A Review on Benzothiazole Scaffolds as Potential Antidepressant Agents: Synthesis, Behavioral, and Mechanistic Evaluation

ABSTRACT Benzothiazoles are a class of heterocycles that have significant utility in modern therapeutic chemistry. It is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives possessing antidepressant activity along with their structure‐activity relationship (SAR) of the last three decades (1994–2025), shedding light on the molecular features that enhance their antidepressant efficacy. As depression is the most prevalent mental health disorder globally, the key objective of this review is to explore strong efficacy of the benzothiazoles in treating depression owing to their pharmacological impact on the central nervous system (CNS) and the significant ability to interact with serotonin transporters, 5‐HT 1A and 5‐HT 2A along with the inhibition of monoamine oxidase (MAO) enzyme crucial in managing depression. By providing a comprehensive analysis of these compounds, the study aims to pave the way for the development of novel benzothiazole‐based drugs for treating depression, offering significant potential toward future therapeutic advancements.