Design, Synthesis, and Discovery of Novel trans-Stilbene Analogues as Potent and Selective Human Cytochrome P450 1B1 Inhibitors

Citations Over TimeTop 10% of 2001 papers

Abstract

A series of trans-stilbene derivatives containing a 3,5-dimethoxyphenyl moiety were prepared through a new efficient solution phase synthetic pathway, and their inhibitory activities were evaluated on human cytochrome P450s (CYP) 1A1, 1A2, and 1B1 to find a potent and selective CYP1B1 inhibitor. We found that a substituent at the 2-position of the stilbene skeleton plays a very important role in discriminating between CYP1As and CYP1B1. Among the compounds tested, the most selective and potent CYP1B1 inhibitor was 2,3',4,5'-tetramethoxystilbene. Compound 7j, 2-[2-(3,5-dimethoxy-phenyl)vinyl]thiophene, showed greater inhibitory activities but had a lower selectivity toward all of the CYP1s tested.

Related Papers

• → METABOLISM OF RETINOIDS AND ARACHIDONIC ACID BY HUMAN AND MOUSE CYTOCHROME P450 1B1(2004)190 cited
• → Expression of CYP1A1 and CYP1B1 depends on cell-specific factors in human breast cancer cell lines: role of estrogen receptor status(1999)78 cited
• → Synthesis and structure-activity relationship studies of α-naphthoflavone derivatives as CYP1B1 inhibitors(2019)36 cited
• → Potent inhibition of carcinogen-bioactivating cytochrome P450 1B1 by the p53 inhibitor pifithrin α(2005)35 cited
• → Synthesis and SAR studies of a novel class of S1P1 receptor antagonists(2007)14 cited