Fig. 1
Characterization of the effects of seven biguanides on mitochondrial respiration. a Differences in molecular structure between phenformin and proguanil and the five test compounds (all compounds shown in the neutral form). b Biguanide IC50 values for inhibition of NADH:decylubiquinone oxidoreduction by isolated bovine heart complex I (white), and NADH:O2 oxidoreduction by bovine heart (light gray) and mouse heart (dark gray) mitochondrial membranes. The data from three or four technical replicates were fit using Prism, and presented as best-fit IC50 values with 95 % confidence intervals. c Inhibition of succinate:O2 oxidoreduction in bovine mitochondrial membranes by biguanides at concentrations equivalent to the IC50 values for NADH:O2 oxidoreduction. Data are mean values ± standard error of the mean (SEM) (n = 3); *p ≤ 0.05. d Correlation between the IC50 values for isolated bovine complex I and the octanol:PBS partition coefficients (log10 P values) of the biguanides. Compounds that inhibit cellular and mitochondrial respiration strongly (see main text) are shown with open symbols and gray text, and those that do not with closed symbols and black text. The dagger (†) indicates values reported previously [4]. Data for log10 P are mean values ± SEM (n = 3). Individual data points for panels b, c, and d are provided in Additional file 1. phenf. phenformin, prog. proguanil