Synthesis and cytotoxic activities of usnic acid derivatives.
Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and in the PTS deficient CHO-MG cells. In addition, alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor known to indirectly enhance the activity of the PTS and consequently increase the cytotoxicity of cytotoxic drugs entering cells via the PTS, had no effect on the activity of the polyamine derivatives. The more active derivative (1,8-diaminooctane derivative) displayed similar activities on all cancer cell lines studied and induced apoptosis.
EA 4090 Substances lichéniques et photoprotection, UFR des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes Cedex, France.
Marc-Antoine
MA
Bazin
Anne-Cécile
AC
Le Lamer
Jean-Guy
JG
Delcros
Isabelle
I
Rouaud
Philippe
P
Uriac
Joël
J
Boustie
Jean-Charles
JC
Corbel
Sophie
S
Tomasi
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D011073:Polyamines; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001572:Benzofurans; D002352:Carrier Proteins; D011073:Polyamines; C073339:usnic acid