Chemistry of ecteinascidins. Part 2. Preparation of 6'-O-acyl derivatives of stable ecteinascidin and evaluation of cytotoxicity.
A large amount of stable ecteinascidin 770 (1b) was isolated from the Thai tunicate, Ecteinascidia thurstoni, which was pretreated with potassium cyanide in buffer solution (pH 7), along with a minor metabolite, ecteinascidin 786 (1c). A number of 6'-O-acyl derivatives 3-19 and three diacetyl derivatives 2a-c of the stable 1b were prepared and evaluated for activity against human tumor cell lines HCT116, QG56, and DU145. Nitrogen-containing heterocyclic ester derivatives such as 12, 13, and 16-19 showed similar in vitro cytotoxicity to 1b, whereas the other derivatives were less cytotoxic than 1b. Furthermore, we discovered that the N-indole-3-carbonyl derivative of ecteinascidin 770 (22) has higher cytotoxicity than 1b.
Puthongking
Ploenthip
P
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University; Pathumwan, Bangkok 10330, Thailand.
Patarapanich
Chamnan
C
Amnuoypol
Surattana
S
Suwanborirux
Khanit
K
Kubo
Akinori
A
Saito
Naoki
N
D000215:Acylation; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004952:Esters / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines; D015394:Molecular Structure; D014561:Urochordata / Q000737:chemistry
D000970:Antineoplastic Agents; D004952:Esters; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C464992:ecteinascidin 770