Preparation and Biological Activity of Amino Acid and Peptide Conjugates of Antitumor Hydroxymethylacylfulvene

• Published in: Journal of medicinal chemistry Vol. 43; no. 19; pp. 3577 - 3580
• Main Authors: McMorris, Trevor C, Yu, Jian, Ngo, Huan-Tony, Wang, Haixia, Kelner, Michael J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.09.2000; Amer Chemical Soc
• Subjects: Amino Acids - chemistry; Animals; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Chemistry, Medicinal; Drug Screening Assays, Antitumor; General aspects; Inhibitory Concentration 50; Life Sciences & Biomedicine; Medical sciences; Peptides - chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rats; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Tumor Cells, Cultured; METABOLISM; EFFICACY; RAT; MGI-114; TRADITIONAL ANTICANCER AGENTS; ACYLFULVENE; ILLUDINS; MODEL; HMAF; Antineoplastic agent; Lung; Ketol; Combinatorial chemistry; Cytotoxicity; Spiran; Cell line; Structure activity relation; Tetrapeptide; Sulfur peptide; Peptide synthesis; Chemical synthesis; Tumor cell
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0000315

The primary hydroxyl group in hydroxymethylacylfulvene, a potent antitumor drug, is readily replaced by thiols including cysteine, N-acetylcysteine, homocysteine, and glutathione. Best yields are obtained when reaction is carried out in the presence of dilute sulfuric acid. A variety of sulfur-containing analogues have been prepared, and their toxicity to tumor cells was examined.