Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2

Journal Article · Tue Jun 19 00:00:00 EDT 2012 · J. Med. Chem.

DOI:https://doi.org/10.1021/jm201251c· OSTI ID:1039785

Reddy, P.V. Narasimha; Jensen, Katherine C; Mesecar, Andrew D; Fanwick, Phillip E; Cushman, Mark ^[1]

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1. Purdue

A variety of ammosamide B analogues have been synthesized and evaluated as inhibitors of quinone reductase 2 (QR2). The potencies of the resulting series of QR2 inhibitors range from 4.1 to 25,200 nM. The data provide insight into the structural parameters necessary for QR2 inhibitory activity. The natural product ammosamide B proved to be a potent QR2 inhibitor, and the potencies of the analogues generally decreased as their structures became more distinct from that of ammosamide B. Methylation of the 8-amino group of ammosamide B was an exception, resulting in an increase in quinone reductase 2 inhibitory activity from an IC{sub 50} of 61 nM to IC{sub 50} 4.1 nM.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: NIH
• OSTI ID: 1039785
• Journal Information: J. Med. Chem., Journal Name: J. Med. Chem. Journal Issue: (1) ; 02, 2012 Vol. 55; ISSN JMCMAR; ISSN 0022-2623
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
BENZOQUINONES
DESIGN
EVALUATION
METHYLATION
OXIDOREDUCTASES
QUINOLINES
SYNTHESIS