1. Structure-activity relationship studies on an antitumor marine macrolide using aplyronine a-swinholide A hybrid.
- Author
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Ohyoshi T, Takano A, Kikuchi I, Ogura T, Namiki M, Miyazaki Y, Hirano T, Konishi S, Ebihara Y, Takeno K, Hayakawa I, and Kigoshi H
- Subjects
- Actins drug effects, HeLa Cells, Humans, Marine Toxins, Structure-Activity Relationship, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Macrolides chemistry, Macrolides pharmacology
- 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.
- Published
- 2022
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