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[Syntheses and Structure-Activity Relationship Studies of Antitumor Bicyclic Hexapeptide RA-VII Analogues].
- Source :
-
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan [Yakugaku Zasshi] 2024; Vol. 144 (5), pp. 553-565. - Publication Year :
- 2024
-
Abstract
- A series of antitumor bicyclic hexapeptide RA-VII analogues modified at residue 2, 3, or 6 were prepared by the chemical transformation of the hydroxy, methoxy, or carboxy groups or the aromatic rings of natural peptides RA-II, III, V, VII, and X. Analogues with modified side chains or peptide backbones, which cannot be prepared by the chemical transformation of their natural peptides, and newly isolated peptides from Rubia cordifolia roots were synthesized by using protected cycloisodityrosines prepared by the degradation of bis(thioamide) obtained from RA-VII or the diphenyl ether formation of boronodipeptide under the modified Chan-Lam coupling reaction conditions. Studies of the conformational features of the analogues and the newly isolated peptides and their relationships with cytotoxic activities against the HCT-116, HL-60, KATO-III, KB, L1210, MCF-7, and P-388 cell lines revealed the following: the methoxy group at residue 3 is essential for the potent cytotoxic activity; the methyl group at Ala-2 and Ala-4 but not at D-Ala-1 is required to establish the bioactive conformation; the N-methyl group at Tyr-5 is necessary for the peptides to adopt the active conformation preferentially; and the orientation of Tyr-5 and/or Tyr-6 phenyl rings has a significant effect on the cytotoxic activity.
- Subjects :
- Humans
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents, Phytogenic pharmacology
Cell Line, Tumor
Oligopeptides chemistry
Oligopeptides pharmacology
Oligopeptides chemical synthesis
Plant Roots chemistry
Protein Conformation
Rubia chemistry
Structure-Activity Relationship
Peptides, Cyclic chemistry
Peptides, Cyclic pharmacology
Peptides, Cyclic chemical synthesis
Subjects
Details
- Language :
- Japanese
- ISSN :
- 1347-5231
- Volume :
- 144
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
- Publication Type :
- Academic Journal
- Accession number :
- 38692932
- Full Text :
- https://doi.org/10.1248/yakushi.23-00208