title: Synthesis of 2,3-diaziridinyl-1,4-naphthoquinone sulfonate derivatives as potential antineoplastic agents.
abstract: A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulfonate series, at their optimum daily dosage level of 25 mg/kg X 6, produced 100%, 90%, 75%, 80%, and 100% 50-day survivors, respectively, of L1210 tumor-bearing mice. At a lower optimum daily dosage level of 20 mg/kg X 6, treatments with p-fluorobenzenesulfonate 11 and p-nitrobenzenesulfonate 15 resulted in 100% and 80% 50-day survivors. In the aliphatic sulfonate series, methanesulfonate 21 produced 80% 50-day survivors at a 10 mg/kg daily dosage level X 6. Benzenesulfonate 4, p-fluorobenzenesulfonate 11, 8-quinolinesulfonate 17, and 2-thiophenesulfonate 20 derivatives were also tested in mice bearing the B16 melanoma; these agents gave T/C X 100 values of 180, 182, 219, and 161, respectively, in this neoplastic cell system. Structure-activity relationships of compounds of this class are discussed.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: T S
authors.initials: TS
authors.lastname: Lin
authors.forename: S P
authors.initials: SP
authors.lastname: Xu
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhu
authors.forename: L A
authors.initials: LA
authors.lastname: Cosby
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001388:Aziridines / Q000138:chemical synthesis* / Q000494:pharmacology; D001389:Azirines / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D009285:Naphthoquinones