Synthesis and biological evaluation of quinocarcin derivatives: thioalkyl-substituted quinones and hydroquinones

• Published in: Journal of medicinal chemistry Vol. 34; no. 7; pp. 1959 - 1966
• Main Authors: Saito, Hiromitsu, Hirata, Tadashi, Kasai, Masaji, Fujimoto, Kazuhisa, Ashizawa, Tadashi, Morimoto, Makoto, Sato, Akira
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.07.1991
• Subjects: Animals; Antibiotics, Antineoplastic - chemical synthesis; Antibiotics, Antineoplastic - therapeutic use; Benzoquinones - chemical synthesis; Benzoquinones - therapeutic use; Chemical Phenomena; Chemistry; Drug Screening Assays, Antitumor; Exact sciences and technology; HeLa Cells; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Humans; Leukemia P388 - drug therapy; Mice; Mice, Inbred BALB C; Organic chemistry; Oxazoles - chemical synthesis; Oxazoles - therapeutic use; Preparations and properties; Sarcoma 180 - drug therapy; Structure-Activity Relationship; Antineoplastic agent; Angular nitrogen heterocycle; Quinone; Polycyclic compound; Aromatic compound; Diphenols; Biological activity; Organic sulfide
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00111a006

Varieties of thioalkyl-containing quinone and hydroquinone analogues of quinocarcin (1a) were prepared effectively, by addition of mercaptan to 3a-c, which were derived from 1a via DX-52-1 (1b). Antitumor activities of these analogues were preliminarily evaluated by growth inhibition of HeLa S3 cells (in vitro) and increased life span of P388 implanted mice (in vivo). Bis(alkylthio)quinones 4a-d and 5a-d, and corresponding hydroquinones 9b-d exhibited high activities both in vitro and in vivo. They were superior to 1a especially in single administration. Selected compounds 4a, 4d, 5a, 5d, and 9b were subjected to further evaluation, and bis(methylthio)quinone 5a was revealed to possess broad-spectrum activity toward human xenographted carcinomas MX-1, Co-3, St-4, and LC-06.