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

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2011 Dec 31

PMID 22206487

Citations 10

Authors

P V Narasimha Reddy

Katherine C Jensen

Andrew D Mesecar

Phillip E Fanwick

Mark Cushman

Affiliations

Soon will be listed here.

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(50) of 61 nM to IC(50) 4.1 nM.

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