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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amides / chemical synthesis*
-
Amides / chemistry
-
Amides / pharmacology
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Crystallography, X-Ray
-
Drug Design
-
Drug Screening Assays, Antitumor
-
Heterocyclic Compounds, 3-Ring / chemical synthesis*
-
Heterocyclic Compounds, 3-Ring / chemistry
-
Heterocyclic Compounds, 3-Ring / pharmacology
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Pyrroles / chemical synthesis*
-
Pyrroles / chemistry
-
Pyrroles / pharmacology
-
Quinolines / chemical synthesis*
-
Quinolines / chemistry
-
Quinolines / pharmacology
-
Quinone Reductases / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Amides
-
Antineoplastic Agents
-
Heterocyclic Compounds, 3-Ring
-
Pyrroles
-
Quinolines
-
ammosamide B
-
NRH - quinone oxidoreductase2
-
Quinone Reductases