α-Naphthoflavone

α-Naphthoflavone (α-NF), also known as 7,8-benzoflavone and 2-phenyl-benzo(h)chromen-4-one, is a synthetic flavone derivative. α-Naphthoflavone is a potent inhibitor of the enzyme aromatase, which implicated in converting testosterone to estrogen [1]. It can be prepared from 2-naphthol and cinnamaldehyde [2]. α-naphthoflavone functions as both an Ah receptor antagonist and an inhibitor of cytochrome P450 activity. α-naphthoflavone stimulated P450 3A4 by selectively binding and activating an otherwise inactive subpopulation of this P450 and promoting benzo[a]pyrene binding to the latter [3].

In vitro: α-NF inhibited microsomal rabbit CYP3A6 and human CYP3A4 irreversibly. α-NF and β-NF strongly inhibited CYP1A-mediated ethoxyresorufin O-deethylase (EROD) activity with the Ki value of 9.1 ± 0.8 and 7.6 ± 1.1 nM, respectively. α-NF at 0.5, 5, 50 and 500 μM inhibited liver microsome-catalyzed AFB1-DNA binding by 22, 58, 84 and 91%, respectively [4].

In vivo: α-NF inhibited CYP1A enzymes and caused both synergism and antagonism of retene toxicity to rainbow trout (Oncorhynchus mykiss) [5]. In male Sprague–Dawley rats, treatment with αNF had no significant effects on body mass after 5 days and caused only minor increases of liver, kidney, and heart CYP1A1 mRNA. In contrast, lung CYP1A1 mRNA was increased by αNF treatment to levels comparable to that seen with β-NF treatment [6].

References:
[1].  Campbell D R, Kurzer M S. Flavonoid inhibition of aromatase enzyme activity in human preadipocytes[J]. The Journal of steroid biochemistry and molecular biology, 1993, 46(3): 381-388.
[2].  Harvey R G, HAHN J T A I, Bukowska M, et al. A new chromone and flavone synthesis and its utilization for the synthesis of potentially antitumorigenic polycyclic chromones and flavones[J]. Journal of organic chemistry, 1990, 55(25): 6161-6166.
[3].  Koley A P, Buters J T M, Robinson R C, et al. Differential mechanisms of cytochrome P450 inhibition and activation by α-naphthoflavone[J]. Journal of Biological Chemistry, 1997, 272(6): 3149-3152.
[4].  Takahashi N, Miranda C L, Henderson M C, et al. Inhibition of in vitro aflatoxin B1-DNA binding in rainbow trout by CYP1A inhibitors: α-naphthoflavone, β-naphthoflavone and trout CYP1A1 peptide antibody[J]. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 1995, 110(3): 273-280.
[5].  Hodson P V, Qureshi K, Noble C A J, et al. Inhibition of CYP1A enzymes by α-naphthoflavone causes both synergism and antagonism of retene toxicity to rainbow trout (Oncorhynchus mykiss)[J]. Aquatic toxicology, 2007, 81(3): 275-285.
[6].  Sinal C J, Webb C D, Bend J R. Differential in vivo effects of α‐naphthoflavone and β‐naphthoflavone on CYP1A1 and CYP2E1 in rat liver, lung, heart, and kidney[J]. Journal of biochemical and molecular toxicology, 1999, 13(1): 29-40.