This paper reported the synthesis, structure-activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a
mange mite, of 25
ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, (1)H- and (13)C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 µg/mL, respectively, which were 2.1- to 8.3-fold the activity of
ivermectin (LC50=247.4 µg/mL), a standard
drug in the treatment of Psoroptes cuniculi. Compared with
ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 µmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the
benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-
Cinnamates were more effective than their (Z)-isomer. Nevertheless, the
carbon-
carbon double bond in the acrylic
ester moiety was proven not to be essential to improve the activity of
cinnamic acid esters. Thus, the results strongly indicate that
cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel
acaricides for the effective control of animal or human
acariasis.