Structure–activity relationship studies on an antitumor marine macrolide using aplyronine a–swinholide A hybrid. Issue 14 (24th March 2022)

• Record Type: Journal Article
• Authors: Ohyoshi, Takayuki; Takano, Atsuhiro; Kikuchi, Imari; Ogura, Tomotaka; Namiki, Mayu; Miyazaki, Yuto; Hirano, Takahiro; Konishi, Shota; Ebihara, Yuta; Takeno, Koichi; Hayakawa, Ichiro; Kigoshi, Hideo
• Is Part Of: Organic & biomolecular chemistry. Volume 20:Issue 14(2022)
• Page Start: 2922
• Page End: 2938
• Publication Date: 2022-03-24
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob00118g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Aplyronine A–swinholide A hybrid, a simplified analog of aplyronine A, was designed and synthesized for structure–activity relationship studies. Abstract : An aplyronine A–swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein–protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The importance of the methoxy group in the N, N, O -trimethylserine ester was clarified by the structure–activity relationship studies of the amino acid moiety by using the hybrid analogs. Furthermore, the comparison of the actin-depolymerizing activities between the side chain analogs of aplyronine A and swinholide A showed that the side chain analog of swinholide A had much weaker actin-depolymerizing activity than that of aplyronine A.