Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo[2,1-c][1,4]benzodiazepines related to anthramycin.
A new 7,8-methylenedioxy analogue (4) of (+)-porothramycin B (2) and its water-soluble sodium bisulfite derivative (15) have been synthesized in high yields and have been shown to exhibit high cytotoxic activities against several tumor cell lines. The new pyrrolo[2,1-c][1,4]benzodiazepine 4 was as effective against the resistant cell lines as against the doxorubicin-sensitive cell lines tested.
Langlois
N
N
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette, France. nicole.langlois@icsn.cnrs-gif.fr
Rojas-Rousseau
A
A
Gaspard
C
C
Werner
G H
GH
Darro
F
F
Kiss
R
R
D000876:Anthramycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C438952:(11R,11aS)-2-(N,N-dimethyl)acrylamide-1,10,11,11a-tetrahydro-11-methoxy-7,8-methylenedioxy-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one; D000970:Antineoplastic Agents; D000876:Anthramycin; D004317:Doxorubicin