Molecular Docking Study of Benzothiazole Derivatives for Anti-Alzheimer's Activity on Human BACE-1 Complex AYH- 011 Target

Abstract

Benzothiazole derivatives have become a topic of interest in modern pharmacology due to their various pharmacological actions, such as their ability to fight cancer, bacteria, fungi, and HIV. This study investigated the potential of five benzothiazole derivatives with distinct functional groups as anti-Alzheimer's compounds. All derivatives, except Thiazoloquinazolinedione and ethionamide, have a pyrimidine ring in addition to the benzothiazole moiety. The study used molecular docking techniques to evaluate the binding affinity of these derivatives to the protein complex 3K5F - Human Bace-1, which is associated with Alzheimer's disease pathology. Thiazoloquinazolinedione had the highest docking score (-6.8) comparing the ligand AYH (-7.0) upon redocking. Specific interaction points were identified within chains A and B of the protein complex, indicating promising ligand-receptor interactions. The study highlights the significance of benzothiazole derivatives in Alzheimer's research, citing previous reports of their potential to reduce β-amyloid plaques, a hallmark of the disease. As SWISS-ADME predictions indicate, these compounds have weak base properties, unique methine centres in the thiazole ring, favourable blood-brain barrier penetration, and reduced toxicity. Further pharmacological, structure-activity relationship (SAR), and synthetic studies are necessary to elucidate their therapeutic usefulness and confirm their effectiveness in fighting Alzheimer's disease, thereby advancing the search for life-saving treatments in medicinal chemistry.

Keywords

Docking, Benzothiazole, Heterocyclic, Alzheimer's