Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

Alireza Basiri, Wenting Zhang, Jered Garrison

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number127697
JournalBioorganic and Medicinal Chemistry Letters
Volume31
DOIs
StatePublished - Jan 1 2021

Keywords

  • DNBM
  • Hypoxia
  • Prodrug
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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