Synthesis of norisoboldine derivatives and bioactivity assay for inducing the generation of regulatory T cells

• Published in: Bioorganic & medicinal chemistry letters Vol. 37; p. 127844
• Main Authors: Chang, Lan, Zhang, Qin, Tang, Yunqing, Fang, Yulai, Dou, Renjie, Chu, Yuyao, Xia, Yufeng, Wei, Zhifeng, Chen, Li, Dai, Yue
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.04.2021; Elsevier
• Subjects: Chemistry; Chemistry, Medicinal; Chemistry, Organic; Derivatives; Life Sciences & Biomedicine; Norisoboldine; Pharmacology & Pharmacy; Physical Sciences; Regulatory T cells; Science & Technology; Structural modification; Ulcerative colitis; Norisoboldine; Structural modification; Derivatives; Regulatory T cells; Ulcerative colitis; AUTOIMMUNE; ULCERATIVE-COLITIS; INDUCTION; LIGAND
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2021.127844

[Display omitted] In this study, we used chemical modification to improve the pharmacological activity of norisoboldine (NOR). A new NOR-benzoic acid derivative, named DC-01, showed more potent induction of Treg cell differentiation than NOR. The in vitro effective concentration of DC-01 (1 μM) is about an order of magnitude lower than that of NOR (10 μM). DC-01 (28, 56 mg/kg) showed better amelioration of dextran sodium sulfate-induced colitis in mice than NOR (20, 40 mg/kg), and DC-01 (28 mg/kg) increased the number of Treg cells slightly better than NOR (20 mg/kg). In summary, DC-01 exerts more potent induction of Treg cell generation, which might be a candidate drug for the treatment of inflammation- and immune-related diseases.