A simplified analog of debromoaplysiatoxin lacking the B-ring of spiroketal moiety retains protein kinase C-binding and antiproliferative activities

[Display omitted] A simplified analog (3) of aplysiatoxin was synthesized. Compound 3 has only one tetrahydropyran ring at positions 3–7, the A-ring of the spiroketal moiety, which is the conformation-controlling unit for the macrolactone ring. Nuclear magnetic resonance (NMR) analysis and density f...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2022-11, Vol.73, p.116988-116988, Article 116988
Main Authors: Sekido, Tomoki, Yamamoto, Kosuke, Yanagita, Ryo C., Kawamani, Yasuhiro, Hanaki, Yusuke, Irie, Kazuhiro
Format: Article
Language:English
Subjects:
Antiproliferative activity
Aplysiatoxin
Conformer
Isozyme selectivity
Molecular dynamics simulation
Protein kinase C
Simplified analog
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Summary:[Display omitted] A simplified analog (3) of aplysiatoxin was synthesized. Compound 3 has only one tetrahydropyran ring at positions 3–7, the A-ring of the spiroketal moiety, which is the conformation-controlling unit for the macrolactone ring. Nuclear magnetic resonance (NMR) analysis and density functional theory (DFT) calculations indicated that 3 existed as an equilibrium mixture of two conformers arising from inversion of the chair conformation of the 2,6-trans-tetrahydropyran ring. The des-B-ring analog 3 binds protein kinase C isozymes and exhibits antiproliferative activity toward human cancer cell lines, comparable to 18-deoxy-aplog-1 with a spiroketal moiety.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2022.116988