Mikstacka Renata, Przybylska Dorota, Rimando Agnes M, Baer-Dubowska Wanda
Department of Pharmaceutical Biochemistry, University of Medical Sciences, Poznan, Poland.
Mol Nutr Food Res. 2007 May;51(5):517-24. doi: 10.1002/mnfr.200600135.
CYP1A1 and CYP1B1 are the inducible forms of cytochrome P450 expressed in extrahepatic tissues, which are responsible for the biotransformation of polycyclic aromatic hydrocarbons, heterocyclic amines and estradiol to the carcinogenic intermediates. The aim of our research was to determine and compare the inhibitory effect of naturally occurring analogues of trans-resveratrol on the catalytic activities of human recombinant CYP1A1 and CYP1B1. Pinostilbene (3,4'-dihydroxy-5-methoxystilbene), desoxyrhapontigenin (3,5-dihydroxy-4'-methoxystilbene), and pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) appeared to be very potent inhibitors of CYP1A1 catalytic activity with Ki values of 0.13, 0.16 and 0.57 microM, respectively. Results from this study indicate that trans-resveratrol analogues in which the hydroxy groups are substituted by methoxy groups exhibit a remarkably stronger inhibitory effect towards CYP1A1 in comparison to the parent compound. On the contrary, the potency of pinostilbene, desoxyrhapontigenin and pterostilbene towards CYP1B1 with Ki values of 0.90, 2.06 and 0.91 microM, respectively, was comparable to that of resveratrol. It appears that between these analogues, inhibition of CYP1A1 and CYP1B1 catalytic activities does not vary much regardless of the number and position of methylether substitution. The results suggest that the trans-resveratrol analogues: pinostilbene, desoxyrhapontigenin and pterostilbene, which occur in some food plants, might be considered as promising chemopreventive agents.
细胞色素P450的诱导型CYP1A1和CYP1B1在肝外组织中表达，负责将多环芳烃、杂环胺和雌二醇生物转化为致癌中间体。我们研究的目的是测定并比较反式白藜芦醇天然类似物对人重组CYP1A1和CYP1B1催化活性的抑制作用。白皮杉醇（3,4'-二羟基-5-甲氧基芪）、去氧rhapontigenin（3,5-二羟基-4'-甲氧基芪）和紫檀芪（3,5-二甲氧基-4'-羟基芪）似乎是CYP1A1催化活性的非常有效的抑制剂，其Ki值分别为0.13、0.16和0.57微摩尔。这项研究的结果表明，羟基被甲氧基取代的反式白藜芦醇类似物与母体化合物相比，对CYP1A1表现出明显更强的抑制作用。相反，白皮杉醇、去氧rhapontigenin和紫檀芪对CYP1B1的效力，其Ki值分别为0.90、2.06和0.91微摩尔，与白藜芦醇相当。在这些类似物之间，无论甲基醚取代的数量和位置如何，对CYP1A1和CYP1B1催化活性的抑制作用变化不大。结果表明，存在于一些食用植物中的反式白藜芦醇类似物：白皮杉醇、去氧rhapontigenin和紫檀芪，可能被认为是有前景的化学预防剂。
