Structural Modification of Sanguinarine and Chelerythrine and Their in vitro Acaricidal Activity against Psoroptes cuniculi

Abstract

Sanguinarine (1) and chelerythrine (2) are two quaternary benzo[c]phenanthridine alkaloids (QBAs). Eighteen derivatives of 1 and 2 were synthesized by modification of C=N⁺ bond and evaluated for their in vitro acaricidal activity against Psoroptes cuniculi, a mange mite. A new method was developed to prepare 6-alkoxy dihydro derivatives of 1 and 2 (1a-e; 2a-e). Among all the compounds, only 6-alkoxy dihydrosanguinarines (1a-e) showed significant acaricidal activity at 5.0 mg/mL and 1a possessed the strongest activity (LC₅₀ = 339.70 ± 0.75 mg/L, LT₅₀ = 6.53±0.04 h), comparable with a standard drug ivermectin (LC₅₀ = 168.19±11.79 mg/L, LT₅₀ = 16.54±0.11 h). The iminium moiety in 1 and 2 was proven to be the determinant for their acaricidal properties. 6-Alkoxy dihydro derivatives (1a-e, 2a-e) were prodrugs of 1 and 2. Compared with 7,8-dimethoxy groups, 7,8-methylenedioxy group was able to significantly improve the bioactivity. The present results suggested that QBAs are promising candidates or lead compounds for the development of new isoquinoline acaricidal agents.