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

Abstract

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.

Authors:
; ; ; ;  [1]
  1. (Purdue)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1039785
Resource Type:
Journal Article
Journal Name:
J. Med. Chem.
Additional Journal Information:
Journal Volume: 55; Journal Issue: (1) ; 02, 2012; Journal ID: ISSN 0022-2623
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; BENZOQUINONES; DESIGN; EVALUATION; METHYLATION; OXIDOREDUCTASES; QUINOLINES; SYNTHESIS

Citation Formats

Reddy, P.V. Narasimha, Jensen, Katherine C., Mesecar, Andrew D., Fanwick, Phillip E., and Cushman, Mark. Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2. United States: N. p., 2012. Web. doi:10.1021/jm201251c.
Reddy, P.V. Narasimha, Jensen, Katherine C., Mesecar, Andrew D., Fanwick, Phillip E., & Cushman, Mark. Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2. United States. doi:10.1021/jm201251c.
Reddy, P.V. Narasimha, Jensen, Katherine C., Mesecar, Andrew D., Fanwick, Phillip E., and Cushman, Mark. Tue . "Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2". United States. doi:10.1021/jm201251c.
@article{osti_1039785,
title = {Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2},
author = {Reddy, P.V. Narasimha and Jensen, Katherine C. and Mesecar, Andrew D. and Fanwick, Phillip E. and Cushman, Mark},
abstractNote = {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.},
doi = {10.1021/jm201251c},
journal = {J. Med. Chem.},
issn = {0022-2623},
number = (1) ; 02, 2012,
volume = 55,
place = {United States},
year = {2012},
month = {6}
}