Exploring the therapeutic potential of phenothiazine derivatives in medicinal chemistry

Abstract

The phenothiazine analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on phenothiazine-containing compounds. In this study, we report synthesis techniques including heterogeneous catalyst-assisted, microwave-assisted, ultrasound-assisted, and combinatorial synthesis, as well as synthesis using the cyclization method, transition metal-catalyzed synthesis, and nanoparticle-mediated synthesis, which have enhanced the diversity and potential applications of phenothiazine compounds. The unique phenothiazine scaffold also exhibits an impressive potential as antifungal, anticancer, antiprotozoal and antioxidant therapies. Notably, phenothiazines demonstrate efficacy against various cancer cell lines and microbial pathogens which offers their therapeutic significance in managing complex diseases such as schizophrenia, cancer, and infectious diseases beyond their role in modulating neurotransmitter pathways. We also examine the structure–activity relationships, revealing how modifications to the phenothiazine core influence pharmacological efficacy and specificity. This review examines the state of the art in medicinal chemistry as it relates to the comprehensive and general summary of the different phenothiazine analogs, their use as starting building blocks of multifarious architectures on scales sufficient to drive human drug trials. The number of reports describing phenothiazine-containing highly active compounds leads to the expectation that this scaffold will further emerge as a potential candidate in the field of drug discovery. © 2024 The Author(s)