Synthesis and in vitro evaluation of quaternary ammonium derivatives of chlorambucil and melphalan, anticancer drugs designed for the chemotherapy of chondrosarcoma.
To enhance affinity for malignant cartilaginous tumors (chondrosarcomas), quaternary ammonium (QA) conjugates of chlorambucil and melphalan were prepared by linking the QA moiety to nitrogen mustards via an amide bond. They exhibited closely similar and sometimes more favorable values than their parent compounds. In the cell lines tested, the two QA conjugates displayed appreciable cytotoxicity, the QA conjugate of chlorambucil even showing an enhanced efficiency against chondrosarcoma compared with chlorambucil.
Giraud
Isabelle
I
INSERM Unité 484, Rue Montalembert, BP 184, 63005 Clermont-Ferrand Cedex, France.
Rapp
Maryse
M
Maurizis
Jean-Claude
JC
Madelmont
Jean-Claude
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002699:Chlorambucil / Q000737:chemistry* / Q000494:pharmacology; D002813:Chondrosarcoma; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma; D008558:Melphalan / Q000737:chemistry*; D051379:Mice; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D000644:Quaternary Ammonium Compounds; D002699:Chlorambucil; D008558:Melphalan