Cytostatic hetero-fused 7-deazapurine nucleosides, pharmacology, metabolism and mechanism of action

Recently we discovered that hetero-fused 7-deazapurine nucleosides exert nanomolar cytostatic activity, but their biological target and mechanism of action are unknown. Therefore, we propose to synthesize other analogues and derivatives, systematically study structure-activity relationship, intracellular metabolism, identify the cellular target(s) and the mode of action of these compounds, as well as their pharmacological properties (ADME), toxicity and in vivo activity, in order to optimize the lead structures and select candidates for preclinical development toward antitumor drugs.