Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:31

Article

Basiri, Alireza^1,3  Zhang, Wenting^1,3  Garrison, Jered^1,2,3,4 

[1] Univ Nebraska Med Ctr, Coll Pharm, Dept Pharmaceut Sci, 985830 Nebraska Med Ctr, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA

[3] Univ Nebraska Med Ctr, Ctr Drug Delivery & Nanomed, 985830 Nebraska Med Ctr, Omaha, NE 68198 USA

[4] Univ Nebraska Med Ctr, Eppley Canc Ctr, 985950 Nebraska Med Ctr, Omaha, NE 68198 USA

关键词: DNBM;    Prodrug;    Prostate cancer;    Hypoxia;   

DOI  :  10.1016/j.bmcl.2020.127697

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free