Noduliprevenone: a novel heterodimeric chromanone with cancer chemopreventive potential.

Chemoprevention is considered a new strategy in fighting diverse types of cancer. To influence cancer development and progression, signaling pathways, for example, enzymes like cyclooxygenase-2, transcription factors like NF-kB, and several metabolic processes leading to activation or deactivation of carcinogenic agents, are envisaged as promising approaches. Cytochrome P450 (CYP) enzymes activate xenobiotics and thus contribute to the generation of potent carcinogens. Accordingly, inhibition of cytochrome P450 isoforms, such as CYP1A enzymes, which play an important role in polycyclic aromatic hydrocarbon (PAH) induced cancer forms, is advantageous for chemoprevention. In contrast, the induction of phase II enzymes inactivates carcinogens and accelerates their renal or biliar elimination, forming conjugates with polar ligands, such as glutathione, glucuronic acid, and acetic or sulfuric acid. NAD(P)H:quinone reductase (QR) contributes in detoxification by catalysing the two-electronaccepted reduction of quinones to their corresponding, lowmutagenic hydroquinones and is therefore often used as biomarker. Accordingly, the aim of cancer chemopreventive strategy can include the inhibition of phase I enzymes accompanied with an increased phase II metabolism. The fungus Nodulisporium sp. is an endophyte of a Mediterranean alga, and produces the novel polyketide noduliprevenone (1), an unprecedented structure consisting of two