PHARMACOLOGICAL POTENTIAL OF 1,5-BENZOTHIAZEPINE DERIVATIVES: AN UPDATED REVIEW OF BIOLOGICAL ACTIVITIES, MOLECULAR TARGETS AND STRUCTURE–ACTIVITY RELATIONSHIPS

Abstract

1,5-Benzothiazepines represent an important class of heterocyclic compounds that have gained considerable attention in medicinal chemistry due to their broad spectrum of pharmacological activities. The unique fusion of benzene and thiazepine rings imparts remarkable biological versatility, making them valuable scaffolds in drug discovery. This review comprehensively highlights the chemistry, synthesis and diverse therapeutic potentials of 1,5-benzothiazepine derivatives with emphasis on their antimicrobial, anticonvulsant, anticancer, anti-inflammatory and antidiabetic properties. Various studies have demonstrated that structural modifications on the benzothiazepine nucleus, particularly the introduction of electron-withdrawing or hydrophilic substituents, significantly influence biological activity and selectivity. Halogenated and heteroaryl-substituted derivatives exhibit potent antimicrobial and antitubercular activity, while specific analogues show promising anticonvulsant efficacy through GABAergic modulation. Similarly, 1,5-benzothiazepines with tailored substitutions have revealed noteworthy cytotoxicity against several cancer cell lines and some derivatives demonstrate strong COX-2 inhibition and α-glucosidase inhibitory potential, indicating anti-inflammatory and antidiabetic relevance. The integration of in silico modeling, structure-activity relationship (SAR) analysis and green synthetic approaches has further advanced understanding of their pharmacological mechanisms. Collectively, these findings underline the importance of 1,5-benzothiazepine derivatives as versatile lead structures for the design of novel therapeutic agents.