Cytotoxic Activity of Distinct Families of Phosphonic Acid Derivatives – A Chemocentric Approach to Assess Their Molecular Action

Abstract Phosphorus containing small molecules (particularly α‐aminophosphonates, α‐hydroxyphosphonates and bisphosphonates) represent a unique chemical space among the biologically active compounds. We selected 35 diverse compounds that showed remarkable cytotoxicity effects on various cancer cell lines. However, the exact mechanism of action often requires further investigations, in vitro or in silico target identification even though many target‐based activity data were gathered for the above cluster of compounds. In our conceptual account, we offer a systematic in silico analysis between the cytotoxicity, cell lines, their (over)expressed protein targets associated with malignant diseases, and the activity data on protein targets already reported for those compounds in the hope that we gain better understanding and explanation, what is behind their cytotoxic behavior.