Preparation and antitumor activity of [N-alkyl-Ala2]RA-VII, antitumor cyclic hexapeptide

Bioorganic & Medicinal Chemistry Letters
1994.0

Abstract

A number of [N-alky-Al@A-VII derivatives have been prepared from RA-VII (1) and evaluated for in vitro antitumor activity against P388 and KB cells, and partly for in vivo anti-P388 activity. All analogues retained significant cytotoxicity, and N-prenyl derivative (2j) showed more promising in vivo activity than 1. RAs, antitumor cyclic hexapeptides, have been isolated from Japanese and Chinese medicinal plants of the genuses Rubic ukune and R cordifilia (Rubiaceae), and particular interest has centered on the unique bicyclic structure and antitumor activity of them? RA-VII (l), the most potent congener of RAs is now under clinical trial in Japan as an anticancer agent. 3 1 is potentially promising anticancer agent, but its rather high toxicity restricted the doses and schedule for administration.3 To find a lower toxic alternative, we have undertaken chemical modification of 1. Derivation of 1 has been difficult thus far due to the lack of a suitable functional structure, and only 0-acylation or O-alkylation of the phenolic hydroxyl group of RA-V (Ty#de-&nethylRA-VII) has been extensively studied.4 Another possible part for modifications seemed to be the amide nitrogen of Ak?, at which a methyl group could be introduced by excess amount of methyl iodide and KF-alumina? Recently we found that under the phase transfer conditions the amide nitrogen is effectively alkylated withN, Ndialkylaminoethyl chloride without any racemixation of the constituting amino acid residues6 By using various alkylating agent, this method is found to be applicable to prepare the corresponding N-alkylated dexhtives. In this report we will describe the preparation and biological evaluation of a number of ~-all+Ala2m-VU derivatives.

Knowledge Graph

Similar Paper

Preparation and antitumor activity of [N-alkyl-Ala2]RA-VII, antitumor cyclic hexapeptide
Bioorganic & Medicinal Chemistry Letters 1994.0
Per-N-methylated analogues of an antitumor bicyclic hexapeptide RA-VII
Bioorganic & Medicinal Chemistry 2011.0
Studies on antitumor cyclic hexapeptides RA obtained from Rubiae Radix, Rubiaceae. VI Minor antitumor constituents.
Chemical and Pharmaceutical Bulletin 1986.0
Isolation and antitumor activity of cyclic hexapeptides isolated from Rubiae radix.
Chemical and Pharmaceutical Bulletin 1984.0
Design and synthesis of a bis(cycloisodityrosine) analogue of RA-VII, an antitumor bicyclic hexapeptide
Bioorganic & Medicinal Chemistry Letters 2008.0
Isolation, structural elucidation, and synthesis of RA-XVII, a novel bicyclic hexapeptide from Rubia cordifolia, and the effect of side chain at residue 1 upon the conformation and cytotoxic activity
Tetrahedron Letters 2004.0
Aza-cycloisodityrosine analogue of RA-VII, an antitumor bicyclic hexapeptide
Bioorganic & Medicinal Chemistry Letters 2013.0
New antitumor bicyclic hexapeptides, RA-XI, -XII, -XIII and -XIV from Rubia cordifolia.
Chemical and Pharmaceutical Bulletin 1992.0
A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: Structure, semi-synthesis, and cytotoxicity
Bioorganic & Medicinal Chemistry Letters 2008.0
A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: Structure, semi-synthesis, and cytotoxicity
Bioorganic & Medicinal Chemistry Letters 2008.0