Structures and conformations of metabolites of antitumor cyclic hexapeptides, RA-VII and RA-X.
Metabolites of antitumor cyclic hexapeptides, RA-VII and -X which were isolated from Rubia cordifolia were studied by hepatic microsomal biotransformation in rats and in bile juice of rabbits to which these drugs were administered intravascularly. Their structures and conformations were elucidated by two-dimensional nuclear magnetic resonance techniques, temperature effect on NH protons and nuclear Overhauser effect experiments. Specific N-demethylation of Tyr-3, O-demethylation and hydroxylation at aromatic rings of Tyr-3 and -5 were observed. Compared with metabolites of RA-VII, most of RA-X was excreted unchanged in the bile juice. Relationship among their structures, conformations and antitumor activities is also discussed.
Itokawa
H
H
Department of Pharmacognosy, Tokyo College of Pharmacy, Japan.
Saitou
K
K
Morita
H
H
Takeya
K
K
Yamada
K
K
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C079025:RA X peptide; D014443:Tyrosine; C043548:RA VII