New selective cytotoxic diterpenylquinones and diterpenylhydroquinones.
A new series of diterpenylquinone/hydroquinones has been prepared by Diels-Alder cycloaddition between three labdanic diterpenoids (myrceocommunic acid, methyl myrceocommunate, and myrceocommunyl acetate) and p-benzoquinone or 1,4-naphthoquinone. Influences of the quinone/hydroquinone fragment and other structural features, such as the different functionalities in the terpenic core, are considered in relation to the cytotoxicity toward neoplastic cells and the selectivity of these diterpenylnaphthoquinones/hydroquinones and anthraquinones. Several compounds showed IC50 values under the micromolar level, and four of these derivatives were evaluated at the NCI screening panel. The results showed an important selectivity toward renal cancer lines, identifying these compounds as a very promising group of antineoplastics.
Miguel Del Corral
J M
JM
Departamento de Química Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, E-37007-Salamanca, Spain. jmmcs@gugu.usal.es
Gordaliza
M
M
Castro
M A
MA
Mahiques
M M
MM
Chamorro
P
P
Molinari
A
A
García-Grávalos
M D
MD
Broughton
H B
HB
San Feliciano
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004224:Diterpenes; D011809:Quinones