Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents.
Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Zhi-Hui
ZH
Zhang
b Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
Jing
J
Li
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Hai-Jing
HJ
Zhang
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
An-Jun
AJ
Deng
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Lian-Qiu
LQ
Wu
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Zhi-Hong
ZH
Li
b Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
Hong-Rui
HR
Song
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Wen-Jie
WJ
Wang
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China.
Hai-Lin
HL
Qin
D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D039321:Hydrastis / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D000071701:Regulatory Factor X Transcription Factors / Q000378:metabolism; D012492:Salts
C000613526:8-acetonyldihydrocoptisine; D000071701:Regulatory Factor X Transcription Factors; D012492:Salts; C034384:coptisine; D001599:Berberine; C039639:dihydroberberine
(±)-8-acetonyldihydroberberine-type intermediate; Quaternary berberine-type alkaloid organic acid salts; XBP1-activating activity; dihydroberberine-type intermediate; liposolubility; synthesis