Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we have reported the design and synthesis of a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug. Specifically, we explored the impact of various leaving groups and the introduction of a carboxylic acid group on the biological performance of the DNBM constructs. Once in hand, the Log D values, cytotoxicity in PC-3 and DU-145 human prostate cancer cells lines and the hypoxia selectivities of the DNBM analogs were examined. Overall, the DNBM constructs were found to be tolerant to modifications with none of the explored modifications substantially degrading the cytotoxic potential of the constructs.

Automated summary

In this study, a series of dinitrobenzamide mustards (DNBM) based on the PR-104A hypoxia-selective prodrug were designed and synthesized. Various leaving groups and the introduction of a carboxylic acid group were explored to investigate the biological performance of the DNBM constructs. The results showed that the DNBM constructs were tolerant to modifications without substantially degrading their cytotoxic potential.