Computational design, synthesis and biological evaluation of para-quinone-based inhibitors for redox regulation of the dual-specificity phosphatase Cdc25B.
Quinoid inhibitors of Cdc25B were designed based on the Linear Combination of Atomic Potentials (LCAP) methodology. In contrast to a published hypothesis, the biological activities and hydrogen peroxide generation in reducing media of three synthetic models did not correlate with the quinone half-wave potential, E(1/2).
Keinan
Shahar
S
Department of Chemistry, Duke University, Durham, NC, USA.
Paquette
William D
WD
Skoko
John J
JJ
Beratan
David N
DN
Yang
Weitao
W
Shinde
Sunita
S
Johnston
Paul A
PA
Lazo
John S
JS
Wipf
Peter
P
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D011809:Quinones; D006861:Hydrogen Peroxide; D020687:cdc25 Phosphatases