Exerting DNA Damaging Effects of the Ilimaquinones through the Active Hydroquinone Species

• Main Authors: Apisada Jiso, Laphatrada Yurasakpong, Sirorat Janta, Kulathida Chaithirayanon, Anuchit Plubrukarn
• Format: Article
• Language: English
• Published: Österreichische Apotheker-Verlagsgesellschaft m. b. H. 2021-06-01
• Series: Scientia Pharmaceutica
• Subjects: sesquiterpene quinones; cytotoxicity; redox cycling; marine natural products
• Online Access: https://www.mdpi.com/2218-0532/89/2/26
• ISSN: 0036-8709; 2218-0532

Possessing the quinone moiety, ilimaquinone (<b>1</b>), a sponge–derived sesquiterpene quinone, has been hypothesised to express its cytotoxicity through a redox cycling process, yielding active product(s) that can cause DNA damage. To determine the DNA damaging effects of <b>1</b> and examine whether a redox transformation may participate in its functions, the DNA damaging properties of <b>1</b>, the corresponding hydroquinone (<b>2</b>) and hydroquinone triacetates (<b>3</b>) and their 5-epimeric counterparts (<b>4</b>–<b>6</b>) were tested and compared. When incubated directly with plasmid DNA, the hydroquinones were the only active species capable of cleaving the DNA. In cell-based assays, however, the quinones and hydroquinone triacetates were active in the same range as that of the corresponding hydroquinones, and all damaged the cellular DNA in a similar manner. The in situ reduction of <b>1</b> and <b>4</b> were supported by the decreases in the cytotoxicity when cells were pre-exposed to dicoumarol, an NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitor. The results confirmed the DNA damaging activities of the ilimaquinones <b>1</b> and <b>4</b>, and indicated the necessity to undergo an in-situ transformation into the active hydroquinones, thereby exerting the DNA damaging properties as parts of the cytotoxic mechanisms.