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Cryptopleurine Analogs with Modification of E Ring Exhibit Different Mechanism to Rac-Cryptopleurine and Tylophorine
Published: Monday, December 10, 2012
Author: Ying Wang et al.

by Ying Wang, Hui-Chyn Wong, Elizabeth A. Gullen, Wing Lam, Xiaoming Yang, Qian Shi, Kuo-Hsiung Lee, Yung-Chi Cheng

Tylophorine analogs exhibit a broad range of pharmacological activities, including anti-cancer, anti-inflammatory, anti-autoimmune, and anti-virus effects. Structure-activity relationship study of different structure tylophorine analogs can provide further understanding of their biological activity. Modifications on the E ring of the quinolizidine moiety of cryptopleurine analogs changed the potency and the selective inhibitory effect on NF-?B, AP-1, and CRE signaling pathways. Functional cryptopleurine analogs showed potent inhibition of NF-?B signaling pathway in both HepG2 and HEK-293 cell lines. The E ring structure analogs also differed in suppression of protein translation, and expression of cyclin D1. Our results showed that DCB-3503 or Rac-cryptopleurine could be a scaffold for modification to yield compounds with different mechanisms of action.
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