Structures and Conformations of Metabolites of Antitumor Cyclic Hexapeptides, RA-VII and RA-X

• Published in: Chemical & pharmaceutical bulletin Vol. 40; no. 11; pp. 2984 - 2989
• Main Authors: ITOKAWA, Hideji, SAITOU, Keiko, YAMADA, Kenji, TAKEYA, Koichi, MORITA, Hiroshi
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 1992; 公益社団法人日本薬学会; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; antitumor activity; Bile - metabolism; Biological and medical sciences; biotransformation; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Chromatography, High Pressure Liquid; conformation analysis; cyclic hexapeptide; cytotoxic activity; General pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Male; Medical sciences; metabolite; Microsomes, Liver - metabolism; Molecular Conformation; Peptides, Cyclic - chemistry; Peptides, Cyclic - metabolism; Peptides, Cyclic - pharmacology; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; RA-VII; RA-X; Rabbits; Rats; Rats, Sprague-Dawley; Rubia cordifolia; Science & Technology; Structure-Activity Relationship; Tumor Cells, Cultured; Tyrosine - chemistry; CHEMOSENSITIVITY; SUZUKACILLIN; ASSAY; ANTITUMOR ACTIVITY; CYTOTOXIC ACTIVITY; DECAPEPTIDE; RA-VII; BIOTRANSFORMATION; RUBIAE RADIX; CONFORMATION ANALYSIS; RUBIA-CORDIFOLIA; RA-X; METABOLITE; CYCLIC HEXAPEPTIDE; Antineoplastic agent; Intravenous administration; Molecular structure; Digestive system; Metabolite; Pharmacognosy; Liver; Extract; Metabolism; In vitro; Hexapeptide; In vivo; Structure activity relation; Dicotyledones; Animal; Angiospermae; Rubiaceae; Plant origin; Spermatophyta; Pharmacokinetics; Bile; Conformation
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.40.2984

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.