title: Cryptopleurine analogs with modification of e ring exhibit different mechanism to rac-cryptopleurine and tylophorine.
abstract: 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-κB, AP-1, and CRE signaling pathways. Functional cryptopleurine analogs showed potent inhibition of NF-κB 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.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui-Chyn
authors.initials: HC
authors.lastname: Wong
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gullen
authors.forename: Wing
authors.initials: W
authors.lastname: Lam
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D007212:Indolizines / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000470:Alkaloids; D017362:Cyclic AMP Response Element-Binding Protein; D007212:Indolizines; D016328:NF-kappa B; D010616:Phenanthrenes; D018808:Transcription Factor AP-1; C007160:cryptopleurine; C004218:tylophorine