Synthesis and cytotoxic evaluation of C-9 oxidized podophyllotoxin derivatives.
A series of podophyllotoxin and podophyllic aldehyde derivatives, lacking the lactone ring and oxidized at C-9 position, has been prepared. The functionalities considered at C-9 were carboxylic acids and several derivatives such as esters, amides, nitriles or anhydrides. The synthesized compounds were cytotoxic at the micromolar level, though less potent and selective than the parent compounds, revealing the influence of the C-9 electrophilic character on the potency and selectivity of these cyclolignans.
Castro
Ma Angeles
MA
Departamento de Química Farmacéutica, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain. macg@usal.es
Miguel del Corral
José M
JM
Gordaliza
Marina
M
García
Pablo A
PA
Gómez-Zurita
Ma Antonia
MA
San Feliciano
Arturo
A
D000447:Aldehydes; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011034:Podophyllotoxin