Author(s)

Zulfiqar Ahmad, Prasanna K. Dadi, Jesse Elord, Ismail O. Kady

Department of Biological and Environmental Sciences, Alabama A&M University, Normal, USA.
Department of Chemistry, East Tennessee State University, Johnson City, USA.

A series of structurally related diphenol aldimines (DPAs) were synthesized. These aldimines involve different substitution patterns of their phenolic groups, for the purpose of optimizing their ability to inhibit ATP synthase. The inhibitory effects of these DPA compounds were evaluated using purified F₁ and membrane-bound F₁F₀ E. coli ATP synthase. Structure-activity relationship studies of these di-phenol compounds showed that maximum inhibition was achieved when both phenolic groups are either in the meta-positions (DPA-7, IC₅₀ = 2.0 μM), or in the ortho-positions (DPA-9, IC₅₀ = 5.0 μM). The lowest ATP synthase inhibition was found to be when the phenolic groups are both in the para-positions (DPA-2, IC₅₀ = 100.0 μM). Results also show that the inhibitory effects of these compounds on ATPase are completely reversible. Identical inhibition patterns of both the purified F₁ and the membrane bound F₁F₀ enzyme were observed. Study of E. coli cell growth showed that these diphenol aldimines effectively inhibit both ATP synthesis and cell growth.

Aldimine; ATPase; ATP Synthase; Diphenol; Polyphenol; Enzyme Inhibition; E. coli

Ahmad, Z. , Dadi, P. , Elord, J. and Kady, I. (2012) Synthesis and evaluation of diphenol aldimines as inhibitors of Escherichia coli ATPase and cell growth. Advances in Biological Chemistry, 2, 160-166. doi: 10.4236/abc.2012.22019.