title: 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 (50% lethal concentrations (LC(50))=339.70±0.75 mg/L, 50% lethal time (LT(50))=6.53±0.04 h), comparable with a standard drug ivermectin (LC(50)=168.19±11.79 mg/L, LT(50)=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.
authors.affiliation: College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Miao
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Yang
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Song
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
mesh_terms: D056810:Acaricides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D053119:Benzophenanthridines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D040042:Psoroptidae / Q000187:drug effects*
chemical_list: D056810:Acaricides; D053119:Benzophenanthridines; D007546:Isoquinolines; C005705:sanguinarine; C016299:chelerythrine