Novel carbamate derivatives of 4-beta-amino-4'-O-demethyl-4-desoxypodophyllotoxin as inhibitors of topoisomerase II: synthesis and biological evaluation.
A novel series of carbamate derivatives of 4-beta-amino-4'-O-demethyl-4-desoxypodophyllotoxin were synthesized. Their effect on human DNA topoisomerase II and antiproliferative activity was evaluated. Compounds 4a-c, 4g, 4j and 4k are topoisomerase II poisons that induce double-stranded breaks in DNA and exhibit increased cytotoxicity compared to etoposide.
Duca
Maria
M
UMR 176 CNRS, Institut Curie, Section de Recherche, 26 rue d'Ulm, 75248 Paris cedex 05, France.
Arimondo
Paola B
PB
Léonce
Stéphane
S
Pierré
Alain
A
Pfeiffer
Bruno
B
Monneret
Claude
C
Dauzonne
Daniel
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D002219:Carbamates; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004247:DNA; D011034:Podophyllotoxin