Structures of cytotoxic bicyclic hexapeptides, RA-XIX, -XX, -XXI, and -XXII, from Rubia cordifolia L.
Graphical abstract
Introduction
RA-VII (1)1, 2 and bouvardin (NSC 259968, 2)3 are tumor cell growth inhibitors isolated from the plants, Rubia cordifolia L. (Rubiaceae) and Bouvardia ternifolia (Cav.) Schltdl. (Rubiaceae), respectively. Their structures are characterized by the presence of a 14-membered strained ring, an unusual cycloisodityrosine unit, formed by an ether linkage between the two aromatic rings of Tyr-5 and Tyr-6. Their antitumor action is considered to be due to inhibition of protein synthesis through interaction with eukaryotic ribosomes.4, 5 Recently, RA-VII (1) was shown to cause conformational changes in F-actin and stabilization of actin filaments to induce G2 arrest.6 In our further studies on the cyclopeptide constituents in the roots of R. cordifolia, four new RA-series peptides, RA-XIX (3), -XX (4), -XXI (5), and -XXII (6), were isolated. This paper describes their isolation, structure determination, and cytotoxicity against P-388 cells.
Section snippets
Results and discussion
A methanol extract obtained from dried roots of R. cordifolia (50 kg) was partitioned between chloroform and water. The chloroform-soluble portion was subjected to a series of column chromatography using silica gel, alumina, and then aminopropyl-bonded silica gel eluting with a series of chloroform/methanol mixtures to give a fraction rich in RAs. The residue of this fraction, obtained after removal of the solvent, was crystallized from methanol to give crystals of crude RAs, which, after
General
Melting points were determined on a Yanaco MP-3 apparatus and are recorded uncorrected. Optical rotations were measured on a JASCO P-1030 digital polarimeter, IR spectra on a JASCO FT/IR 620 spectrophotometer, and UV spectra on a JASCO V-530 spectrophotometer. NMR spectra were measured on a Bruker DRX-500 spectrometer at 300 K. The 1H chemical shifts in CDCl3 or CD3OD were referenced to the residual CHCl3 (7.26 ppm) or CD2HOD (3.31 ppm), and the 13C chemical shifts were referenced to the solvent
References and notes (14)
- et al.
- et al.
FEBS Lett.
(1982) - et al.
Bioorg. Chem.
(1995) - et al.
Cancer Lett.
(2004) - et al.
Tetrahedron
(1991) - et al.
Tetrahedron
(1991) - et al.
Chem. Pharm. Bull.
(1983)
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