Structure, chemistry and pharmacology of naphthoflavones

Naphthoflavones are synthetic flavonoids containing a conjugated phenyl group attached to A-ring of flavones. Most of their synthetic studies involved the Baker-Venkataraman rearrangement and subsequent cyclization catalyzed by acid. Based on their special structural features, these synthetic flavones exert pronounced influences on the metabolism of various endogenous and exogenous substances as well as the bioactivation of certain procarcinogens. Several mechanisms of these effects have been established, including the potent inhibition on CYP1 and aromatase, allosteric activation of CYP3A4 and/or activation of AhR. Furthermore, they have also been identified as CFTR activators, BCRP inhibitors and/or anticancer agents. All of the findings suggest that these synthetic ones are a series of promising lead compounds in cystic fibrosis therapeutic and anticancer drug discovery. This review primarily focuses on the structure, chemistry and pharmacology of naphthoflavones, while benzothioflavones, benzoflavanones, benzoflavans and benzochalcones as their analogues are also included.