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 Cot. In vitro assays with recombinant human PKC alpha 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 C alpha inhibitory activity. (c) 2006 Elsevier Ltd. All rights reserved.