Abstract
In order to design new antitumor drugs and study the relationship between antitumor and anti-oxidative activity of spin-labeled derivatives of podophyllotoxin, five novel pyrroline spin-labeled 4beta-N-substituted-amino acid-4'-O-demethylepipodophyllotoxin compounds (11a-e) (Scheme 2) were synthesized and evaluated. Their cytotoxicity against three tumor cell lines (human lung carcinoma A-549, human leukemia cell HL-60 and multiple myeloma RPMI-8226) has been evaluated using a MTT-based assay in vitro. Also, we determined malondialdehyde (MDA) in liver and kidney homogenate of SD rats by the TBA method. The five new compounds showed either superior or comparable inhibitory activity against A-549, HL-60 and RPMI-8226 cell lines compared with etoposide (VP-16, 2), and all the tested compounds showed more significant antioxidant activities than VP-16. Furthermore, the partition coefficients were measured and preliminary structure-activity relationships are presented.
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