title: Chemistry of ecteinascidins. Part 3: preparation of 2'-N-acyl derivatives of ecteinascidin 770 and evaluation of cytotoxicity.
abstract: A three-step transformation of ecteinascidin 770 (1b) into 2'-N-indole-3-carbonyl derivative 3 via 18,6'-O-bisallyl-protected derivative 4a, which was shown to have higher cytotoxicity than 1b, is presented. In addition, a number of 2'-N amide derivatives of 1b have been prepared from 4a and their in vitro cytotoxicity were determined by measuring IC₅₀ values against human cell lines HCT116, QG56, and DU145. Benzoyl amide derivatives 7a-c showed similar in vitro cytotoxicity to 1b, whereas the nitrogen-containing heterocyclic derivatives 7d-h and cinnamoyl derivatives 9a-b showed higher cytotoxicity than 1b. In contrast, the 18,6'-O-bisallyl protected derivatives 4a-c, 6a-h, and 8a-b showed dramatic decreases in cytotoxicity relative to 1b.
authors.affiliation: Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Panithi
authors.initials: P
authors.lastname: Saktrakulkla
authors.forename: Satoru
authors.initials: S
authors.lastname: Toriumi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Chamnan
authors.initials: C
authors.lastname: Patarapanich
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014561:Urochordata / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C464992:ecteinascidin 770