Synthesis and Structure-Activity Relationships of Quaternary Coptisine Derivatives as Potential Anti-ulcerative Colitis Agents

Journal of Medicinal Chemistry
Zhi-Hui ZhangHai-Lin Qin

Abstract

Thirty quaternary coptisine derivatives from a synthesized library were found to activate the in vitro transcription of x-box-binding protein 1 (XBP1). Among these, the dihydrocoptisines were demonstrated by in vitro XBP1 transcriptional activity assays and animal experiments to be much more active anti-ulcerative colitis (UC) agents than quaternary coptisines, tetrahydrocoptisines, and the positive control. Unsubstituted dihydrocoptisine exhibited more significant anti-UC efficacy than dihydrocoptisines substituted at the C-8 or C-13 position. The EC50 value of dihydrocoptisine for XBP1 transcriptional activation was 2.25 nM. Dihydrocoptisine exhibited a significant dose-effect relationship, as indicated by biomarkers in in vitro and in vivo experiments. According to this study, the starting material's reductive states and the substitution patterns of the dihydrocoptisines were determined to be the critical parameters for modulating their anti-UC efficacy, and the dihydrocoptisine skeleton was designated as the key pharmacophore. The synthesized dihydrocoptisine is a promising lead for developing anti-UC drugs.

References

Jun 5, 2002·European Journal of Pharmacology·Ho H LukChi H Cho
Dec 27, 2005·Bioorganic & Medicinal Chemistry Letters·Marco FranceschinStephen Neidle
May 30, 2006·Bioorganic & Medicinal Chemistry Letters·Ki Duk ParkSung Uk Kim
Nov 18, 2006·Phytochemistry·Lenka GrycováRadek Marek
May 8, 2009·Bioorganic & Medicinal Chemistry·Siritron SamosornJohn B Bremner
Oct 12, 2010·Bioorganic & Medicinal Chemistry Letters·Ki Duk ParkSung Uk Kim
Jan 22, 2011·Gut·Teresa FritzArthur Kaser
Apr 17, 2013·Seminars in Immunopathology·Arthur KaserRichard S Blumberg
Mar 13, 2014·Toxicology Letters·Di YuQuansheng Zhou
Jul 17, 2014·Journal of Asian Natural Products Research·Zhi-Hui ZhangHai-Lin Qin
Sep 10, 2014·European Journal of Medicinal Chemistry·Zhi-Hui ZhangHai-Lin Qin

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Citations

Jan 17, 2017·The Journal of Organic Chemistry·Li-Rong WenMing Li
Jul 25, 2017·Journal of Natural Products·Qian LiHai-Lin Qin
Feb 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Ana Cristina Alves de AlmeidaAnderson Luiz-Ferreira
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bo WangHai-Lin Qin
Jan 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jieun ChooEunok Im
Feb 9, 2021·Organic Letters·Kai Liu, Xuefeng Jiang
Jun 17, 2021·Journal of Asian Natural Products Research·Xiang LiHai-Lin Qin

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