title: Synthesis and biological activity of analogues of diazaquinomycin A, a new thymidylate synthase inhibitor.
abstract: Diazaquinomycin A (1), a new thymidylate (TMP) synthase inhibitor, is poorly soluble in various solvents and exhibits no antitumor activity, while a series of the analogues prepared from 1 are more soluble in water and chloroform than 1, and some of them exhibit antitumor activity in mice. Some analogues in which the lactam rings are replaced by pyridine rings did not inhibit TMP synthase. The diethoxy analogue 25 is a 10-fold more potent inhibitor of TMP synthase than 1. The diacetoxy analogue 23 exhibits significant antitumor activity (T/C: 175%) against Meth-A fibrosarcoma in mice.
authors.affiliation: Kitasato Institute, Kitasato University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuzuki
authors.forename: T
authors.initials: T
authors.lastname: Yokozuka
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002286:Carcinoma, Ehrlich Tumor; D055598:Chemical Phenomena; D002621:Chemistry; D005354:Fibrosarcoma / Q000188:drug therapy; D005493:Folic Acid Antagonists; D006367:HeLa Cells / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D011809:Quinones / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D013291:Streptococcus / Q000187:drug effects; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D005493:Folic Acid Antagonists; D011809:Quinones; C046688:diazaquinomycin A; D013940:Thymidylate Synthase