3G5M

Synthesis of Casimiroin and Optimization of Its Quinone Reductase 2 and Aromatase Inhibitory activity

Summary for 3G5M

• Entry DOI: 10.2210/pdb3g5m/pdb
• Descriptor: Ribosyldihydronicotinamide dehydrogenase [quinone], ZINC ION, 6-methoxy-9-methyl[1,3]dioxolo[4,5-h]quinolin-8(9H)-one, ... (5 entities in total)
• Functional Keywords: casimiroin, qr2, nq02, cytoplasm, fad, flavoprotein, metal-binding, oxidoreductase, phosphoprotein, polymorphism, zinc
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P16083
• Total number of polymer chains: 2
• Total formula weight: 54595.86

Authors

Maiti, A.,Sturdy, M.,Marler, L.,Pegan, S.D.,Mesecar, A.D.,Pezzuto, J.M.,Cushman, M. (deposition date: 2009-02-05, release date: 2009-03-24, Last modification date: 2023-09-06)

Primary citation

Maiti, A.,Reddy, P.V.,Sturdy, M.,Marler, L.,Pegan, S.D.,Mesecar, A.D.,Pezzuto, J.M.,Cushman, M.
Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities.
J.Med.Chem., 52:1873-1884, 2009

PubMed Abstract: An efficient method has been developed to synthesize casimiroin (1), a component of the edible fruit of Casimiroa edulis, on a multigram scale in good overall yield. The route was versatile enough to provide an array of compound 1 analogues that were evaluated as QR2 and aromatase inhibitors. In addition, X-ray crystallography studies of QR2 in complex with compound 1 and one of its more potent analogues has provided insight into the mechanism of action of this new series of QR2 inhibitors. The initial biological investigations suggest that compound 1 and its analogues merit further investigation as potential chemopreventive or chemotherapeutic agents.

PubMed: 19265439
DOI: 10.1021/jm801335z

Experimental method

X-RAY DIFFRACTION (1.84 Å)