Stimuli-responsive benzothiazole-phenothiazine derivatives: mechanochromism, AIE, acid sensing, and anticancer efficacy in benzo[a]pyrene-induced cancer models†

Abstract

Mechanofluorochromic (MFC) materials are emerging as a versatile candidate for optoelectronic and biomedical applications. In the present work, we designed and synthesized four MFC materials, namely BT-PTZ-1, BT-PTZ-2, BT-PTZO-1, and BT-PTZO-2, using Suzuki cross-coupling reaction. These materials possess benzothiazole (BT) as an acceptor moiety and different donors, including phenothiazine (PTZ) and triphenylamine (TPA), with variations in their spacer units. The photophysical properties of these derivatives have been explored, revealing solvatochromism, aggregation-induced emission (AIE), acid sensing, and mechanochromic behaviour. Single crystal X-ray analysis of BT-PTZO-2 provides crucial structural insights, revealing the twisted conformation of the TPA donor and the bent structure of the PTZ oxide spacer. The biological studies of these BT derivatives reveal the therapeutic potential against benzo[a]pyrene (B[a]P)-induced carcinogenesis in A549 (lung) and HEK293 (kidney) cells. Treatment with BT-PTZ-2 reflects anti-cancerous properties, with significant up-regulation of p53 and down-regulation of β-catenin and pNF-κB. Additionally, downregulation of mitochondrial fission protein (DRP1) and oxidative stress through DCFDA staining in lung cells are observed with BT-PTZ-2 treatment. These findings strongly suggest that BT-PTZ-2 can inhibit lung cancer cell proliferation and survival, suggesting it to be a promising anti-cancer agent. This comprehensive study of these MFC materials provides insights into their design, synthesis, and properties, in addition to their potential applications in various optoelectronic and biomedical fields.