Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

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Abstract

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.

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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