A simplified analog of debromoaplysiatoxin lacking the B-ring of spiroketal moiety retains protein kinase C-binding and antiproliferative activities. (1st November 2022)

• Record Type: Journal Article
• Authors: Sekido, Tomoki; Yamamoto, Kosuke; Yanagita, Ryo C.; Kawamani, Yasuhiro; Hanaki, Yusuke; Irie, Kazuhiro
• Is Part Of: Bioorganic & medicinal chemistry. Volume 73(2022)
• Publication Date: 2022-11-01
• Subjects: Aplysiatoxin -- Simplified analog -- Conformer -- Protein kinase C -- Isozyme selectivity -- Antiproliferative activity -- Molecular dynamics simulation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.116988
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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.