Structural necessity of indole C5-O-substitution of seco-duocarmycin analogs for their cytotoxic activity.
A series of racemic indole C5-O-substituted seco-cyclopropylindole (seco-CI) compounds 1-5 were prepared by coupling in the presence of EDCI of 1-(tert-butyloxycarbonyl)-3-(chloromethyl)indoline (seg-A) with 5-hydroxy-, 5-O-methylsulfonyl, 5-O-aminosulfonyl, 5-O-(N,N-dimethylaminosulfonyl)- and 5-O-benzyl-1H-indole-2-carboxylic acid as seg-B. Compounds 1-5 were tested for cytotoxic activity against four human cancer cell lines (COLO 205, SK-MEL-2, A549, and JEG-3) using a MTT assay. Compounds 2 and 3 with small sized sulfonyl substituents like 5-O-methylsulfonyl and 5-O-aminosulfonyl exhibit a similar level of activity as doxorubicin against all cell lines tested.
College of Pharmacy, Catholic University of Daegu, Hayang, 712-702, Korea.
Taeyoung
T
Choi
Eunsook
E
Ma
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007211:Indoles