Structural Modification, Bio Activity Of Derivatives Of Three Protopines And Their Stucture-activity Relationship

Protopine compounds are a class of natural alkaloids with extensive biological activities.They are used in clinical widely, such as antibacterial and antivirus, anti-platelet aggregation,sedation and analgesia, hypotensive and antiarrhythmic, but little research on the agricultureand veterinary drugs. On the basis of, protopine, cryptopine and allocryptopine are chosen asparent compounds to modify. Moreover, the antifungal experiment and the acaricidal activityanalysis was preliminary investigated, and the structure-activity relationship (SAR) of thethree compounds was elaborated. The research contents and results are as follows:1. A series of substituted analogues of the three alkaloids have been synthesized,protopine have five derivatives, cryptopine have four derivatives and allocryptopine have sixderivatives. The structures of the compounds were well characterized by1H NMR,13C NMR,ESI-MS and melting point. Four compounds (P-1, A-1, A-7, C-1) were recrystallized by slowevaporation and their single-crystal structures were determined by X-ray crystallography.2. Fusarium graminearum, Valsa mali, Alternaria brassicae, Alternaria alternata, BlastFungus, Alternario solani, Cotton Fusarium Wilt, Fusarium bulbigenum, Fusariumoxysporium and Clanerela cinyulate were used as the tested phytopathogenic fungi. Theantifungal activity of the compounds was tested by growth rate method. The result showedthat the compounds have antifungal activity at a certain extent at the concentration of100μg/mL against the most pathogenic fungi. Several the compounds can promote individualpathogens’ growth.3. The acaricidal activity of the compounds was tested at the concentration of5.0mg/mL. The psoroptes (P. cuniculi) isolated from rabbits was used to evaluate the acaricidalactivity of target molecules. The result showed that among three parent compounds protopineis the most active one and followed by cryptopine. Dihydroprotopine is the most active one.4. The quantitative structure-activity relationships of the three compounds showed thatthe-OCH2O-can improve the activity and the carbonyl is not the active group.These results provided some theoretical basis for further knowing about the modificationand structure-acaricidal activity of the protopine, cryptopine and allocryptopine.