Design, synthesis and pharmacological evaluation of new anticancer fused pentacycles.
The quinoline chromophore has long formed the basis for the clinical development of novel antitumour agents. Camptothecin derivatives have already proved their clinical efficacy and compounds such as ascididemin (pyridoacridine family), DHDMC (protoberberine family) have a very promising future. During our search for new cytotoxic molecules, we have designed compounds based on the benzo[c]pyrido[2,3,4-kl]acridine skeleton which combines the structural features of ascididemin and DHDMC. Corresponding compounds were synthesized and evaluated for their cytotoxic activity against human prostatic PC-3 cell lines. Some have shown promising biological activity in inhibiting the growth of cell lines which are resistant to camptothecin.
Chackal
Sarah
S
Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de Lille 2, BP 83, 59006 Lille, France.
Houssin
Raymond
R
Pommery
Nicole
N
Henichart
Jean-Pierre
JP
D000166:Acridines / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000473:pathology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000166:Acridines; D000970:Antineoplastic Agents; D011725:Pyridines