Synthesis and cytotoxic activity of novel derivatives of 4'-demethylepipodophyllotoxin.
Nine novel 4beta-N-substituted-5-FU-4'-demethylepipodophyllotoxin derivatives were synthesized and evaluated as potential antitumor agents. All of the target compounds showed more significant cytotoxic activity against HL-60 and A-549 in vitro than VP-16 and 5-FU. Among them, 4beta-N-substituted-phenylalanine 5-Fu pentyl ester-4'-demethylepipodophyllotoxin (9 g) was found to exhibit most potent cytotoxic activity against HL-60 and A-549 cell (IC50 is 0.04 and <0.01 microM, respectively).
Chen
Shi-Wu
SW
State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.
Tian
Xuan
X
Tu
Yong-Qiang
YQ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005047:Etoposide; D011034:Podophyllotoxin; D005472:Fluorouracil; C072088:4'-demethylepipodophyllotoxin