3UXH

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

Summary for 3UXH

• Entry DOI: 10.2210/pdb3uxh/pdb
• Related: 3UXE
• Descriptor: Ribosyldihydronicotinamide dehydrogenase [quinone], ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: quinone reductase, cytosol, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P16083
• Total number of polymer chains: 2
• Total formula weight: 53983.98

Authors

Cushman, M.,Mesecar, A.D.,Fanwick, P.E.,Narasimha, R.,Jensen, K.C. (deposition date: 2011-12-05, release date: 2012-01-18, Last modification date: 2024-05-22)

Primary citation

Reddy, P.V.,Jensen, K.C.,Mesecar, A.D.,Fanwick, P.E.,Cushman, M.
Design, synthesis, and biological evaluation of potent quinoline and pyrroloquinoline ammosamide analogues as inhibitors of quinone reductase 2.
J.Med.Chem., 55:367-377, 2012

PubMed 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.

PubMed: 22206487
DOI: 10.1021/jm201251c

Experimental method

X-RAY DIFFRACTION (1.53 Å)