Inhibition of protein kinase C by dequalinium analogues: structure-activity studies on head group variations.
New dequalinium analogues and related heteroaromatic systems were synthesized and evaluated for inhibition of protein kinase Calpha. In vitro assays with recombinant human PKCalpha showed that the number of the aromatic ring head groups as well as their electron-richness, are critical factors that determine potency. The inhibitory strengths of the synthesized compounds are shown to correlate well with Mulliken charges on the head group ring nitrogen atoms making it possible to design likely candidate molecules having improved protein kinase Calpha inhibitory activity.
Abeywickrama
Chandima
C
Department of Chemistry, The Graduate Center, The City University of New York, New York, NY 10016-4309, USA.
Rotenberg
Susan A
SA
Baker
Arthur David
AD
D003868:Dequalinium / Q000031:analogs & derivatives* / Q000494:pharmacology; D015195:Drug Design; D004583:Electrons; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D006841:Hydrocarbons, Aromatic; D011994:Recombinant Proteins; D003868:Dequalinium; D051571:Protein Kinase C-alpha