New Selective Cytotoxic Diterpenylquinones and Diterpenylhydroquinones

• Published in: Journal of medicinal chemistry Vol. 44; no. 8; pp. 1257 - 1267
• Main Authors: Miguel del Corral, José Ma, Gordaliza, Marina, Castro, Ma Angeles, Mahiques, Ma Mar, Chamorro, Pablo, Molinari, Aurora, García-Grávalos, Ma Dolores, Broughton, Howard B, San Feliciano, Arturo
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 12-04-2001
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Diterpenes - chemical synthesis; Diterpenes - chemistry; Diterpenes - pharmacology; Drug Screening Assays, Antitumor; General aspects; Humans; Medical sciences; Mice; Models, Molecular; Pharmacology. Drug treatments; Quinones - chemical synthesis; Quinones - chemistry; Quinones - pharmacology; Structure-Activity Relationship; Tumor Cells, Cultured; Antineoplastic agent; Human; Terpenoid; Anthraquinone derivatives; Lung; Quinone; Rodentia; Benzoquinone derivatives; Melanoma; Diels Alder addition; Cytotoxicity; Naphthoquinone derivatives; Diphenols; In vitro; Vertebrata; Mammalia; Cell line; Structure activity relation; Mouse; Animal; Diterpene; Phenols; Colon; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm001048q

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.