DESIGN AND SYNTHESIS OF DIBENZAZEPINE-BASED DISRUPTORS OF THE PERINUCLEOLAR COMPARTMENT

Metastasis remains the leading cause of cancer-related mortality, and effective strategies to suppress metastatic progression are limited. The perinucleolar compartment (PNC) has emerged as a promising target for anti-metastatic therapy, as it is predominantly observed in cancer cells and its prevalence correlates with disease progression and poor patient outcomes. Using the PNC as a phenotypic marker, a high-throughput screening campaign identified nine hit compounds. Among these, a dibenzazepine urea derivative reduced PNC prevalence in a metastatic cell line by approximately 30%. This work focuses on the design and synthesis of dibenzazepine-based analogues to improve PNC disruption. Prior efforts produced a library of twenty-nine compounds through systematic chemical optimization. In this study, fifteen additional analogues were synthesized using established synthetic routes. Ongoing work aims to expand this series with thiourea analogues and further optimize synthetic methodologies to support structure–activity relationship studies.