Design, synthesis and biological evaluation and anticancer agent of new dipyrrolo-diazaborinine-phenothiazine derivatives

Mitochondria have emerged as a promising therapeutic target in oncology due to their central regulatory roles in cellular homeostasis and apoptotic pathways. Herein, we present a rationally designed mitochondrial-targeting agent, phenolic thiazide -BODIPY (PBD), engineered through strategic conjugation of a BODIPY-pyridinium fluorophore with a phenolic thiazide pharmacophore. This novel theranostic platform demonstrates excellent ΔΨm-driven mitochondrial targeting, real-time fluorescence imaging ability (highly overlapping), and significant antitumor selectivity (cell-specific cytotoxicity with a >15-fold selectivity). Mechanistic investigations revealed that PBD exerts its antitumor effects through mitochondrial membrane potential collapse and subsequent superoxide burst, ultimately triggering apoptosis. This multimodal strategy establishes a new paradigm for image-guided precision therapy in mitochondrial dysfunction-related malignancies.