Design, Synthesis, and Evaluation of a Novel Phenanthrene Derivative as a Potential DNA Intercalator

Novel DNA intercalators are crucial for developing new pharmacologically active agents, such as chemotherapeutics, and advanced probes for cell labeling and imaging. Herein, we report the design and two-step synthesis of a novel phenanthrene-based derivative bearing cytosine moieties (PHE-CYT-3,6-TFA), formulated as a trifluoroacetic acid salt to enhance water solubility. In silico docking confirmed a favorable binding score of -7.21, predicting intercalation stabilized by π-π stacking and hydrogen bonding. Experimental photophysical characterization confirmed strong DNA interaction, evidenced by a significant decrease in fluorescence quantum yield (from 12% to 5.4%), a spectral blue shift in emission, and changes in fluorescence decay time. The compound was comprehensively screened for in vitro antibacterial, antimycobacterial, antifungal, antiviral, and anticancer activities. Crucially, PHE-CYT-3,6-TFA demonstrated excellent biocompatibility, showing nontoxicity toward a noncancerous human cell line (IC₅₀ > 50 μM) and no hemolytic activity in an ex vivo assay.