Synthesis, cytotoxic activity, and DNA binding properties of antitumor cis-1,2-dihydroxy-1,2-dihydrobenzo[b]acronycine cinnamoyl esters.

Abstract

Monocinnamoyl esters at position 2 of (+/-)-cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one and their acetyl derivatives at position 1 were prepared as stabilized analogues of the anticancer alkylating agent S23906-1. Monocinnamoyl esters at position 2 were slower DNA alkylators than the reference 2-monoacetate. Mixed esters bearing an acetyl ester group at position 1 and a cinnamoyl ester group at position 2 alkylated DNA slower than S23906-1. A strong correlation was observed between cytotoxicity and DNA alkylation kinetics, with slower alkylators displaying more potent antiproliferative activities. The most cytotoxic compounds proved to be significantly active in vivo against murine C-38 adenocarcinoma implanted in mice, but less potent than S23906-1.

• Authors: Quyên Do, Wen Tian, Rodrigue Yougnia, Thomas Gaslonde, Bruno Pfeiffer, Alain Pierré, Stéphane Léonce, Laurence Kraus-Berthier, Marie-Hélène David-Cordonnier, Sabine Depauw, Amélie Lansiaux, Romain Mazinghien, Michel Koch, François Tillequin, Sylvie Michel, Hanh Dufat
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 5 Pg. 1918-27 (Mar 01 2009) ISSN: 1464-3391 [Electronic] England
• PMID: 19217791 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• S 23906-1
• DNA
• Acronine

Topics

• Acronine (analogs & derivatives, chemical synthesis, chemistry, pharmacology, toxicity)
• Animals
• Antineoplastic Agents, Alkylating (chemical synthesis, chemistry, toxicity)
• Cell Line, Tumor
• DNA (chemistry)
• Kinetics
• Mice
• Mice, Inbred C57BL
• Transplantation, Homologous