Synthesis, lipophilicity study and in vitro evaluation of some rodenticides as acetylcholinesterase reversible inhibitors

Figures & data

Table I.  Log P value for (Me₂N)P(O)(O–C₆H₅)₂ by the shake-flask method.

n-octanol/buffer (v/v)	C1	Ā(n=3)	C2	log P
1:2	3.48 × 10^− 2	0.276	2.7 × 10^− 3	1.037
1:4	3.48 × 10^− 2	0.245	2.4 × 10^− 3	1.035
1:6	3.48 × 10^− 2	0.214	2.1 × 10^− 3	1.010

Overall mean log P value ± SD: 1.027 ± 0.015

C₁ – concentration of stock solution in n-octanol before partitioning (mol L^–1); Ā –absorbance in buffer solution after partitioning (λ = 272 nm); C₂ – concentration of sample in buffer solution after partitioning (mol L^–1); log P – logarithm of the partition coefficient

Figure 1 Inhibition graph for target rodenticides.

Table II.  PASS output for N,N-Dimethyl phosphoramidic acid di,phenyl ester.

Biological activity	pa
CYP2A6 human substrate	0.824
Acetylcholinesterase inhibit	0.816
Dynein ATPase inhibitor	0.796
GTP diphosphokinase inhibitor	0.786
CYP2 substrate	0.777
Granzyme B inhibitor	0.731
Cholinergic	0.725
Carboxylesterase inhibitor	0.709

Table III.  Physicochemical properties and anti-AChE activity experimental and predictive values for target rodenticides.

X	Δ	π	logP	miLogP	IC50(mm)	pa(anti-AChE)
H	1.6	0	1.027	1.95	31.3	0.816
CH3	2.153	0.56	1.63	2.53	35.4	0.722
Cl	1.676	0.71	2.75	3.14	40.9	0.718