucidated by employing the X-ray technique, NMR spectroscopy characterization, and DFT calculations at the B3LYP/6-31++G(d,p) level of theory. The geometrical parameters are relatively well reproduced, and the optimized and X-ray geometries are relatively well superimposed. The interconnects in the crystalline form of 3 were identified through the analysis of its Hirshfeld surface (HS) and fingerprint plots. The highest interatomic contacts were found between H ... H of 58.2% and C.H of 30.6%. Further, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) pharmacokinetics, and physicochemical properties of 3 were determined, which showed that 3 may act as a carbonic Anhydrase I inhibitor. The binding affinity of 3 into the binding site of carbonic Anhydrase I is investigated using a molecular docking study. It forms a stable complex into the binding site of CA I with a binding energy of −7.12 kcal/mol.