Exploring Benzo[d]thiazol-2-Amine Derivatives, Synthesis, and Molecular Docking Insights Potential Anticancer Agents Targeting HER Enzyme and DNA.

Abstract

The synthesis and characterization of benzo[d]thiazol-2-amine derivatives, which were prepared by reacting benzothiazole with para-aminobenzophenone in ethanol, supplemented with glacial acetic acid. Subsequently, compound (2) was synthesized from compound (1) using NaNO₂, H₃PO₄, and HNO₃ in a water-based solvent, resulting in 2-hydroxy-1-naphthaldehyde. Another derivative, compound (3), was synthesized by reacting compound (1) with vanillin under similar conditions. Structural characterization involved IR spectroscopy and melting point determination, while molecular properties were estimated to assess drug-like characteristics. The main point of this study is to synthesize and research drug-like characteristics, biological activities, and docking studies. Molecular docking studies (MDS) were conducted using AutoDock Vina to evaluate the binding affinity of compounds 1, 2, and 3 with the enzyme Human Epidermal growth factor receptor (HER). The docking simulations aimed to elucidate drug-DNA interactions, focusing on hydrogen bonding, hydrophobic interactions, and binding energies. The compounds' conformations were analyzed to identify their potential binding modes within the DNA groove. Compounds 2 and 3 exhibited higher binding affinities to the HER enzyme compared to compound 1, with compound 2 showing the highest affinity docking scores of - 10.4, - 9.9, and - 9.8 kcal/mol for the top three poses. These results suggest that compounds 2 and 3 could potentially interact more effectively with the enzyme and DNA, attributed to their structural features and interaction profiles. Synthesized and characterized benzo[d]thiazol-2-amine derivatives and evaluated their biological activities against gram-positive and gram-negative bacteria. The compounds demonstrated diverse biological activities, likely due to the various functional groups within their 4- to 5-ring structures. Molecular docking studies indicated that compounds 2 and 3 have promising potential as cancer therapy candidates, showing strong binding affinities to the HER enzyme and effective interactions with DNA.