Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Table 1

Effects of metformin, phenformin, and metformin prodrugs on the human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE).

Compound	IC50 [μmol/mL]		SI
	AChE	BuChE	AChE	BuChE
Metformin	2.350 ± 0.122	>1000.000^×	>425.531^×	<0.002^×
Phenformin	4.940 ± 0.575	0.259 ± 0.031	0.052	19.073
Prodrug 1	0.890 ± 0.157	0.028 ± 0.002	0.031	31.786
Prodrug 2	>1000.000^×	0.184 ± 0.014	<1.84010^−4^×	>5434.000^×
Prodrug 3	1.190 ± 0.139	0.205 ± 0.029	0.172	5.805
Tacrine	(2.770 ± 1.11)10^−4	(9.080 ± 4.54)10^−5	3.278	0.305

The values are given as mean ± standard deviation (SD) in three independent experiments. Values of IC₅₀ for tacrine were published previously [41]. The above values for tacrine were calculated from units μg/mL (0.055 ± 0.022 and 0.018 ± 0.009, resp.). SI (selectivity index)—the AChE selectivity index is defined as IC₅₀ BChE/IC₅₀ AChE affinity ratio. Selectivity for BChE is defined as IC₅₀(AChE)/IC₅₀(BChE). ^×Theoretical values counted on the basis of extrapolated plots for metformin towards BuChE and prodrug 2 towards AChE. SI was calculated based on the theoretical IC₅₀ values.